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Sample records for altered hippocampal volume

  1. HLA-A2 Alleles Mediate Alzheimer's Disease by Altering Hippocampal Volume.

    Science.gov (United States)

    Wang, Zi-Xuan; Wang, Hui-Fu; Tan, Lin; Sun, Fu-Rong; Tan, Meng-Shan; Tan, Chen-Chen; Jiang, Teng; Tan, Lan; Yu, Jin-Tai

    2017-05-01

    HLA-A is a locus of the major histocompatibility complex situated on chromosome 6p21.3. HLA-A has been shown to be associated with susceptibility to Alzheimer's disease (AD). In this study, we firstly investigated the association of gene variants in HLA-A and brain structures on MRI in a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to explore the effects of HLA-A on AD pathogenesis. We selected the hippocampus, parahippocampus, posterior cingulate, precuneus, middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). In hybrid population analysis, our results showed a marginally significant association between rs9260168 and the atrophy of the left parahippocampus (P = 0.007, Pc = 0.054), rs3823342 and the atrophy of the left parahippocampus (P = 0.014, Pc = 0.054), rs76475517, which only exists in Caucasians with HLA-A23 or HLA-A24 alleles, and the atrophy of the right amygdala (P = 0.010, Pc = 0.085) at baseline. In particular, the haplotype (TGACAAGG), as a surrogate marker of HLA-A2, was founded to be positively associated with the atrophy of the right hippocampus (P = 0.047) at baseline. Furthermore, we detected the above four associations in mild cognitive impairment (MCI) subpopulation analysis. Our study provided preliminary evidences supporting HLA-A2 in Caucasians contribute to the risk of AD by modulating the alteration of hippocampal volume and HLA-A gene variants appear to play a role in altering AD-related brain structures on MRI.

  2. A longitudinal study of alterations of hippocampal volumes and serum BDNF levels in association to atypical antipsychotics in a sample of first-episode patients with schizophrenia.

    Directory of Open Access Journals (Sweden)

    Emmanouil Rizos

    Full Text Available BACKGROUND: Schizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels. METHODS: In the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP. MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs. RESULTS: We found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024. CONCLUSIONS: The association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies.

  3. Early maternal alcohol consumption alters hippocampal DNA methylation, gene expression and volume in a mouse model.

    Directory of Open Access Journals (Sweden)

    Heidi Marjonen

    Full Text Available The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v ethanol for the first 8 days of gestation (GD 0.5-8.5. Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60: we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in

  4. Comparison of Hippocampal Volume in Dementia Subtypes

    International Nuclear Information System (INIS)

    Vijayakumar, Avinash; Vijayakumar, Abhishek

    2012-01-01

    Aims. To examine the relationship between different types of dementia and hippocampal volume. Methods. Hippocampal volume was measured using FL3D sequence magnetic resonance imaging in 26 Alzheimer's, vascular dementia, mixed dementia, and normal pressure hydrocephalus patients and 15 healthy controls and also hippocampal ratio, analyzed. Minimental scale was used to stratify patients on cognitive function impairments. Results. Hippocampal volume and ratio was reduced by 25% in Alzheimer's disease, 21% in mixed dementia, 11% in vascular dementia and 5% in normal pressure hydrocephalus in comparison to control. Also an asymmetrical decrease in volume of left hippocampus was noted. The severity of dementia increased in accordance to decreasing hippocampal volume. Conclusion. Measurement in hippocampal volume may facilitate in differentiating different types of dementia and in disease progression. There was a correlation between hippocampal volume and severity of cognitive impairment

  5. Novel genetic loci associated with hippocampal volume

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); H.H.H. Adams (Hieab); N. Jahanshad (Neda); G. Chauhan (Ganesh); J.L. Stein; E. Hofer (Edith); M.E. Rentería (Miguel); J.C. Bis (Joshua); A. Arias-Vásquez (Alejandro); Ikram, M.K. (M. Kamran); S. Desrivières (Sylvane); M.W. Vernooij (Meike); L. Abramovic (Lucija); S. Alhusaini (Saud); N. Amin (Najaf); M. Andersson (Micael); K. Arfanakis (Konstantinos); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); L. Athanasiu (Lavinia); T. Axelsson (Tomas); A.H. Beecham (Ashley); A. Beiser (Alexa); M. Bernard (Manon); S.H. Blanton (Susan H.); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.M. Brickman (Adam M.); Carmichael, O. (Owen); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); V. Chouraki (Vincent); G. Cuellar-Partida (Gabriel); F. Crivello (Fabrice); A. den Braber (Anouk); Doan, N.T. (Nhat Trung); S.M. Ehrlich (Stefan); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); R.F. Gottesman (Rebecca); O. Grimm (Oliver); M.D. Griswold (Michael); T. Guadalupe (Tulio); Gutman, B.A. (Boris A.); J. Hass (Johanna); U.K. Haukvik (Unn); D. Hoehn (David); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); Jørgensen, K.N. (Kjetil N.); N. Karbalai (Nazanin); D. Kasperaviciute (Dalia); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil); D.C. Liewald (David C.); L.M. Lopez (Lorna); M. Luciano (Michelle); C. MacAre (Christine); Marquand, A.F. (Andre F.); M. Matarin (Mar); R. Mather; M. Mattheisen (Manuel); McKay, D.R. (David R.); Milaneschi, Y. (Yuri); S. Muñoz Maniega (Susana); K. Nho (Kwangsik); A.C. Nugent (Allison); P. Nyquist (Paul); Loohuis, L.M.O. (Loes M. Olde); J. Oosterlaan (Jaap); M. Papmeyer (Martina); Pirpamer, L. (Lukas); B. Pütz (Benno); A. Ramasamy (Adaikalavan); Richards, J.S. (Jennifer S.); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); N. Rommelse (Nanda); S. Ropele (Stefan); E.J. Rose (Emma); N.A. Royle (Natalie); T. Rundek (Tatjana); P.G. Sämann (Philipp); Saremi, A. (Arvin); C.L. Satizabal (Claudia L.); L. Schmaal (Lianne); N.J. Schork (Nicholas); Shen, L. (Li); J. Shin (Jean); Shumskaya, E. (Elena); A.V. Smith (Albert Vernon); R. Sprooten (Roy); V.M. Strike (Vanessa); A. Teumer (Alexander); D. Tordesillas-Gutierrez (Diana); R. Toro (Roberto); D. Trabzuni (Danyah); S. Trompet (Stella); D. Vaidya (Dhananjay); J. van der Grond (Jeroen); S.J. van der Lee (Sven); Van Der Meer, D. (Dennis); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); T.G.M. van Erp (Theo G.); Van Rooij, D. (Daan); E. Walton (Esther); L.T. Westlye (Lars); C.D. Whelan (Christopher); B.G. Windham (B Gwen); A.M. Winkler (Anderson); K. Wittfeld (Katharina); G. Woldehawariat (Girma); A. Björnsson (Asgeir); Wolfers, T. (Thomas); L.R. Yanek (Lisa); Yang, J. (Jingyun); A.P. Zijdenbos; M.P. Zwiers (Marcel); I. Agartz (Ingrid); L. Almasy (Laura); D.J. Ames (David); Amouyel, P. (Philippe); O.A. Andreassen (Ole); S. Arepalli (Sampath); A.A. Assareh; S. Barral (Sandra); M.E. Bastin (Mark); Becker, D.M. (Diane M.); J.T. Becker (James); D.A. Bennett (David A.); J. Blangero (John); H. van Bokhoven (Hans); D.I. Boomsma (Dorret); H. Brodaty (Henry); R.M. Brouwer (Rachel); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan); K. Bulayeva (Kazima); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); D.M. Cannon (Dara); G. Cavalleri (Gianpiero); Cheng, C.-Y. (Ching-Yu); S. Cichon (Sven); M.R. Cookson (Mark); A. Corvin (Aiden); B. Crespo-Facorro (Benedicto); J.E. Curran (Joanne); M. Czisch (Michael); A.M. Dale (Anders); G.E. Davies (Gareth); A.J. de Craen (Anton); E.J.C. de Geus (Eco); P.L. de Jager (Philip); G.I. de Zubicaray (Greig); I.J. Deary (Ian J.); S. Debette (Stéphanie); C. DeCarli (Charles); N. Delanty; C. Depondt (Chantal); A.L. DeStefano (Anita); A. Dillman (Allissa); S. Djurovic (Srdjan); D.J. Donohoe (Dennis); D.A. Drevets (Douglas); Duggirala, R. (Ravi); M.D. Dyer (Matthew); C. Enzinger (Christian); S. Erk; T. Espeseth (Thomas); Fedko, I.O. (Iryna O.); Fernández, G. (Guillén); L. Ferrucci (Luigi); S.E. Fisher (Simon); D. Fleischman (Debra); I. Ford (Ian); M. Fornage (Myriam); T. Foroud (Tatiana); P.T. Fox (Peter); C. Francks (Clyde); Fukunaga, M. (Masaki); Gibbs, J.R. (J. Raphael); D.C. Glahn (David); R.L. Gollub (Randy); H.H.H. Göring (Harald H.); R.C. Green (Robert C.); O. Gruber (Oliver); V. Gudnason (Vilmundur); S. Guelfi (Sebastian); Håberg, A.K. (Asta K.); N.K. Hansell (Narelle); J. Hardy (John); C.A. Hartman (C.); Hashimoto, R. (Ryota); K. Hegenscheid (Katrin); J. Heinz (Judith); S. Le Hellard (Stephanie); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); Ho, B.-C. (Beng-Choon); P.J. Hoekstra (Pieter); W. Hoffmann (Wolfgang); A. Hofman (Albert); F. Holsboer (Florian); G. Homuth (Georg); N. Hosten (Norbert); J.J. Hottenga (Jouke Jan); M.J. Huentelman (Matthew); H.H. Pol; Ikeda, M. (Masashi); Jack, C.R. (Clifford R.); S. Jenkinson (Sarah); R. Johnson (Robert); Jönsson, E.G. (Erik G.); J.W. Jukema; R. Kahn (René); Kanai, R. (Ryota); I. Kloszewska (Iwona); Knopman, D.S. (David S.); P. Kochunov (Peter); Kwok, J.B. (John B.); S. Lawrie (Stephen); H. Lemaître (Herve); X. Liu (Xinmin); D.L. Longo (Dan L.); O.L. Lopez (Oscar L.); S. Lovestone (Simon); Martinez, O. (Oliver); J.-L. Martinot (Jean-Luc); V.S. Mattay (Venkata S.); McDonald, C. (Colm); A.M. McIntosh (Andrew); McMahon, F.J. (Francis J.); McMahon, K.L. (Katie L.); P. Mecocci (Patrizia); I. Melle (Ingrid); Meyer-Lindenberg, A. (Andreas); S. Mohnke (Sebastian); Montgomery, G.W. (Grant W.); D.W. Morris (Derek W); T.H. Mosley (Thomas H.); T.W. Mühleisen (Thomas); B. Müller-Myhsok (B.); M.A. Nalls (Michael); M. Nauck (Matthias); T.E. Nichols (Thomas); W.J. Niessen (Wiro); M.M. Nöthen (Markus); L. Nyberg (Lars); Ohi, K. (Kazutaka); R.L. Olvera (Rene); R.A. Ophoff (Roel); M. Pandolfo (Massimo); T. Paus (Tomas); Z. Pausova (Zdenka); B.W.J.H. Penninx (Brenda); Pike, G.B. (G. Bruce); S.G. Potkin (Steven); B.M. Psaty (Bruce); S. Reppermund; M. Rietschel (Marcella); J.L. Roffman (Joshua); N. Seiferth (Nina); J.I. Rotter (Jerome I.); M. Ryten (Mina); Sacco, R.L. (Ralph L.); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); R. Schmidt (Reinhold); Schmidt, H. (Helena); C.J. Schofield (Christopher); Sigursson, S. (Sigurdur); Simmons, A. (Andrew); A. Singleton (Andrew); S.M. Sisodiya (Sanjay); Smith, C. (Colin); J.W. Smoller; H. Soininen (H.); V.M. Steen (Vidar); D.J. Stott (David J.); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); M. Tsolaki (Magda); C. Tzourio (Christophe); A.G. Uitterlinden (André); Hernández, M.C.V. (Maria C. Valdés); M.P. van der Brug (Marcel); A. van der Lugt (Aad); N.J. van der Wee (Nic); N.E.M. van Haren (Neeltje E.); D. van 't Ent (Dennis); M.J.D. van Tol (Marie-José); B.N. Vardarajan (Badri); B. Vellas (Bruno); D.J. Veltman (Dick); H. Völzke (Henry); H.J. Walter (Henrik); J. Wardlaw (Joanna); A.M.J. Wassink (Annemarie); M.E. Weale (Michael); Weinberger, D.R. (Daniel R.); Weiner, M.W. (Michael W.); Wen, W. (Wei); E. Westman (Eric); T.J.H. White (Tonya); Wong, T.Y. (Tien Y.); Wright, C.B. (Clinton B.); R.H. Zielke (Ronald H.); A.B. Zonderman; N.G. Martin (Nicholas); C.M. van Duijn (Cornelia); M.J. Wright (Margaret); W.T. Longstreth Jr; G. Schumann (Gunter); H.J. Grabe (Hans Jörgen); B. Franke (Barbara); L.J. Launer (Lenore); S.E. Medland (Sarah Elizabeth); S. Seshadri (Sudha); P.M. Thompson (Paul); M.K. Ikram (Kamran)

    2017-01-01

    textabstractThe hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic

  6. Novel genetic loci associated with hippocampal volume

    NARCIS (Netherlands)

    Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivières, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S.; Armstrong, Nicola J.; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H.; Beiser, Alexa; Bernard, Manon; Blanton, Susan H.; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brickman, Adam M.; Carmichael, Owen; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L.; Gottesman, Rebecca F.; Grimm, Oliver; Griswold, Michael E.; Guadalupe, Tulio; Gutman, Boris A.; Hass, Johanna; Haukvik, Unn K.; Hoehn, David; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N.; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Liewald, David C. M.; Lopez, Lorna M.; Luciano, Michelle; Macare, Christine; Marquand, Andre F.; Matarin, Mar; Mather, Karen A.; Mattheisen, Manuel; McKay, David R.; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M. Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, Philipp G.; Saremi, Arvin; Satizabal, Claudia L.; Schmaal, Lianne; Schork, Andrew J.; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V.; Sprooten, Emma; Strike, Lachlan T.; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; van der Grond, Jeroen; van der Lee, Sven J.; van der Meer, Dennis; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; van Erp, Theo G. M.; van Rooij, Daan; Walton, Esther; Westlye, Lars T.; Whelan, Christopher D.; Windham, Beverly G.; Winkler, Anderson M.; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R.; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P.; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arepalli, Sampath; Assareh, Amelia A.; Barral, Sandra; Bastin, Mark E.; Becker, Diane M.; Becker, James T.; Bennett, David A.; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cahn, Wiepke; Calhoun, Vince D.; Cannon, Dara M.; Cavalleri, Gianpiero L.; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R.; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E.; Czisch, Michael; Dale, Anders M.; Davies, Gareth E.; de Craen, Anton J. M.; de Geus, Eco J. C.; de Jager, Philip L.; de Zubicaray, Greig I.; Deary, Ian J.; Debette, Stéphanie; Decarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C.; Duggirala, Ravi; Dyer, Thomas D.; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O.; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E.; Fleischman, Debra A.; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M.; Fox, Peter T.; Francks, Clyde; Fukunaga, Masaki; Gibbs, J. Raphael; Glahn, David C.; Gollub, Randy L.; Göring, Harald H. H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K.; Hansell, Narelle K.; Hardy, John; Hartman, Catharina A.; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G.; Heslenfeld, Dirk J.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L.; Lopez, Oscar L.; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W.; Morris, Derek W.; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L.; Ophoff, Roel A.; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W. J. H.; Pike, G. Bruce; Potkin, Steven G.; Psaty, Bruce M.; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L.; Romanczuk-Seiferth, Nina; Rotter, Jerome I.; Ryten, Mina; Sacco, Ralph L.; Sachdev, Perminder S.; Saykin, Andrew J.; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R.; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M.; Smith, Colin; Smoller, Jordan W.; Soininen, Hilkka; Steen, Vidar M.; Stott, David J.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G.; Hernández, Maria C. Valdés; van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J. A.; van Haren, Neeltje E. M.; van 't Ent, Dennis; van Tol, Marie-Jose; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y.; Wright, Clinton B.; Zielke, Ronald H.; Zonderman, Alan B.; Martin, Nicholas G.; van Duijn, Cornelia M.; Wright, Margaret J.; Longstreth, W. T.; Schumann, Gunter; Grabe, Hans J.; Franke, Barbara; Launer, Lenore J.; Medland, Sarah E.; Seshadri, Sudha; Thompson, Paul M.; Ikram, M. Arfan

    2017-01-01

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of

  7. Altered hippocampal volume and functional connectivity in males with Internet gaming disorder comparing to those with alcohol use disorder.

    Science.gov (United States)

    Yoon, Eun Jin; Choi, Jung-Seok; Kim, Heejung; Sohn, Bo Kyung; Jung, Hee Yeon; Lee, Jun-Young; Kim, Dai-Jin; Park, Sun-Won; Kim, Yu Kyeong

    2017-07-18

    Internet gaming disorder (IGD) has been conceptualized as a behavioral addiction and shares clinical, neuropsychological, and personality characteristics with alcohol use disorder (AUD), but IGD dose not entail brain exposure to toxic agents, which renders it different from AUD. To achieve a clear understanding of the neurobiological features of IGD, we aimed to identify morphological and functional changes in IGD and compare them with those in AUD. Individuals with IGD showed larger volume in the hippocampus/amygdala and precuneus than healthy controls (HCs). The volume in the hippocampus positively correlated with the symptom severity of IGD. Moreover, functional connectivity analysis with the hippocampus/amygdala cluster revealed that the left ventromedial prefrontal cortex showed stronger functional connectivity in individuals with IGD compared to those with AUD. In contrast, individuals with AUD exhibited the smaller cerebellar volume and thinner medial frontal cortex than HCs. The volume in the cerebellum correlated with impaired working memory function as well as duration of illness in AUD group. Findings suggested that altered volume and functional connectivity in the hippocampus/amygdala in IGD might be associated with abnormally enhanced memory process of gaming-related cues, while abnormal cortical changes and cognitive impairments in AUD might be associated with neurotoxic effects of alcohol.

  8. Novel genetic loci associated with hippocampal volume

    OpenAIRE

    Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivieres, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf

    2017-01-01

    International audience; The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal ...

  9. Novel genetic loci associated with hippocampal volume.

    Science.gov (United States)

    Hibar, Derrek P; Adams, Hieab H H; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L; Hofer, Edith; Renteria, Miguel E; Bis, Joshua C; Arias-Vasquez, Alejandro; Ikram, M Kamran; Desrivières, Sylvane; Vernooij, Meike W; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H; Beiser, Alexa; Bernard, Manon; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Gutman, Boris A; Hass, Johanna; Haukvik, Unn K; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre F; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; McKay, David R; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C; Nyquist, Paul; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Saremi, Arvin; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Craen, Anton J M; De Geus, Eco J C; De Jager, Philip L; De Zubicaray, Greig I; Deary, Ian J; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J A; Van Haren, Neeltje E M; van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Vellas, Bruno; Veltman, Dick J; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, Ronald H; Zonderman, Alan B; Martin, Nicholas G; Van Duijn, Cornelia M; Wright, Margaret J; Longstreth, W T; Schumann, Gunter; Grabe, Hans J; Franke, Barbara; Launer, Lenore J; Medland, Sarah E; Seshadri, Sudha; Thompson, Paul M; Ikram, M Arfan

    2017-01-18

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r g =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

  10. Altered Hippocampal Morphology in Unmedicated Patients with Major Depressive Illness

    Directory of Open Access Journals (Sweden)

    Carrie E Bearden

    2009-10-01

    Full Text Available Despite converging evidence that major depressive illness is associated with both memory impairment and hippocampal pathology, findings vary widely across studies and it is not known whether these changes are regionally specific. In the present study we acquired brain MRIs (magnetic resonance images from 31 unmedicated patients with MDD (major depressive disorder; mean age 39.2±11.9 years; 77% female and 31 demographically comparable controls. Three-dimensional parametric mesh models were created to examine localized alterations of hippocampal morphology. Although global volumes did not differ between groups, statistical mapping results revealed that in MDD patients, more severe depressive symptoms were associated with greater left hippocampal atrophy, particularly in CA1 (cornu ammonis 1 subfields and the subiculum. However, previous treatment with atypical antipsychotics was associated with a trend towards larger left hippocampal volume. Our findings suggest effects of illness severity on hippocampal size, as well as a possible effect of past history of atypical antipsychotic treatment, which may reflect prolonged neuroprotective effects. This possibility awaits confirmation in longitudinal studies.

  11. Can Molecular Hippocampal Alterations Explain Behavioral ...

    Science.gov (United States)

    Studies in both humans and animals have shown that prenatal stress can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined genotypical outcomes in adult male and female offspring of rats exposed to variable stress during pregnancy. Dams (n=15/treatment) were subjected to several non-chemical stressors including intermittent noise, light, crowding, restraint, and altered circadian lighting, from gestational day (GD) 13 to 20. Tail blood was drawn on GD 12, 16 and 20 to verify a stress response. Corticosterone levels were not different between the stressed and non-stressed dams on GD12 but was significantly increased in stressed dams on GD 16 and 20 compared to controls. Dams gave birth on GD22 (postnatal day or PND 0). Several behavioral tests were used to assess the cognitive and behavioral phenotype of the offspring from PND 49 through 86, including the Morris water maze and novel object recognition. Male and female stressed offspring showed reduced reversal learning on the Morris water maze and stressed females did not show a significant preference for the novel object (57 ± 8%) while control females did (71 ± 3%). This indicates altered cognition in prenatally stressed offspring. On PND 91-92, offspring were necropsied and hippocampal tissue was collected. Genotypic outcomes of prenatal stress w

  12. Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

    Science.gov (United States)

    Henje Blom, E; Han, L K M; Connolly, C G; Ho, T C; Lin, J; LeWinn, K Z; Simmons, A N; Sacchet, M D; Mobayed, N; Luna, M E; Paulus, M; Epel, E S; Blackburn, E H; Wolkowitz, O M; Yang, T T

    2015-11-10

    Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

  13. Hippocampal volume and cognitive function in anorexia nervosa.

    Science.gov (United States)

    Connan, Frances; Murphy, Fay; Connor, Steve E J; Rich, Phil; Murphy, Tara; Bara-Carill, Nuria; Landau, Sabine; Krljes, Sanya; Ng, Virginia; Williams, Steve; Morris, Robin G; Campbell, Iain C; Treasure, Janet

    2006-03-31

    We hypothesised that hippocampal volume would be reduced in underweight anorexia nervosa (AN) and associated with impaired hippocampus-dependent cognitive function. Hippocampal and whole brain volumes were measured in 16 women with AN and 16 matched healthy women using magnetic resonance imaging (MRI) and a manual tracing method. Participants also completed the Doors and People Test of hippocampus-dependent memory and an IQ test. After adjustment for total cerebral volume, there was significant bilateral reduction in hippocampal volume in the AN group (8.2% right; 7.5% left). There was no evidence of impaired hippocampus-dependent cognitive function and no evidence of a relationship between hippocampal volume and clinical features of AN. The reduced hippocampal volume in anorexia nervosa is not associated with changes in cognitive function. To understand the cause and consequence of hippocampal size and function, it will be important to integrate endocrine, neuropsychological and neuroimaging studies.

  14. The role of hippocampal iron concentration and hippocampal volume in age-related differences in memory.

    Science.gov (United States)

    Rodrigue, Karen M; Daugherty, Ana M; Haacke, E Mark; Raz, Naftali

    2013-07-01

    The goal of this study was to examine the relationships between 2 age-sensitive indices of brain integrity--volume and iron concentration--and the associated age differences in memory performance. In 113 healthy adults (age 19-83 years), we measured the volume and estimated iron concentration in the hippocampus (HC), caudate nucleus (Cd), and primary visual cortex (VC) in vivo with T2* relaxation times, and assessed memory performance with multiple tests. We applied structural equation modeling to evaluate the contribution of individual differences in 2 indices of integrity, volume and T2*, to age-related memory variance. The results show that in healthy adults, age differences in memory can be explained in part by individual differences in HC volume that in turn are associated with differences in HC iron concentration. Lower memory scores were linked to smaller HC and higher HC iron concentration. No such associations were noted for Cd and VC. We conclude that the association between age-related declines in memory and reduced hippocampal volume may reflect the impact of oxidative stress related to increase in free iron concentration. Longitudinal follow-up is needed to test whether altered iron homeostasis in the HC is an early marker for age-related cognitive decline.

  15. Hippocampal and Amygdalar Volumes in Dissociative Identity Disorder

    Science.gov (United States)

    Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J.; Bremner, J. Douglas

    2011-01-01

    Objective Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. Method The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Results Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. Conclusions The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects. PMID:16585437

  16. Hippocampal and amygdalar volumes in dissociative identity disorder.

    Science.gov (United States)

    Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J; Bremner, J Douglas

    2006-04-01

    Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.

  17. An association between human hippocampal volume and topographical memory in healthy young adults.

    Science.gov (United States)

    Hartley, Tom; Harlow, Rachel

    2012-01-01

    The association between human hippocampal structure and topographical memory was investigated in healthy adults (N = 30). Structural MR images were acquired, and voxel-based morphometry (VBM) was used to estimate local gray matter volume throughout the brain. A complementary automated mesh-based segmentation approach was used to independently isolate and measure specified structures including the hippocampus. Topographical memory was assessed using a version of the Four Mountains Task, a short test designed to target hippocampal spatial function. Each item requires subjects to briefly study a landscape scene before recognizing the depicted place from a novel viewpoint and under altered non-spatial conditions when presented amongst similar alternative scenes. Positive correlations between topographical memory performance and hippocampal volume were observed in both VBM and segmentation-based analyses. Score on the topographical memory task was also correlated with the volume of some subcortical structures, extra-hippocampal gray matter, and total brain volume, with the most robust and extensive covariation seen in circumscribed neocortical regions in the insula and anterior temporal lobes. Taken together with earlier findings, the results suggest that global variations in brain morphology affect the volume of the hippocampus and its specific contribution to topographical memory. We speculate that behavioral variation might arise directly through the impact of resource constraints on spatial representations in the hippocampal formation and its inputs, and perhaps indirectly through an increased reliance on non-allocentric strategies.

  18. An association between human hippocampal volume and topographical memory in healthy young adults.

    Directory of Open Access Journals (Sweden)

    Tom eHartley

    2012-12-01

    Full Text Available The association between human hippocampal structure and topographical memory was investigated in healthy adults (N=30. Structural MR images were acquired, and voxel-based morphometry (VBM was used to estimate local gray matter volume throughout the brain. A complementary automated mesh-based segmentation approach was used to independently isolate and measure specified structures including the hippocampus. Topographical memory was assessed using a version of the Four Mountains Task, a short test designed to target hippocampal spatial function. Each item requires subjects to briefly study a landscape scene before recognizing the depicted place from a novel viewpoint and under altered non-spatial conditions when presented amongst similar alternative scenes. Positive correlations between topographical memory performance and hippocampal volume were observed in both VBM and segmentation-based analyses. Score on the topographical memory task was also correlated with the volume of some subcortical structures, extra-hippocampal gray matter and total brain volume, with the most robust and extensive covariation seen in circumscribed neocortical regions in the insula and anterior temporal lobes. Taken together with earlier findings, the results suggest that global variations in brain morphology affect the volume of the hippocampus and its specific contribution to topographical memory. We speculate that behavioral variation might arise directly through the impact of resource constraints on spatial representations in the hippocampal formation and its inputs, and perhaps indirectly through an increased reliance on non-allocentric strategies.

  19. Combined effects of marijuana and nicotine on memory performance and hippocampal volume.

    Science.gov (United States)

    Filbey, Francesca M; McQueeny, Tim; Kadamangudi, Shrinath; Bice, Collette; Ketcherside, Ariel

    2015-10-15

    Combined use of marijuana (MJ) and tobacco is highly prevalent in today's population. Individual use of either substance is linked to structural brain changes and altered cognitive function, especially with consistent reports of hippocampal volume deficits and poorer memory performance. However, the combined effects of MJ and tobacco on hippocampal structure and on learning and memory processes remain unknown. In this study, we examined both the individual and combined effects of MJ and tobacco on hippocampal volumes and memory performance in four groups of adults taken from two larger studies: MJ-only users (n=36), nicotine-only (Nic-only, n=19), combined marijuana and nicotine users (MJ+Nic, n=19) and non-using healthy controls (n=16). Total bilateral hippocampal volumes and memory performance (WMS-III logical memory) were compared across groups controlling for total brain size and recent alcohol use. Results found MJ and MJ+Nic groups had smaller total hippocampal volumes compared to Nic-only and controls. No significant difference between groups was found between immediate and delayed story recall. However, the controls showed a trend for larger hippocampal volumes being associated with better memory scores, while MJ+Nic users showed a unique inversion, whereby smaller hippocampal volume was associated with better memory. Overall, results suggest abnormalities in the brain-behavior relationships underlying memory processes with combined use of marijuana and nicotine use. Further research will need to address these complex interactions between MJ and nicotine. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  20. 3T MRI quantification of hippocampal volume and signal in mesial temporal lobe epilepsy improves detection of hippocampal sclerosis.

    Science.gov (United States)

    Coan, A C; Kubota, B; Bergo, F P G; Campos, B M; Cendes, F

    2014-01-01

    In mesial temporal lobe epilepsy, MR imaging quantification of hippocampal volume and T2 signal can improve the sensitivity for detecting hippocampal sclerosis. However, the current contributions of these analyses for the diagnosis of hippocampal sclerosis in 3T MRI are not clear. Our aim was to compare visual analysis, volumetry, and signal quantification of the hippocampus for detecting hippocampal sclerosis in 3T MRI. Two hundred three patients with mesial temporal lobe epilepsy defined by clinical and electroencephalogram criteria had 3T MRI visually analyzed by imaging epilepsy experts. As a second step, we performed automatic quantification of hippocampal volumes with FreeSurfer and T2 relaxometry with an in-house software. MRI of 79 healthy controls was used for comparison. Visual analysis classified 125 patients (62%) as having signs of hippocampal sclerosis and 78 (38%) as having normal MRI findings. Automatic volumetry detected atrophy in 119 (95%) patients with visually detected hippocampal sclerosis and in 10 (13%) with visually normal MR imaging findings. Relaxometry analysis detected hyperintense T2 signal in 103 (82%) patients with visually detected hippocampal sclerosis and in 15 (19%) with visually normal MR imaging findings. Considered together, volumetry plus relaxometry detected signs of hippocampal sclerosis in all except 1 (99%) patient with visually detected hippocampal sclerosis and in 22 (28%) with visually normal MR imaging findings. In 3T MRI visually inspected by experts, quantification of hippocampal volume and signal can increase the detection of hippocampal sclerosis in 28% of patients with mesial temporal lobe epilepsy.

  1. Hippocampal volume reduction in congenital central hypoventilation syndrome.

    Directory of Open Access Journals (Sweden)

    Paul M Macey

    Full Text Available Children with congenital central hypoventilation syndrome (CCHS, a genetic disorder characterized by diminished drive to breathe during sleep and impaired CO(2 sensitivity, show brain structural and functional changes on magnetic resonance imaging (MRI scans, with impaired responses in specific hippocampal regions, suggesting localized injury.We assessed total volume and regional variation in hippocampal surface morphology to identify areas affected in the syndrome. We studied 18 CCHS (mean age+/-std: 15.1+/-2.2 years; 8 female and 32 healthy control (age 15.2+/-2.4 years; 14 female children, and traced hippocampi on 1 mm(3 resolution T1-weighted scans, collected with a 3.0 Tesla MRI scanner. Regional hippocampal volume variations, adjusted for cranial volume, were compared between groups based on t-tests of surface distances to the structure midline, with correction for multiple comparisons. Significant tissue losses emerged in CCHS patients on the left side, with a trend for loss on the right; however, most areas affected on the left also showed equivalent right-sided volume reductions. Reduced regional volumes appeared in the left rostral hippocampus, bilateral areas in mid and mid-to-caudal regions, and a dorsal-caudal region, adjacent to the fimbria.The volume losses may result from hypoxic exposure following hypoventilation during sleep-disordered breathing, or from developmental or vascular consequences of genetic mutations in the syndrome. The sites of change overlap regions of abnormal functional responses to respiratory and autonomic challenges. Affected hippocampal areas have roles associated with memory, mood, and indirectly, autonomic regulation; impairments in these behavioral and physiological functions appear in CCHS.

  2. Photoperiod is associated with hippocampal volume in a large community sample.

    Science.gov (United States)

    Miller, Megan A; Leckie, Regina L; Donofry, Shannon D; Gianaros, Peter J; Erickson, Kirk I; Manuck, Stephen B; Roecklein, Kathryn A

    2015-04-01

    Although animal research has demonstrated seasonal changes in hippocampal volume, reflecting seasonal neuroplasticity, seasonal differences in human hippocampal volume have yet to be documented. Hippocampal volume has also been linked to depressed mood, a seasonally varying phenotype. Therefore, we hypothesized that seasonal differences in day-length (i.e., photoperiod) would predict differences in hippocampal volume, and that this association would be linked to low mood. Healthy participants aged 30-54 (M=43; SD=7.32) from the University of Pittsburgh Adult Health and Behavior II project (n=404; 53% female) were scanned in a 3T MRI scanner. Hippocampal volumes were determined using an automated segmentation algorithm using FreeSurfer. A mediation model tested whether hippocampal volume mediated the relationship between photoperiod and mood. Secondary analyses included seasonally fluctuating variables (i.e., sleep and physical activity) which have been shown to influence hippocampal volume. Shorter photoperiods were significantly associated with higher BDI scores (R(2)=0.01, β=-0.12, P=0.02) and smaller hippocampal volumes (R(2)=0.40, β=0.08, P=0.04). However, due to the lack of an association between hippocampal volume and Beck Depression Inventory scores in the current sample, the mediation hypothesis was not supported. This study is the first to demonstrate an association between season and hippocampal volume. These data offer preliminary evidence that human hippocampal plasticity could be associated with photoperiod and indicates a need for longitudinal studies. © 2014 Wiley Periodicals, Inc.

  3. Treadmill Exercise Induces Hippocampal Astroglial Alterations in Rats

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    Caren Bernardi

    2013-01-01

    Full Text Available Physical exercise effects on brain health and cognitive performance have been described. Synaptic remodeling in hippocampus induced by physical exercise has been described in animal models, but the underlying mechanisms remain poorly understood. Changes in astrocytes, the glial cells involved in synaptic remodeling, need more characterization. We investigated the effect of moderate treadmill exercise (20 min/day for 4 weeks on some parameters of astrocytic activity in rat hippocampal slices, namely, glial fibrillary acidic protein (GFAP, glutamate uptake and glutamine synthetase (GS activities, glutathione content, and S100B protein content and secretion, as well as brain-derived neurotrophic factor (BDNF levels and glucose uptake activity in this tissue. Results show that moderate treadmill exercise was able to induce a decrease in GFAP content (evaluated by ELISA and immunohistochemistry and an increase in GS activity. These changes could be mediated by corticosterone, whose levels were elevated in serum. BDNF, another putative mediator, was not altered in hippocampal tissue. Moreover, treadmill exercise caused a decrease in NO content. Our data indicate specific changes in astrocyte markers induced by physical exercise, the importance of studying astrocytes for understanding brain plasticity, as well as reinforce the relevance of physical exercise as a neuroprotective strategy.

  4. Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior.

    Science.gov (United States)

    Takada, Silvia Honda; Motta-Teixeira, Lívia Clemente; Machado-Nils, Aline Vilar; Lee, Vitor Yonamine; Sampaio, Carlos Alberto; Polli, Roberson Saraiva; Malheiros, Jackeline Moraes; Takase, Luiz Fernando; Kihara, Alexandre Hiroaki; Covolan, Luciene; Xavier, Gilberto Fernando; Nogueira, Maria Inês

    2016-01-01

    Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Spatial navigation impairment is proportional to right hippocampal volume

    Czech Academy of Sciences Publication Activity Database

    Nedelská, Z.; Andel, R.; Laczó, J.; Vlček, Kamil; Hořínek, D.; Lisý, J.; Sheardová, K.; Bureš, Jan; Hort, J.

    2012-01-01

    Roč. 109, č. 7 (2012), s. 2590-2594 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA309/09/1053; GA ČR(CZ) GA309/09/0286; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Grant - others:GA MZd(CZ) NS10331 Institutional research plan: CEZ:AV0Z50110509 Keywords : spatial navigation * Alzheimer’s Disease * hippocampal volume Subject RIV: FH - Neurology Impact factor: 9.737, year: 2012

  6. Hippocampal volume predicts fluid intelligence in musically trained people.

    Science.gov (United States)

    Oechslin, Mathias S; Descloux, Céline; Croquelois, Alexandre; Chanal, Julien; Van De Ville, Dimitri; Lazeyras, François; James, Clara E

    2013-07-01

    Recently, age-related hippocampal (HP) volume loss could be associated with a decrease in general fluid intelligence (gF). In the present study we investigated whether and how extensive musical training modulates human HP volume and gF performance. Previously, some studies demonstrated positive effects of musical training on higher cognitive functions such as learning and memory, associated with neural adaptations beyond the auditory domain. In order to detect possible associations between musical training and gF, we bilaterally segmented the HP formation and assessed the individual gF performance of people with different levels of musical expertise. Multiple regression analyses revealed that HP volume predicts gF in musicians but not in nonmusicians; in particular, bilaterally enhanced HP volume is associated with increased gF exclusively in musically trained people (amateurs and experts). This result suggests that musical training facilitates the recruitment of cognitive resources, which are essential for gF and linked to HP functioning. Musical training, even at a moderate level of intensity, can thus be considered as a potential strategy to decelerate age-related effects of cognitive decline. Copyright © 2013 Wiley Periodicals, Inc.

  7. Longitudinal changes in hippocampal volumes and cognition in remitted geriatric depressive disorder.

    Science.gov (United States)

    Hou, Zhenghua; Yuan, Yonggui; Zhang, Zhijun; Bai, Feng; Hou, Gang; You, Jiayong

    2012-02-01

    Growing evidences suggest that the abnormality of hippocampal volume may occur in the process of depression. In this longitudinal study, we calculated the hippocampal volume of 14 remitted geriatric depressed (RGD) patients and 19 healthy participants at baseline and follow-up. We found significant improvement of performance in Trail Making Test-A (P=0.038) and Test-B (P=0.032), and the right hippocampal volume increased mildly in RGD. However, in RGD patients, positive correlations were seen between the changes in right hippocampal volumes and Symbol Digit Modality Test scores (r=0.675, P=0.008), and changes in left hippocampal volumes and Mini-Mental State Examination scores (r=0.743, P=0.002). Our findings suggest that hippocampus related cognitive impairment and previously addressed decreased hippocampal volume might represent a state rather than a permanent trait of the depressive disorder. The results suggest that hippocampal volume may be a useful risk marker for conversion to Alzheimer's disease in RGD patients. Additionally, our study indicates that effective antidepressants treatment might postpone and even revise the deterioration of hippocampus to some degree. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Effect of Exercise Training on Hippocampal Volume in Humans: A Pilot Study

    Science.gov (United States)

    Parker, Beth A.; Thompson, Paul D.; Jordan, Kathryn C.; Grimaldi, Adam S.; Assaf, Michal; Jagannathan, Kanchana; Pearlson, Godfrey D.

    2011-01-01

    The hippocampus is the primary site of memory and learning in the brain. Both normal aging and various disease pathologies (e.g., alcoholism, schizophrenia, and major depressive disorder) are associated with lower hippocampal volumes in humans and hippocampal atrophy predicts progression of Alzheimers disease. In animals, there is convincing…

  9. The effect of exercise on hippocampal volume and neurotrophines in patients with major depression--a randomized clinical trial

    DEFF Research Database (Denmark)

    Krogh, Jesper; Rostrup, Egill; Thomsen, Carsten

    2014-01-01

    BACKGROUND: The hippocampal volume is reduced in patients with major depression. Exercise leads to an increased hippocampal volume in schizophrenia and in healthy old adults. The effect of exercise on hippocampal volume is potentially mediated by brain derived neurotrophic factor (BDNF), vascular...... endothelial growth factor (VEGF), and insulin like growth factor 1 (IGF-1). The aim of this trial was to assess the effect of an aerobic exercise intervention on hippocampal volume and serum BDNF, VEGF, and IGF-1 in patients with major depression. METHODS: Patients were randomized to an aerobic exercise.......2) in the control group (p=0.03). The hippocampal volume, BDNF, VEGF, or IGF-1 did not differ between the two groups. Post-hoc we found a positive association between change in hippocampal volume and verbal memory (Rho=0.27; p=0.05) and change in hippocampal volume and depressive symptoms (Rho=0.30; p=0...

  10. Association among clinical response, hippocampal volume, and FKBP5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy.

    Science.gov (United States)

    Levy-Gigi, Einat; Szabó, Csilla; Kelemen, Oguz; Kéri, Szabolcs

    2013-12-01

    Posttraumatic stress disorder (PTSD) is characterized by a reduced expression of FKBP5, a key modulator of the glucocorticoid receptor. Smaller hippocampal volume has also been documented in PTSD. We explored possible changes in FKBP5 gene expression and brain structure in patients with PTSD after cognitive behavioral therapy (CBT). We measured peripheral FKBP5 RNA and volumes of the hippocampus, amygdala, and medial orbitofrontal cortex in 39 patients with PTSD before and after CBT. The control subjects were 31 trauma-exposed individuals without PTSD who were also assessed twice. Gene expression changes were screened with a microarray toolkit, which was followed by quantitative polymerase chain reaction for FKBP5 RNA. Brain volumes were measured using FreeSurfer. At baseline, patients with PTSD showed lower FKBP5 gene expression and smaller hippocampal and medial orbitofrontal cortex, but not amygdala, volumes relative to control subjects. At follow-up, we found significantly increased FKBP5 expression and increased hippocampal volume in patients with PTSD. At follow-up, patients did not differ from control subjects in hippocampal volume. Improvement in PTSD symptoms was predicted by increased FKBP5 expression and increased hippocampal volume, but the primary predictor was FKBP5 expression. The most significantly altered gene expression in patients with PTSD relative to control subjects was found for ribosomal protein S6 kinase, which did not change after CBT and did not correlate with hippocampal volume. Clinical improvement in individuals with PTSD was associated with increased expression of FKBP5 and increased hippocampal volume, which were positively correlated. © 2013 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.

  11. Reading, writing, and reserve: Literacy activities are linked to hippocampal volume and memory in multiple sclerosis.

    Science.gov (United States)

    Sumowski, James F; Rocca, Maria A; Leavitt, Victoria M; Riccitelli, Gianna; Meani, Alessandro; Comi, Giancarlo; Filippi, Massimo

    2016-10-01

    Engagement in cognitive leisure activities during early adulthood has been linked to preserved memory and larger hippocampal volume in persons with multiple sclerosis (MS). To investigate which specific types of cognitive leisure activities contribute to hippocampal volume and memory. We investigated links between three types of cognitive activities (Reading-Writing, Art-Music, Games-Hobbies) and (a) hippocampal volume within independent samples of Italian (n=187) and American (n=55) MS patients and (b) memory in subsamples of Italian (n=97) and American (n=53) patients. Reading-Writing was the only predictor of hippocampal volume (rp=.204, p=.002), and the best predictor of memory (rp=.288, p=.001). Findings inform the development of targeted evidence-based enrichment programs aiming to bolster reserve against memory decline. © The Author(s), 2016.

  12. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease.

    Science.gov (United States)

    Dhikav, Vikas; Duraiswamy, Sharmila; Anand, Kuljeet Singh

    2017-01-01

    Hippocampus undergoes atrophy in patients with Alzheimer's disease (AD). Calculation of hippocampal volumes can be done by a variety of methods using T1-weighted images of magnetic resonance imaging (MRI) of the brain. Medial temporal lobes atrophy (MTL) can be rated visually using T1-weighted MRI brain images. The present study was done to see if any correlation existed between hippocampal volumes and visual rating scores of the MTL using Scheltens Visual Rating Method. We screened 84 subjects presented to the Department of Neurology of a Tertiary Care Hospital and enrolled forty subjects meeting the National Institute of Neurological and Communicative Disorders and Stroke, AD related Disease Association criteria. Selected patients underwent MRI brain and T1-weighted images in a plane perpendicular to long axis of hippocampus were obtained. Hippocampal volumes were calculated manually using a standard protocol. The calculated hippocampal volumes were correlated with Scheltens Visual Rating Method for Rating MTL. A total of 32 cognitively normal age-matched subjects were selected to see the same correlation in the healthy subjects as well. Sensitivity and specificity of both methods was calculated and compared. There was an insignificant correlation between the hippocampal volumes and MTL rating scores in cognitively normal elderly ( n = 32; Pearson Correlation coefficient = 0.16, P > 0.05). In the AD Group, there was a moderately strong correlation between measured hippocampal volumes and MTL Rating (Pearson's correlation coefficient = -0.54; P < 0.05. There was a moderately strong correlation between hippocampal volume and Mini-Mental Status Examination in the AD group. Manual delineation was superior compared to the visual method ( P < 0.05). Good correlation was present between manual hippocampal volume measurements and MTL scores. Sensitivity and specificity of manual measurement of hippocampus was higher compared to visual rating scores for MTL in patients

  13. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Vikas Dhikav

    2017-01-01

    Full Text Available Introduction: Hippocampus undergoes atrophy in patients with Alzheimer's disease (AD. Calculation of hippocampal volumes can be done by a variety of methods using T1-weighted images of magnetic resonance imaging (MRI of the brain. Medial temporal lobes atrophy (MTL can be rated visually using T1-weighted MRI brain images. The present study was done to see if any correlation existed between hippocampal volumes and visual rating scores of the MTL using Scheltens Visual Rating Method. Materials and Methods: We screened 84 subjects presented to the Department of Neurology of a Tertiary Care Hospital and enrolled forty subjects meeting the National Institute of Neurological and Communicative Disorders and Stroke, AD related Disease Association criteria. Selected patients underwent MRI brain and T1-weighted images in a plane perpendicular to long axis of hippocampus were obtained. Hippocampal volumes were calculated manually using a standard protocol. The calculated hippocampal volumes were correlated with Scheltens Visual Rating Method for Rating MTL. A total of 32 cognitively normal age-matched subjects were selected to see the same correlation in the healthy subjects as well. Sensitivity and specificity of both methods was calculated and compared. Results: There was an insignificant correlation between the hippocampal volumes and MTL rating scores in cognitively normal elderly (n = 32; Pearson Correlation coefficient = 0.16, P> 0.05. In the AD Group, there was a moderately strong correlation between measured hippocampal volumes and MTL Rating (Pearson's correlation coefficient = −0.54;P< 0.05. There was a moderately strong correlation between hippocampal volume and Mini-Mental Status Examination in the AD group. Manual delineation was superior compared to the visual method (P < 0.05. Conclusions: Good correlation was present between manual hippocampal volume measurements and MTL scores. Sensitivity and specificity of manual measurement of

  14. Hippocampal volume reduction in elderly patients at risk for postoperative cognitive dysfunction.

    Science.gov (United States)

    Chen, Ming-hua; Liao, Yan; Rong, Peng-fei; Hu, Rong; Lin, Guo-xin; Ouyang, Wen

    2013-08-01

    Postoperative cognitive dysfunction (POCD) is a formidable public health issue, which would not only affect the quality of life among elderly patients but also lead to pulmonary infection and increased mortality. While, there is a lack of an effective indicator in predicting POCD. As one pivotal part of the limbic system in brain, hippocampus is associated with cognitive function. Hippocampal atrophy could indicate the degree of changes in cognitive function. Forty-one ASA II or III patients (23 male, 18 female) aged ≥65 years undergoing open gastrointestinal tract surgery were enrolled in this study. MRI was performed to measure the volume of hippocampal formation before surgery and the results were standardized according to individual intracranial volume. All patients underwent a battery of neuropsychological tests including sensitive tests on the Wechsler adult memory scale and Wechsler adult intelligence scale, trail making test and the grooved pegboard test. We used the Z score to identify POCD as recommended by ISPOCD. All patients were then divided into POCD group and non-POCD group according to the results of the neuropsychological tests. The results of the tests were correlated with the volume of hippocampal formation measured by MRI. The value of MRI measurement of hippocampal volume in predicting POCD was analyzed. Multivariate linear correlation analyses of compositive Z score using potential contributing factors such as age, duration of anesthesia, education and hippocampal volume was carried out. Thirty-six patients completed the whole battery of neuropsychological tests after surgery. Thirteen of the 36 patients were found to have POCD (36 %) on the postoperative 4th day. The hippocampal volume was significantly smaller in POCD group (4.75 ± 0.23) than in non-POCD group (5.06 ± 0.31). Hippocampal volume had great influence on Z score, and had negative correlation with Z score. The MRI measurement of hippocampal volume is suggested to be valuable

  15. Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression.

    Science.gov (United States)

    Nordanskog, P; Larsson, M R; Larsson, E-M; Johanson, A

    2014-04-01

    In a previous magnetic resonance imaging (MRI) study, we found a significant increase in hippocampal volume immediately after electroconvulsive therapy (ECT) in patients with depression. The aim of this study was to evaluate hippocampal volume up to 1 year after ECT and investigate its possible relation to clinical and cognitive outcome. Clinical and cognitive outcome in 12 in-patients with depression receiving antidepressive pharmacological treatment referred for ECT were investigated with the Montgomery-Asberg Depression Rating Scale (MADRS) and a broad neuropsychological test battery within 1 week before and after ECT. The assessments were repeated 6 and 12 months after baseline in 10 and seven of these patients, respectively. Hippocampal volumes were measured on all four occasions with 3 Tesla MRI. Hippocampal volume returned to baseline during the follow-up period of 6 months. Neither the significant antidepressant effect nor the significant transient decrease in executive and verbal episodic memory tests after ECT could be related to changes in hippocampal volume. No persistent cognitive side effects were observed 1 year after ECT. The immediate increase in hippocampal volume after ECT is reversible and is not related to clinical or cognitive outcome. © 2013 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.

  16. The association of visual memory with hippocampal volume.

    Directory of Open Access Journals (Sweden)

    Andrea R Zammit

    Full Text Available In this study we investigated the role of hippocampal volume (HV in visual memory.Participants were a subsample of older adults (> = 70 years from the Einstein Aging Study. Visual performance was measured using the Complex Figure (CF copy and delayed recall tasks from the Repeatable Battery for the Assessment of Neuropsychological Status. Linear regressions were fitted to study associations between HV and visual tasks.Participants' (n = 113, mean age = 78.9 years average scores on the CF copy and delayed recall were 17.4 and 11.6, respectively. CF delayed recall was associated with total (β = .031, p = 0.001 and left (β = 0.031, p = 0.001 and right HVs (β = 0.24, p = 0.012. CF delayed recall remained significantly associated with left HV even after we also included right HV (β = 0.27, p = 0.025 and the CF copy task (β = 0.30, p = 0.009 in the model. CF copy did not show any significant associations with HV.Our results suggest that left HV contributes in retrieval of visual memory in older adults.

  17. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte; Rasmussen, Hans

    2010-01-01

    enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia. METHODS: We obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched...... healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use...... that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psychopathology. The hippocampal volume reductions appeared...

  18. Hippocampal volume changes in healthy subjects at risk of unipolar depression

    DEFF Research Database (Denmark)

    Baaré, William F C; Vinberg, Maj; Knudsen, Gitte M

    2010-01-01

    of major psychiatric disorder. High-risk twins had smaller hippocampal volumes than low-risk twins (pglobal brain tissue volumes or regional tissue volumes assessed in exploratory voxel-wise whole cerebrum analyses. In conclusion......, hippocampal volume reduction may index a predisposition to develop depression and thus may be predictive of future onset of the disorder. Further studies are needed to elucidate the role of (shared) environmental and genetic factors.......Unipolar depression is moderately heritable. It is unclear whether structural brain changes associated with unipolar depression are present in healthy persons at risk of the disorder. Here we investigated whether a genetic predisposition to unipolar depression is associated with structural brain...

  19. Reduced right posterior hippocampal volume in women with recurrent familial pure depressive disorder.

    Science.gov (United States)

    Nifosì, Francesco; Toffanin, Tommaso; Follador, Halima; Zonta, Filippo; Padovan, Giordano; Pigato, Giorgio; Carollo, Carla; Ermani, Mario; Amistà, Pietro; Perini, Giulia Ida

    2010-10-30

    Volumetric changes in mood-relevant distributed limbic/paralimbic structures have been reported in the recent literature on the course of mood disorders. Patients with unipolar and bipolar disorders have been found to have smaller hippocampal and anterior cingulate volumes. We examined hippocampal, amygdalar and anterior cingulate cortex (ACC) volumes in female patients with recurrent familial pure depressive disorder (rFPDD). We used semi-automated software for magnetic resonance imaging (MRI) to measure the volumes of the hippocampus, amygdala, ACC and subgenual prefrontal cortex (SGPFC) in 15 female patients with familial recurrent major depression (MD) and 15 healthy female subjects. Analysis of covariance, with whole brain volume as covariate, was used to compare volumetric measurements in the two groups. Volumes of the right hippocampal body and tail were significantly smaller in female patients with familial depressive disorder than in healthy subjects. Our data provide evidence of structural lateralized hippocampal body and tail abnormalities in women with familial history and recurrent episodes of depression. Although global reduction of hippocampal volume has been widely reported, data on lateralized regional reductions in familial recurrent depression had not been previously reported. Reduced volume of the right posterior hippocampus could be a structural endophenotype for recurrent depressive disorders in women. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Learning and memory alterations are associated with hippocampal N-acetylaspartate in a rat model of depression as measured by 1H-MRS.

    Directory of Open Access Journals (Sweden)

    Guangjun Xi

    Full Text Available It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS, to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI and magnetic resonance spectroscopy (MRS. Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume.

  1. Evidence for altered hippocampal function in a mouse model of the human 22q11.2 microdeletion.

    Science.gov (United States)

    Drew, Liam J; Stark, Kimberly L; Fénelon, Karine; Karayiorgou, Maria; Macdermott, Amy B; Gogos, Joseph A

    2011-08-01

    22q11.2 chromosomal deletions are recurrent copy number mutations that increase the risk of schizophrenia around thirty-fold. Deletion of the orthologous chromosomal region in mice offers an opportunity to characterize changes to neuronal structure and function that may account for the development of this disease. The hippocampus has been implicated in schizophrenia pathogenesis, is reduced in volume in 22q11.2 deletion carriers and displays altered neuronal structure in a mouse model of the mutation (Df(16)A(+/-) mice). Here we investigate hippocampal CA1 physiology, hippocampal-dependent spatial memory and novelty-induced hippocampal activation in Df(16)A(+/-) mice. We found normal spatial reference memory (as assayed by the Morris water maze test) as well as modest but potentially important deficits in physiology. In particular, a reduction in the level of inhibition of CA1 pyramidal neurons was observed, implying a decrease in interneuron activity. Additionally, deficits in LTP were observed using certain induction protocols. Induction of c-Fos expression by exploration of a novel environment suggested a relative sparing of CA1 and dentate gyrus function but showed a robust decrease in the number of activated CA3 pyramidal neurons in Df(16)A(+/-) mice. Overall, experiments performed in this 22q11.2 deletion model demonstrated deficits of various degrees across different regions of the hippocampus, which together may contribute to the increased risk of developing schizophrenia. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Smaller hippocampal volume as a vulnerability factor for the persistence of post-traumatic stress disorder.

    Science.gov (United States)

    van Rooij, S J H; Kennis, M; Sjouwerman, R; van den Heuvel, M P; Kahn, R S; Geuze, E

    2015-10-01

    Smaller hippocampal volume has often been observed in patients with post-traumatic stress disorder (PTSD). However, there is no consensus whether this is a result of stress/trauma exposure, or constitutes a vulnerability factor for the development of PTSD. Second, it is unclear whether hippocampal volume normalizes with successful treatment of PTSD, or whether a smaller hippocampus is a risk factor for the persistence of PTSD. Magnetic resonance imaging (MRI) scans and clinical interviews were collected from 47 war veterans with PTSD, 25 healthy war veterans (combat controls) and 25 healthy non-military controls. All veterans were scanned a second time with a 6- to 8-month interval, during which PTSD patients received trauma-focused therapy. Based on post-treatment PTSD symptoms, patients were divided into a PTSD group who was in remission (n = 22) and a group in whom PTSD symptoms persisted (n = 22). MRI data were analysed with Freesurfer. Smaller left hippocampal volume was observed in PTSD patients compared with both control groups. Hippocampal volume of the combat controls did not differ from healthy controls. Second, pre- and post-treatment analyses of the PTSD patients and combat controls revealed reduced (left) hippocampal volume only in the persistent patients at both time points. Importantly, hippocampal volume did not change with treatment. Our findings suggest that a smaller (left) hippocampus is not the result of stress/trauma exposure. Furthermore, hippocampal volume does not increase with successful treatment. Instead, we demonstrate for the first time that a smaller (left) hippocampus constitutes a risk factor for the persistence of PTSD.

  3. Maternal vitamin C deficiency does not reduce hippocampal volume and beta-tubulin III intensity in prenatal Guinea pigs

    DEFF Research Database (Denmark)

    Hansen, Stine Normann; Schjoldager, Janne Gram; Paidi, Maya Devi

    2016-01-01

    Marginal vitamin C (vitC) deficiency affects 5% to 10% of adults including subpopulations such as pregnant women and newborns. Animal studies link vitC deficiency to deleterious effects on the developing brain, but exactly how the brain adapts to vitC deficiency and the mechanisms behind...... the observed deficits remain largely unknown. We hypothesized that vitC deficiency in utero may lead to a decreased neuronal maturation and increased cellular death giving rise to alterations of the hippocampal morphology in a guinea pig model. Brains from prenatal guinea pig pups (n = 9-10 in each group......) subjected to either a sufficient (918 mg vitC/kg feed) or deficient (100 mg vitC/kg feed) maternal dietary regimen were assessed with regards to hippocampal volume and beta-tubulin isotype III staining intensity at 2 gestational time points (45 and 56). We found a distinct differential regional growth...

  4. A prospective evaluation of hippocampal radiation dose volume effects and memory deficits following cranial irradiation.

    Science.gov (United States)

    Ma, Ting Martin; Grimm, Jimm; McIntyre, Riley; Anderson-Keightly, Heather; Kleinberg, Lawrence R; Hales, Russell K; Moore, Joseph; Vannorsdall, Tracy; Redmond, Kristin J

    2017-11-01

    To prospectively evaluate hippocampal radiation dose volume effects and memory decline following cranial irradiation. Effects of hippocampal radiation over a wide range of doses were investigated by combining data from three prospective studies. In one, adults with small cell lung cancer received hippocampal-avoidance prophylactic cranial irradiation. In the other two, adults with glioblastoma multiforme received neural progenitor cell sparing radiation or no sparing with extra dose delivered to subventricular zone. Memory was measured by the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 6 months after radiation. Dose-volume histograms were generated and dose-response data were fitted to a nonlinear model. Of 60 patients enrolled, 30 were analyzable based on HVLT-R DR testing completion status, baseline HVLT-R DR and intracranial metastasis/recurrence or prior hippocampal resection status. We observed a dose-response of radiation to the hippocampus with regard to decline in HVLT-R DR. D50% of the bilateral hippocampi of 22.1 Gy is associated with 20% risk of decline. This prospective study demonstrates an association between hippocampal dose volume effects and memory decline measured by HVLT-R DR over a wide dose range. These data support a potential benefit of hippocampal sparing and encourage continued trial enrollment. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Survival of adult generated hippocampal neurons is altered in circadian arrhythmic mice.

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    Brooke D Rakai

    Full Text Available The subgranular zone of the hippocampal formation gives rise to new neurons that populate the dentate gyrus throughout life. Cells in the hippocampus exhibit rhythmic clock gene expression and the circadian clock is known to regulate the cycle of cell division in other areas of the body. These facts suggest that the circadian clock may regulate adult neurogenesis in the hippocampus as well. In the present study, neurogenesis in the hippocampal subgranular zone was examined in arrhythmic Bmal1 knockout (-KO mice and their rhythmic heterozygous and wildtype littermates. Proliferation and survival of newly generated subgranular zone cells were examined using bromodeoxyuridine labelling, while pyknosis (a measure of cell death and hippocampal volume were examined in cresyl violet stained sections. There was no significant difference in cellular proliferation between any of the groups, yet survival of proliferating cells, 6 weeks after the bromodeoxyuridine injection, was significantly greater in the BMAL1-KO animals. The number of pyknotic cells was significantly decreased in Bmal1-KO animals, yet hippocampal volume remained the same across genotypes. These findings suggest that while a functional circadian clock is not necessary for normal proliferation of neuronal precursor cells, the normal pruning of newly generated neurons in the hippocampus may require a functional circadian clock.

  6. Depression may be associated with hippocampal volume changes ...

    African Journals Online (AJOL)

    Adele

    pression whereas there was no relationship between cumulative time treated with antidepressants during depression.31. The HPA Axis in Depression. The HPA axis and its vulnerability to stress may be the common fac- tor in the hippocampal atrophy and associated memory deficits seen in depression and other disorders ...

  7. Reduced interference in working memory following mindfulness training is associated with increases in hippocampal volume.

    Science.gov (United States)

    Greenberg, Jonathan; Romero, Victoria L; Elkin-Frankston, Seth; Bezdek, Matthew A; Schumacher, Eric H; Lazar, Sara W

    2018-03-17

    Proactive interference occurs when previously relevant information interferes with retaining newer material. Overcoming proactive interference has been linked to the hippocampus and deemed critical for cognitive functioning. However, little is known about whether and how this ability can be improved or about the neural correlates of such improvement. Mindfulness training emphasizes focusing on the present moment and minimizing distraction from competing thoughts and memories. It improves working memory and increases hippocampal density. The current study examined whether mindfulness training reduces proactive interference in working memory and whether such improvements are associated with changes in hippocampal volume. 79 participants were randomized to a 4-week web-based mindfulness training program or a similarly structured creative writing active control program. The mindfulness group exhibited lower proactive interference error rates compared to the active control group following training. No group differences were found in hippocampal volume, yet proactive interference improvements following mindfulness training were significantly associated with volume increases in the left hippocampus. These results provide the first evidence to suggest that (1) mindfulness training can protect against proactive interference, and (2) that these benefits are related to hippocampal volumetric increases. Clinical implications regarding the application of mindfulness training in conditions characterized by impairments to working memory and reduced hippocampal volume such as aging, depression, PTSD, and childhood adversity are discussed.

  8. Hippocampal volume differences in Gulf War veterans with current versus lifetime posttraumatic stress disorder symptoms.

    Science.gov (United States)

    Apfel, Brigitte A; Ross, Jessica; Hlavin, Jennifer; Meyerhoff, Dieter J; Metzler, Thomas J; Marmar, Charles R; Weiner, Michael W; Schuff, Norbert; Neylan, Thomas C

    2011-03-15

    Decreased hippocampal volume is described in posttraumatic stress disorder (PTSD) and depression. However, it is not known whether it is a risk factor for the development of PTSD or a consequence of PTSD. We sought to determine the effects of PTSD and depressive symptoms on hippocampal volume. Clinical and magnetic resonance imaging data were collected in a cross sectional study of 244 Gulf War veterans. Measures included lifetime and current Clinician Administered PTSD Scale, Hamilton Depression Scale, Life Stressor Checklist, and Lifetime Drinking History. Magnetic resonance imaging data were acquired with a 1.5-T scanner and analyzed with automated and semiautomated image processing techniques. Eighty-two veterans had lifetime PTSD, 44 had current PTSD, and 38 had current depression. In the linear regression analysis, current PTSD symptoms (standardized coefficient β = -.25, p = .03) but neither lifetime PTSD symptoms nor current depression were associated with smaller hippocampal volume. Gender, age, history of early life trauma, education, lifetime and current alcohol use, current marijuana use, and treatment with antidepressants did not have independent effects. Participants with chronic PTSD had, on average, a smaller hippocampus compared with those with remitted PTSD. The finding that current but not lifetime PTSD symptom severity explains hippocampal size raises two possibilities: either a small hippocampus is a risk factor for lack of recovery from PTSD (trait) or PTSD effects on hippocampal volume are reversible once PTSD symptoms remit and the patient recovers (state). Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Hippocampal volume and CDR-SB can predict conversion to dementia in MCI patients

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    João Guilherme Fiorani Borgio

    2012-11-01

    Full Text Available OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB and hippocampal volume (HV as predictors of conversion from mild cognitive impairment (MCI to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.

  10. Altered neuronal excitability underlies impaired hippocampal function in an animal model of psychosis

    Directory of Open Access Journals (Sweden)

    Thomas eGrüter

    2015-05-01

    Full Text Available Psychosis is accompanied by severe attentional deficits, and impairments in associational-memory processing and sensory information processing that are ascribed to dysfunctions in prefrontal and hippocampal function. Disruptions of glutamatergic signalling may underlie these alterations: Antagonism of the N-methyl-D-aspartate receptor (NMDAR results in similar molecular, cellular, cognitive and behavioural changes in rodents and/or humans as those that occur in psychosis, raising the question as to whether changes in glutamatergic transmission may be intrinsic to the pathophysiology of the disease. In an animal model of psychosis that comprises treatment with the irreversible NMDAR-antagonist, MK801, we explored the cellular mechanisms that may underlie hippocampal dysfunction in psychosis. MK801-treatment resulted in a profound loss of hippocampal LTP that was evident 4 weeks after treatment. Whereas neuronal expression of the immediate early gene, Arc, was enhanced in the hippocampus by spatial learning in controls, MK801-treated animals failed to show activity-dependent increases in Arc expression. By contrast, a significant increase in basal Arc expression in the absence of learning was evident compared to controls. Paired-pulse facilitation was increased at the 40 ms interval indicating that NMDAR and/or fast GABAergic-mediated neurotransmission was disrupted. In line with this, MK801-treatment resulted in a significant decrease in GABA(A, and increase in GABA(B-receptor-expression in PFC, along with a significant increase of GABA(B- and NMDAR-GluN2B expression in the dentate gyrus. NMDAR-GluN1 or GluN2A subunit expression was unchanged. These data suggest that in psychosis, deficits in hippocampus-dependent memory may be caused by a loss of hippocampal LTP that arises through enhanced hippocampal neuronal excitability, altered GluN2B and GABA receptor expression and an uncoupling of the hippocampus-prefrontal cortex circuitry.

  11. Structural learning difficulties implicate altered hippocampal functioning in adults with autism spectrum disorder.

    Science.gov (United States)

    Ring, Melanie; Derwent, Claire L T; Gaigg, Sebastian B; Bowler, Dermot M

    2017-08-01

    Structural learning is fundamental to the formation of cognitive maps that are necessary for learning, memory, and spatial navigation. It also enables successful navigation of the social world, which is something that individuals with autism spectrum disorder (ASD) find particularly difficult. To master these situations, a person needs to bind pieces of information to one another and to consider the context in which experiences happen. Such binding is a capacity of the hippocampus. Although altered hippocampal function has for long been suspected to play a role in the etiology of ASD, the relevant evidence has remained inconclusive because few behavioral tests that are known to specifically necessitate preserved hippocampal function have been employed in studies of ASD. To address this gap in the literature, a total sample of 57 pairs of age and ability matched ASD and comparison participants was divided into 3 subsamples who were asked either to complete structural learning, or 1 of 2 configural learning control tasks (biconditional discrimination and transverse patterning) drawn from animal research. As predicted, ASD adults demonstrated specific difficulty with structural learning but not with other forms of configural learning. These differences were not attributable to decreased attentional shifting or increased perseveration, which would have indicated atypical frontal modulation of hippocampal processes. Instead, the observations implicate atypical hippocampal functioning as the source of structural learning difficulties in ASD. The data suggest that disturbances in domain-general cognitive processes such as structural learning, caused by altered hippocampal function, play a critical role in the etiology of ASD. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

    DEFF Research Database (Denmark)

    Holler, Jon G; Brandt, Christian T; Leib, Stephen L

    2014-01-01

    of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus. METHODS: Experimental meningitis in rats was induced by intracisternal injection of live......-pneumococcal antibodies (n = 14). T2 and diffusion weighted MR images were used to analyze changes in hippocampus volume and water diffusion (ADC). The results were correlated to ADC of the cortex, to ventricular volume, and to the extent of hippocampal apoptosis. RESULTS: Both ADC and the volume of hippocampus were...... and the volume and size of brain ventricles were positively correlated (Spearman Rank, p  0.05). CONCLUSIONS: In experimental meningitis increase in volume and water diffusion of the hippocampus are significantly...

  13. Not only cardiovascular, but also coordinative exercise increases hippocampal volume in older adults

    Directory of Open Access Journals (Sweden)

    Claudia eNiemann

    2014-08-01

    Full Text Available Cardiovascular activity has been shown to be positively associated with grey and white matter volume of, amongst others, frontal and temporal brain regions in older adults. This is particularly true for the hippocampus, a brain structure that plays an important role in learning and memory, and whose decline has been related to the development of Alzheimer´s disease. In the current study, we were interested in whether not only cardiovascular activity but also other types of physical activity, i.e., coordination training, were also positively associated with the volume of the hippocampus in older adults. For this purpose we first collected cross-sectional data on metabolic fitness (cardiovascular fitness and muscular strength and motor fitness (e.g, balance, movement speed, fine coordination. Second, we performed a 12-month randomized controlled trial. Results revealed that motor fitness but not metabolic fitness was associated with hippocampal volume. After the 12-month intervention period, both, cardiovascular and coordination training led to increases in hippocampal volume. Our findings suggest that a high motor fitness level as well as different types of physical activity were beneficial to diminish age-related hippocampal volume shrinkage or even increase hippocampal volume.

  14. MRI-Based Measurement of Hippocampal Volume in Patients With Combat-Related Posttraumatic Stress Disorder

    Science.gov (United States)

    Bremner, J. Douglas; Randall, Penny; Scott, Tammy M.; Bronen, Richard A.; Seibyl, John P.; Southwick, Steven M.; Delaney, Richard C.; McCarthy, Gregory; Charney, Dennis S.; Innis, Robert B.

    2011-01-01

    Objective Studies in nonhuman primates suggest that high levels of cortisol associated with stress have neurotoxic effects on the hippocampus, a brain structure involved in memory. The authors previously showed that patients with combat-related posttraumatic stress disorder (PTSD) had deficits in short-term memory. The purpose of this study was to compare the hippocampal volume of patients with PTSD to that of subjects without psychiatric disorder. Method Magnetic resonance imaging was used to measure the volume of the hippocampus in 26 Vietnam combat veterans with PTSD and 22 comparison subjects selected to be similar to the patients in age, sex, race, years of education, socioeconomic status, body size, and years of alcohol abuse. Results The PTSD patients had a statistically significant 8% smaller right hippocampal volume relative to that of the comparison subjects, but there was no difference in the volume of other brain regions (caudate and temporal lobe). Deficits in short-term verbal memory as measured with the Wechsler Memory Scale were associated with smaller right hippocampal volume in the PTSD patients only. Conclusions These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory. PMID:7793467

  15. Memory function and hippocampal volumes in preterm born very-low-birth-weight (VLBW) young adults.

    Science.gov (United States)

    Aanes, Synne; Bjuland, Knut Jørgen; Skranes, Jon; Løhaugen, Gro C C

    2015-01-15

    The hippocampi are regarded as core structures for learning and memory functions, which is important for daily functioning and educational achievements. Previous studies have linked reduction in hippocampal volume to working memory problems in very low birth weight (VLBW; ≤ 1500 g) children and reduced general cognitive ability in VLBW adolescents. However, the relationship between memory function and hippocampal volume has not been described in VLBW subjects reaching adulthood. The aim of the study was to investigate memory function and hippocampal volume in VLBW young adults, both in relation to perinatal risk factors and compared to term born controls, and to look for structure-function relationships. Using Wechsler Memory Scale-III and MRI, we included 42 non-disabled VLBW and 61 control individuals at age 19-20 years, and related our findings to perinatal risk factors in the VLBW-group. The VLBW young adults achieved lower scores on several subtests of the Wechsler Memory Scale-III, resulting in lower results in the immediate memory indices (visual and auditory), the working memory index, and in the visual delayed and general memory delayed indices, but not in the auditory delayed and auditory recognition delayed indices. The VLBW group had smaller absolute and relative hippocampal volumes than the controls. In the VLBW group inferior memory function, especially for the working memory index, was related to smaller hippocampal volume, and both correlated with lower birth weight and more days in the neonatal intensive care unit (NICU). Our results may indicate a structural-functional relationship in the VLBW group due to aberrant hippocampal development and functioning after preterm birth. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Early childhood trauma and hippocampal volumes in patients with epileptic and psychogenic seizures.

    Science.gov (United States)

    Johnstone, Benjamin; Velakoulis, Dennis; Yuan, Cheng Yi; Ang, Anthony; Steward, Chris; Desmond, Patricia; O'Brien, Terence J

    2016-11-01

    Exposure to early life childhood trauma has been implicated as resulting in a vulnerability to epileptic and psychogenic nonepileptic seizures (PNES), hippocampal atrophy, and psychiatric disorders. This study aimed to explore the relationships between childhood trauma, epilepsy, PNES, and hippocampal volume in patients admitted to a video-electroencephalogram monitoring (VEM) unit. One hundred thirty-one patients were recruited from the Royal Melbourne Hospital VEM unit. The diagnostic breakdown of this group was: temporal lobe epilepsy (TLE) (32), other epilepsy syndromes (35), PNES (47), other nonepileptic syndromes (5), both epilepsy and PNES (6), and uncertain diagnosis (6). All patients completed a questionnaire assessing exposure to childhood trauma, the Childhood Trauma Questionnaire (CTQ), as well as questionnaires assessing psychiatric symptomatology (SCL-90-R), Anxiety and Depression (HADS), quality of life (QOLIE-98) and cognition (NUCOG). Volumetric coronal T1 MRI scans were available for 84 patients. Hippocampal volumes were manually traced by a blinded operator. The prevalence of childhood trauma in patients with PNES was higher than in patients with other diagnoses (p=0.005), and the group with PNES overall scored significantly higher on the CTQ (p=0.002). No association was found between CTQ scores and hippocampal volumes; however, patients with a history of sexual abuse were found to have smaller left hippocampal volumes than patients who had not (p=0.043). Patients reporting having experienced childhood trauma scored lower on measures of quality of life and higher on measures of psychiatric symptomatology. Patients with PNES report having experienced significantly more childhood trauma than those with epileptic seizures, and in both groups there was a relationship between a history of having experienced sexual abuse and reduced left hippocampal volume. Patients with PNES and those with epilepsy who have a history of childhood trauma have overall

  17. Childhood trauma and hippocampal and amygdalar volumes in first-episode psychosis.

    Science.gov (United States)

    Hoy, Katrina; Barrett, Suzanne; Shannon, Ciaran; Campbell, Clodagh; Watson, David; Rushe, Teresa; Shevlin, Mark; Bai, Feng; Cooper, Stephen; Mulholland, Ciaran

    2012-11-01

    A history of childhood trauma is common in individuals who later develop psychosis. Similar neuroanatomical abnormalities are observed in people who have been exposed to childhood trauma and people with psychosis. However, the relationship between childhood trauma and such abnormalities in psychosis has not been investigated. This study aimed to explore the association between the experience of childhood trauma and hippocampal and amygdalar volumes in a first-episode psychosis (FEP) population. The study employed an observational retrospective design. Twenty-one individuals, who had previously undergone magnetic resonance imaging procedures as part of the longitudinal Northern Ireland First-Episode Psychosis Study, completed measures assessing traumatic experiences and were included in the analysis. Data were subject to correlation analyses (r and r (pb)). Potential confounding variables (age at FEP and delay to scan from recruitment) were selected a priori for inclusion in multiple regression analyses. There was a high prevalence of lifetime (95%) and childhood (76%) trauma in the sample. The experience of childhood trauma was a significant predictor of left hippocampal volume, although age at FEP also significantly contributed to this model. There was no significant association between predictor variables and right hippocampal volume. The experience of childhood trauma was a significant predictor of right and total amygdalar volumes and the hippocampal/amygdalar complex volume as a whole. The findings indicate that childhood trauma is associated with neuroanatomical measures in FEP. Future research controlling for childhood traumatic experiences may contribute to explaining brain morphology in people with psychosis.

  18. Hippocampal volume in older adults at risk of cognitive decline: the role of sleep, vascular risk, and depression.

    Science.gov (United States)

    Elcombe, Emma L; Lagopoulos, Jim; Duffy, Shantel L; Lewis, Simon J G; Norrie, Louisa; Hickie, Ian B; Naismith, Sharon L

    2015-01-01

    Decreased hippocampal volume in older adults is associated with neurodegenerative and psychiatric diseases. Several modifiable risk factors have been associated with the size of this structure, however the relative contribution of these factors to hippocampal atrophy is unclear. This study aimed to examine the relationship between modifiable risk factors and hippocampal volume in older adults at risk of cognitive decline. Two hundred and eighteen participants (mean age = 67.3 years, MMSE = 28.6) with mood and/or memory complaints underwent clinical and neuropsychological assessment, and magnetic resonance imaging. Measures of depression, global cognitive functioning, exercise, vascular health, cognitive reserve, sleep, and memory were collected. Hippocampal volumes were derived using image segmentation as implemented by FMRIB Software Library. Smaller hippocampal volumes were strongly associated with poorer verbal learning and memory as well as diagnoses of either multiple or amnestic mild cognitive impairment. Based on univariate correlations, multivariable regressions were performed (controlling for age and total intracranial volume) to determine which modifiable risk factors were associated with hippocampal volume. For the left hippocampus, poor sleep efficiency and greater than five years untreated depressive illness remained significant predictors. For the right hippocampus, diabetes and low diastolic blood pressure significant predictors. Although their contribution is small, lower sleep efficiency, low blood pressure, diabetes, and untreated depression are associated with reduced hippocampal volumes. Studies exploring the impact of early intervention for these risk factors on hippocampal integrity are warranted.

  19. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    Science.gov (United States)

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Proteome Alterations of Hippocampal Cells Caused by Clostridium botulinum C3 Exoenzyme.

    Science.gov (United States)

    Schröder, Anke; Rohrbeck, Astrid; Just, Ingo; Pich, Andreas

    2015-11-06

    C3bot from Clostridium botulinum is a bacterial mono-ADP-ribosylating enzyme, which transfers an ADP-ribose moiety onto the small GTPases Rho A/B/C. C3bot and the catalytic inactive mutant (C3E174Q) cause axonal and dendritic growth as well as branching in primary hippocampal neurons. In cultured murine hippocampal HT22 cells, protein abundances were analyzed in response to C3bot or C3E174Q treatment using a shotgun proteomics approach. Proteome analyses were performed at four time points over 6 days. More than 4000 protein groups were identified at each time point and quantified in triplicate analyses. On day one, 46 proteins showed an altered abundance, and after 6 days, more than 700 proteins responded to C3bot with an up- or down-regulation. In contrast, C3E174Q had no provable impact on protein abundance. Protein quantification was verified for several proteins by multiple reaction monitoring. Data analysis of altered proteins revealed different cellular processes that were affected by C3bot. They are particularly involved in mitochondrial and lysosomal processes, adhesion, carbohydrate and glucose metabolism, signal transduction, and nuclear proteins of translation and ribosome biogenesis. The results of this study gain novel insights into the function of C3bot in hippocampal cells.

  1. Hippocampal neurogenesis and volume in migrating and wintering semipalmated sandpipers (Calidris pusilla).

    Science.gov (United States)

    de Morais Magalhães, Nara Gyzely; Guerreiro Diniz, Cristovam; Guerreiro Diniz, Daniel; Pereira Henrique, Ediely; Corrêa Pereira, Patrick Douglas; Matos Moraes, Isis Ananda; Damasceno de Melo, Mauro André; Sherry, David Francis; Wanderley Picanço Diniz, Cristovam

    2017-01-01

    Long distance migratory birds find their way by sensing and integrating information from a large number of cues in their environment. These cues are essential to navigate over thousands of kilometers and reach the same breeding, stopover, and wintering sites every year. The semipalmated sandpiper (Calidris pusilla) is a long-distance migrant that breeds in the arctic tundra of Canada and Alaska and winters on the northeast coast of South America. Its fall migration includes a 5,300-kilometer nonstop flight over the Atlantic Ocean. The avian hippocampus has been proposed to play a central role in the integration of multisensory spatial information for navigation. Hippocampal neurogenesis may contribute to hippocampal function and a variety of factors including cognitive activity, exercise, enrichment, diet and stress influence neurogenesis in the hippocampus. We quantified hippocampal neurogenesis and volume in adult migrating and wintering semipalmated sandpipers using stereological counts of doublecortin (DCX) immunolabeled immature neurons. We found that birds captured in the coastal region of Bragança, Brazil during the wintering period had more DCX positive neurons and larger volume in the hippocampus than individuals captured in the Bay of Fundy, Canada during fall migration. We also estimate the number of NeuN immunolabeled cells in migrating and wintering birds and found no significant differences between them. These findings suggest that, at this time window, neurogenesis just replaced neurons that might be lost during the transatlantic flight. Our findings also show that in active fall migrating birds, a lower level of adult hippocampal neurogenesis is associated with a smaller hippocampal formation. High levels of adult hippocampal neurogenesis and a larger hippocampal formation found in wintering birds may be late occurring effects of long distance migratory flight or the result of conditions the birds experienced while wintering.

  2. Hippocampal neurogenesis and volume in migrating and wintering semipalmated sandpipers (Calidris pusilla.

    Directory of Open Access Journals (Sweden)

    Nara Gyzely de Morais Magalhães

    Full Text Available Long distance migratory birds find their way by sensing and integrating information from a large number of cues in their environment. These cues are essential to navigate over thousands of kilometers and reach the same breeding, stopover, and wintering sites every year. The semipalmated sandpiper (Calidris pusilla is a long-distance migrant that breeds in the arctic tundra of Canada and Alaska and winters on the northeast coast of South America. Its fall migration includes a 5,300-kilometer nonstop flight over the Atlantic Ocean. The avian hippocampus has been proposed to play a central role in the integration of multisensory spatial information for navigation. Hippocampal neurogenesis may contribute to hippocampal function and a variety of factors including cognitive activity, exercise, enrichment, diet and stress influence neurogenesis in the hippocampus. We quantified hippocampal neurogenesis and volume in adult migrating and wintering semipalmated sandpipers using stereological counts of doublecortin (DCX immunolabeled immature neurons. We found that birds captured in the coastal region of Bragança, Brazil during the wintering period had more DCX positive neurons and larger volume in the hippocampus than individuals captured in the Bay of Fundy, Canada during fall migration. We also estimate the number of NeuN immunolabeled cells in migrating and wintering birds and found no significant differences between them. These findings suggest that, at this time window, neurogenesis just replaced neurons that might be lost during the transatlantic flight. Our findings also show that in active fall migrating birds, a lower level of adult hippocampal neurogenesis is associated with a smaller hippocampal formation. High levels of adult hippocampal neurogenesis and a larger hippocampal formation found in wintering birds may be late occurring effects of long distance migratory flight or the result of conditions the birds experienced while wintering.

  3. Common variants at 12q14 and 12q24 are associated with hippocampal volume

    NARCIS (Netherlands)

    Bis, Joshua C.; Decarli, Charles; Smith, Albert Vernon; van der Lijn, Fedde; Crivello, Fabrice; Fornage, Myriam; Debette, Stephanie; Shulman, Joshua M.; Schmidt, Helena; Srikanth, Velandai; Schuur, Maaike; Yu, Lei; Choi, Seung-Hoan; Sigurdsson, Sigurdur; Verhaaren, Benjamin F. J.; DeStefano, Anita L.; Lambert, Jean-Charles; Jack, Clifford R.; Struchalin, Maksim; Stankovich, Jim; Ibrahim-Verbaas, Carla A.; Fleischman, Debra; Zijdenbos, Alex; den Heijer, Tom; Mazoyer, Bernard; Coker, Laura H.; Enzinger, Christian; Danoy, Patrick; Amin, Najaf; Arfanakis, Konstantinos; van Buchem, Mark A.; de Bruijn, Renée F. A. G.; Beiser, Alexa; Dufouil, Carole; Huang, Juebin; Cavalieri, Margherita; Thomson, Russell; Niessen, Wiro J.; Chibnik, Lori B.; Gislason, Gauti K.; Hofman, Albert; Pikula, Aleksandra; Amouyel, Philippe; Freeman, Kevin B.; Phan, Thanh G.; Oostra, Ben A.; Stein, Jason L.; Medland, Sarah E.; Vasquez, Alejandro Arias; Hibar, Derrek P.; Wright, Margaret J.; Franke, Barbara; Martin, Nicholas G.; Thompson, Paul M.; Nalls, Michael A.; Uitterlinden, Andre G.; Au, Rhoda; Elbaz, Alexis; Beare, Richard J.; van Swieten, John C.; Lopez, Oscar L.; Harris, Tamara B.; Chouraki, Vincent; Breteler, Monique M. B.; de Jager, Philip L.; Becker, James T.; Vernooij, Meike W.; Knopman, David; Fazekas, Franz; Wolf, Philip A.; van der Lugt, Aad; Gudnason, Vilmundur; Longstreth, W. T.; Brown, Matthew A.; Bennett, David A.; van Duijn, Cornelia M.; Mosley, Thomas H.; Schmidt, Reinhold; Tzourio, Christophe; Launer, Lenore J.; Ikram, M. Arfan; Seshadri, Sudha; Arias Vasquez, Alejandro; Senstad, Rudy E.; Winkler, Anderson M.; Toro, Roberto; Appel, Katja; Bartecek, Richard; Bergmann, Ørjan; Bernard, Manon; Brown, Andrew A.; Cannon, Dara M.; Chakravarty, Mallar; Christoforou, Andrea; Domin, Martin; Grimm, Oliver; Hollinshead, Marisa; Holmes, Avram J.; Homuth, Georg; Hottenga, Jouke-Jan; Langan, Camilla; Lopez, Lorna M.; Hansell, Narelle K.; Hwang, Kristy S.; Kim, Sungeun; Laje, Gonzalo; Lee, Phil H.; Liu, Xinmin; Loth, Eva; Lourdusamy, Anbarasu; Maniega, Susana Muñoz; Mattingsdal, Morten; Mohnke, Sebastian; Nho, Kwangsik; Nugent, Allison C.; O'Brien, Carol; Papmeyer, Martina; Pütz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rijpkema, Mark; Risacher, Shannon L.; Roddey, J. Cooper; Rose, Emma J.; Ryten, Mina; Shen, Li; Sprooten, Emma; Strengman, Eric; Teumer, Alexander; Trabzuni, Daniah; Turner, Jessica; van Eijk, Kristel; van Erp, Theo G. M.; van Tol, Marie-Jose; Wittfeld, Katharina; Wolf, Christiane; Woudstra, Saskia; Aleman, Andre; Alhusaini, Saud; Almasy, Laura; Binder, Elisabeth B.; Brohawn, David G.; Cantor, Rita M.; Carless, Melanie A.; Corvin, Aiden; Czisch, Michael; Curran, Joanne E.; Davies, Gail; de Almeida, Marcio A. A.; Delanty, Norman; Depondt, Chantal; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fagerness, Jesen; Fox, Peter T.; Freimer, Nelson B.; Gill, Michael; Göring, Harald H. H.; Hagler, Donald J.; Hoehn, David; Holsboer, Florian; Hoogman, Martine; Hosten, Norbert; Jahanshad, Neda; Johnson, Matthew P.; Kasperaviciute, Dalia; Kent, Jack W.; Kochunov, Peter; Lancaster, Jack L.; Lawrie, Stephen M.; Liewald, David C.; Mandl, René; Matarin, Mar; Mattheisen, Manuel; Meisenzahl, Eva; Melle, Ingrid; Moses, Eric K.; Mühleisen, Thomas W.; Nauck, Matthias; Nöthen, Markus M.; Olvera, Rene L.; Pandolfo, Massimo; Pike, G. Bruce; Puls, Ralf; Reinvang, Ivar; Rentería, Miguel E.; Rietschel, Marcella; Roffman, Joshua L.; Royle, Natalie A.; Rujescu, Dan; Savitz, Jonathan; Schnack, Hugo G.; Schnell, Knut; Seiferth, Nina; Smith, Colin; Steen, Vidar M.; Valdés Hernández, Maria C.; van den Heuvel, Martijn; van der Wee, Nic J.; van Haren, Neeltje E. M.; Veltman, Joris A.; Völzke, Henry; Walker, Robert; Westlye, Lars T.; Whelan, Christopher D.; Agartz, Ingrid; Boomsma, Dorret I.; Cavalleri, Gianpiero L.; Dale, Anders M.; Djurovic, Srdjan; Drevets, Wayne C.; Hagoort, Peter; Hall, Jeremy; Heinz, Andreas; Foroud, Tatiana M.; Le Hellard, Stephanie; Macciardi, Fabio; Montgomery, Grant W.; Poline, Jean Baptiste; Porteous, David J.; Sisodiya, Sanjay M.; Starr, John M.; Sussmann, Jessika; Toga, Arthur W.; Veltman, Dick J.; Walter, Henrik; Weiner, Michael W.; Andreassen, Ole A.; Apostolova, Liana G.; Bastin, Mark E.; Blangero, John; Brunner, Han G.; Buckner, Randy L.; Cichon, Sven; Coppola, Giovanni; de Zubicaray, Greig I.; Deary, Ian J.; Donohoe, Gary; de Geus, Eco J. C.; Espeseth, Thomas; Fernández, Guillén; Glahn, David C.; Grabe, Hans J.; Hardy, John; Hulshoff Pol, Hilleke E.; Jenkinson, Mark; Kahn, René S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Meyer-Lindenberg, Andreas; Morris, Derek W.; Müller-Myhsok, Bertram; Nichols, Thomas E.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W.; Potkin, Steven G.; Sämann, Philipp G.; Saykin, Andrew J.; Schumann, Gunter; Smoller, Jordan W.; Wardlaw, Joanna M.; Weale, Michael E.

    2012-01-01

    Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n

  4. Amygdala to hippocampal volume ratio is associated with negative memory bias in healthy subjects

    NARCIS (Netherlands)

    Gerritsen, L.; Rijpkema, M.J.P.; Oostrom, I.I.H. van; Buitelaar, J.K.; Franke, B.; Fernandez, G.S.E.; Tendolkar, I.

    2012-01-01

    Background. Negative memory bias is thought to be one of the main cognitive risk and maintenance factors for depression, but its neural substrates are largely unknown. Here, we studied whether memory bias is related to amygdala and hippocampal volume, two structures that are critical for emotional

  5. What causes the hippocampal volume decrease in depression? : Are neurogenesis, glial changes and apoptosis implicated?

    NARCIS (Netherlands)

    Czeh, B.; Lucassen, P.J.

    2007-01-01

    Even though in vivo imaging studies document significant reductions of hippocampal volume in depressed patients, the exact underlying cellular mechanisms are unclear. Since stressful life events are associated with an increased risk of developing depression, preclinical studies in which animals are

  6. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte; Rasmussen, Hans

    2010-01-01

    enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia. METHODS: We obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched...

  7. Beyond dizziness: virtual navigation, spatial anxiety and hippocampal volume in bilateral vestibulopathy

    Directory of Open Access Journals (Sweden)

    Olympia eKremmyda

    2016-03-01

    Full Text Available Bilateral vestibulopathy (BVP is defined as the impairment or loss of function of either the labyrinths or the eighth nerves. Patients with total BVP due to bilateral vestibular nerve section exhibit difficulties in spatial memory and navigation and show a loss of hippocampal volume. In clinical practice, most patients do not have a complete loss of function but rather an asymmetrical residual functioning of the vestibular system. The purpose of the current study was to investigate navigational ability and hippocampal atrophy in BVP patients with residual vestibular function. Fifteen patients with BVP and a group of age- and gender- matched healthy controls were examined. Self-reported questionnaires on spatial anxiety and wayfinding were used to assess the applied strategy of wayfinding and quality of life. Spatial memory and navigation were tested directly using a virtual Morris Water Maze Task. The hippocampal volume of these two groups was evaluated by voxel-based morphometry. In the patients, the questionnaire showed a higher spatial anxiety and the Morris Water Maze Task a delayed spatial learning performance. MRI revealed a significant decrease in the gray matter mid-hippocampal volume (Left: p = 0.006, Z = 4.58, Right: p < 0.001, Z = 3.63 and posterior parahippocampal volume (Right: p = 0.005, Z = 4.65, Left: p < 0.001, Z = 3.87 compared to those of healthy controls. In addition, a decrease in hippocampal formation volume correlated with a more dominant route-finding strategy. Our current findings demonstrate that even partial bilateral vestibular loss leads to anatomical and functional

  8. Comparison between visual assessment of MTA and hippocampal volumes in an elderly, non-demented population

    Energy Technology Data Exchange (ETDEWEB)

    Cavallin, Lena; Axelsson, Rimma [CLINTEC, Div. of Medical Imaging and Technology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Dept. of Radiology, Karolinska Univ. Hospital, Stockholm (Sweden)], e-mail: lena.cavallin@karolinska.se; Bronge, Lena [CLINTEC, Div. of Medical Imaging and Technology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Aleris Diagnostics, Stockholm (Sweden); Zhang, Yi [NVS, Novum, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Oeksengaard, Anne-Rita [NVS, Novum, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Ulleval Univ. Hospital and Asker and Baerum Hospital, Oslo (Norway); Wahlund, Lars-Olof [NVS, Novum, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Swedish Brain Power, Karolinska Univ. Hospital, Stockholm (Sweden); Fratiglioni, Laura [ARC Karolinska Inst. Stockholm (Sweden)

    2012-06-15

    Background: It is important to have a replicable easy method for monitoring atrophy progression in Alzheimer's disease. Volumetric methods for calculating hippocampal volume are time-consuming and commonly used in research. Visual assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for clinical use. This method has not been tested in a large non-demented population in comparison with volumetry measurements. Since hippocampal volume decreases with time even in normal aging there is also a need to study the normal age differences of medial temporal lobe atrophy. Purpose: To compare visual assessment of medial temporal lobe atrophy (vaMTA) with hippocampal volume in a healthy, non-demented elderly population. To describe normal ageing using vaMTA. Material and Methods: Non-demented individuals aged 60, 66, 72, 78, 81, 84, and {>=}87 years old were recruited from the Swedish National study on Ageing and Care in Kungsholmen (SNAC-K), Sweden. Standard magnetic resonance imaging (MRI) scans, vaMTA, and calculations of hippocampal volumes were performed in 544 subjects. Results: Significant correlation (rs = -0.32, P < 0.001, sin; and rs = -0.26, P < 0.001, dx) was found between hippocampal volume measurements and vaMTA. In normal ageing, almost 95% of {<=}66-year-olds had a medial temporal lobe atrophy (MTA) score {<=}1, with possible scores ranging from 0 to 4. Subjects aged 72, 78, and 81 years scored {<=}2, while the two oldest age groups had scores {<=}3. Conclusion: There was a highly significant correlation between volumetric measurements of the hippocampus and MTA scoring. In normal ageing, there is increasing MTA score. For non-demented elderly individuals {<=}70 years, an MTA score of 0-1 may be considered normal, compared with MTA {<=}2 for 70-80-years and MTA 3 for >80-year-old individuals.

  9. Long-Term Treatment with Paroxetine Increases Verbal Declarative Memory and Hippocampal Volume in Posttraumatic Stress Disorder

    Science.gov (United States)

    Vermetten, Eric; Vythilingam, Meena; Southwick, Steven M.; Charney, Dennis S.; Bremner, J. Douglas

    2011-01-01

    Background Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. Methods Declarative memory was assessed with the Wechsler Memory Scale–Revised and Selective Reminding Test before and after 9–12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. Results Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. Conclusions These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD. PMID:14512209

  10. Volume of hippocampal subfields and episodic memory in childhood and adolescence.

    Science.gov (United States)

    Lee, Joshua K; Ekstrom, Arne D; Ghetti, Simona

    2014-07-01

    Episodic memory critically depends on the hippocampus to bind the features of an experience into memory. Episodic memory develops in childhood and adolescence, and hippocampal changes during this period may contribute to this development. Little is known, however, about how the hippocampus contributes to episodic memory development. The hippocampus is comprised of several cytoarchitectural subfields with functional significance for episodic memory. However, hippocampal subfields have not been assessed in vivo during child development, nor has their relation with episodic memory been assessed during this period. In the present study, high-resolution T2-weighted images of the hippocampus were acquired in 39 children and adolescents aged 8 to 14 years (M=11.30, SD=2.38), and hippocampal subfields were segmented using a protocol previously validated in adult populations. We first validated the method in children and adolescents and examined age-related differences in hippocampal subfields and correlations between subfield volumes and episodic memory. Significant age-related increases in the subfield volume were observed into early adolescence in the right CA3/DG and CA1. The right CA3/DG subfield volumes were positively correlated with accurate episodic memory for item-color relations, and the right CA3/DG and subiculum were negatively correlated with item false alarm rates. Subfield development appears to follow a protracted developmental trajectory, and likely plays a pivotal role in episodic memory development. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Prolonged cannabinoid exposure alters GABAA receptor mediated synaptic function in cultured hippocampal neurons

    Science.gov (United States)

    Deshpande, Laxmikant S.; Blair, Robert. E.; DeLorenzo, Robert. J.

    2011-01-01

    Developing cannabinoid based medication along with marijuana’s recreational use makes it important to investigate molecular adaptations the endocannabinoid system undergoes following prolonged use and withdrawal. Repeated cannabinoid administration results in development of tolerance and produces withdrawal symptoms that may include seizures. Here we employed electrophysiological and immunochemical techniques to investigate the effects of prolonged CB1 receptor agonist exposure on cultured hippocampal neurons. Approximately 60% of CB1 receptors colocalize to GABAergic terminals in hippocampal cultures. Prolonged treatment with the cannabinamimetic WIN 55,212-2 (+WIN, 1μM, 24-h) caused profound CB1 receptor downregulation accompanied by neuronal hyperexcitability. Furthermore, prolonged +WIN treatment resulted in increased GABA release as indicated by increased mIPSC frequency, a diminished GABAergic inhibition as indicated by reduction in mIPSC amplitude and a reduction in GABAA channel number. Additionally, surface staining for the GABAA β2/3 receptor subunits was decreased, while no changes in staining for the presynaptic vesicular GABA transporter were observed, indicating that GABAergic terminals remained intact. These findings demonstrate that agonist-induced downregulation of the CB1 receptor in hippocampal cultures results in neuronal hyperexcitability that may be attributed, in part, to alterations in both presynaptic GABA release mechanisms and postsynaptic GABAA receptor function demonstrating a novel role for cannabinoid-dependent presynaptic control of neuronal transmission. PMID:21324315

  12. Distinct subcortical volume alterations in pediatric and adult OCD

    Science.gov (United States)

    Boedhoe, Premika S.W.; Schmaal, Lianne; Abe, Yoshinari; Ameis, Stephanie H.; Arnold, Paul D.; Batistuzzo, Marcelo C.; Benedetti, Francesco; Beucke, Jan C.; Bollettini, Irene; Bose, Anushree; Brem, Silvia; Calvo, Anna; Cheng, Yuqi; Cho, Kang Ik K.; Dallaspezia, Sara; Denys, Damiaan; Fitzgerald, Kate D.; Fouche, Jean-Paul; Giménez, Mònica; Gruner, Patricia; Hanna, Gregory L.; Hibar, Derrek P.; Hoexter, Marcelo Q.; Huyser, Chaim; Ikari, Keisuke; Jahanshad, Neda; Kathmann, Norbert; Kaufmann, Christian; Koch, Kathrin; Kwon, Jun Soo; Lazaro, Luisa; Liu, Yanni; Lochner, Christine; Marsh, Rachel; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Menchón, José M.; Minuzzii, Luciano; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswamy, Janardhanan C.; Piras, Fabrizio; Piras, Federica; Pittenger, Christopher; Reddy, Y.C. Janardhan; Sato, Joao R.; Simpson, H. Blair; Soreni, Noam; Soriano-Mas, Carles; Spalletta, Gianfranco; Stevens, Michael C.; Szeszko, Philip R.; Tolin, David F.; Venkatasubramanian, Ganesan; Walitza, Susanne; Wang, Zhen; van Wingen, Guido A.; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, Qing; Thompson, Paul M.; Stein, Dan J.; van den Heuvel, Odile A.

    2016-01-01

    Objective Structural brain imaging studies in Obsessive-Compulsive Disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in disease profile and developmental stage. Methods To address these limitations, we conducted a meta- and mega-analysis of data from OCD sites worldwide. T1 images from 1,830 OCD patients and 1,759 controls were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ in OCD patients and healthy controls. We additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. Results The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen’s d=−0.13; p=5.1x10−3, % difference −2.80) and larger pallidum volumes (d=0.16; p=1.6x10−3, % difference 3.16) compared to adult controls. Both effects were stronger in medicated patients compared to controls (d=−0.29; p=2.4x10−5, % difference −4.18 and d=0.29; p=1.2x10−5, % difference 4.38, respectively). Unmedicated pediatric patients had larger thalamic volumes (d=0.38, p=2.1x10−3) compared to pediatric controls. None of these findings were mediated by sample characteristics such as mean age or field strength. Overall the mega-analysis yielded similar results. Conclusion Our study indicates a different pattern of subcortical abnormalities in pediatric versus adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. This highlights the potential importance of neurodevelopmental alterations in OCD, and suggests that further research on neuroplasticity in OCD may be useful. PMID:27609241

  13. Hippocampal subregion volume changes associated with antipsychotic treatment in first-episode psychosis.

    Science.gov (United States)

    Rhindress, K; Robinson, D G; Gallego, J A; Wellington, R; Malhotra, A K; Szeszko, P R

    2017-07-01

    Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis. A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1-3, posterior CA1-3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability. Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans. This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.

  14. Adiposity is inversely associated with hippocampal volume in African Americans and European Americans with diabetes.

    Science.gov (United States)

    Hsu, Fang-Chi; Yuan, Mingxia; Bowden, Donald W; Xu, Jianzhao; Smith, S Carrie; Wagenknecht, Lynne E; Langefeld, Carl D; Divers, Jasmin; Register, Thomas C; Carr, J Jeffrey; Williamson, Jeff D; Sink, Kaycee M; Maldjian, Joseph A; Freedman, Barry I

    To assess associations between body mass index (BMI), waist circumference (WC), and computed tomography-determined volumes of pericardial, visceral, and subcutaneous adipose tissue with magnetic resonance imaging-(MRI) based cerebral structure and cognitive performance in individuals with type 2 diabetes (T2D). This study was performed in 348 African Americans (AAs) and 256 European Americans (EAs) with T2D. Associations between adiposity measures with cerebral volumes of white matter (WMV), gray matter (GMV), white matter lesions, hippocampal GMV, and hippocampal WMV, cognitive performance and depression were examined using marginal models incorporating generalized estimating equations. All models were adjusted for age, sex, education, smoking, HbA1c, hypertension, statins, cardiovascular disease, MRI scanner (MRI outcomes only), and time between scans; some neuroimaging measures were additionally adjusted for intracranial volume. Participants were 59.9% female with mean (SD) age 57.7(9.3)years, diabetes duration 9.6(6.8)years, and HbA1c 7.8(1.9)%. In AAs, inverse associations were detected between hippocampal GMV and both BMI (β [95% CI]-0.18 [-0.30, -0.07], P=0.0018) and WC (-0.23 [-0.35, -0.12], P=0.0001). In the full bi-ethnic sample, inverse associations were detected between hippocampal WMV and WC (P≤0.0001). Positive relationships were observed between BMI (P=0.0007) and WC (P<0.0001) with depression in EAs. In patients with T2D, adiposity is inversely associated with hippocampal gray and white matter volumes. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Voluntary alcohol intake after noise exposure in adolescent rats: Hippocampal-related behavioral alterations.

    Science.gov (United States)

    Miceli, M; Molina, S J; Forcada, A; Acosta, G B; Guelman, L R

    2018-01-15

    Different physical or chemical agents, such as noise or alcohol, can induce diverse behavioral and biochemical alterations. Considering the high probability of young people to undergo consecutive or simultaneous exposures, the aim of the present work was to investigate in an animal model if noise exposure at early adolescence could induce hippocampal-related behavioral changes that might be modified after alcohol intake. Male Wistar rats (28-days-old) were exposed to noise (95-97 dB, 2 h). Afterwards, animals were allowed to voluntarily drink alcohol (10% ethanol in tap water) for three consecutive days, using the two-bottle free choice paradigm. After that, hippocampal-related memory and anxiety-like behavior tests were performed. Results show that whereas noise-exposed rats presented deficits in habituation memory, those who drank alcohol exhibited impairments in associative memory and anxiety-like behaviors. In contrast, exposure to noise followed by alcohol intake showed increases in exploratory and locomotor activities as well as in anxiety-like behaviors, unlike what was observed using each agent separately. Finally, lower levels of alcohol intake were measured in these animals when compared with those that drank alcohol and were not exposed to noise. Present findings demonstrate that exposure to physical and chemical challenges during early adolescence might induce behavioral alterations that could differ depending on the schedule used, suggesting a high vulnerability of rat developing brain to these socially relevant agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Influence of parental care on offspring hippocampal volume in young adults varies as a function of overprotection

    OpenAIRE

    Wang, Yinan; Song, Yiying; Li, Xueting; Zhang, Lin; Liu, Jia

    2017-01-01

    Parental care results in increased hippocampal volumes through adaptive stress responses in developing animals. However, human studies have not yet provided consistent findings analogous to the animal literature, possibly because parental care in humans is likely intermingled with parental overprotection, as suggested by the optimal parenting theory. Here, we tested the hypothesis that the effect of parental care on offspring hippocampal volume varies as a function of parental overprotection ...

  17. Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.

    Science.gov (United States)

    Winkle, Cortney C; Olsen, Reid H J; Kim, Hyojin; Moy, Sheryl S; Song, Juan; Gupton, Stephanie L

    2016-05-04

    During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory. Copyright © 2016 the authors 0270-6474/16/364940-19$15.00/0.

  18. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze.

    Directory of Open Access Journals (Sweden)

    Jesús J. Hernández-Pérez

    2015-10-01

    Full Text Available Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS, which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn is located between the reticularis pontis oralis and the medial septum (MS, in close relation with the posterior hypothalamic nucleus (PHn, all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS. Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. In agreement with this hypothesis, serotonin depletion in the SUMn/PHn results in deficient spatial learning and alterations in CA1 theta activity-related learning in a Morris water maze. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory. We infused 5,7-DHT bilaterally into the SUMn in rats and evaluated place learning in the standard Morris water maze task. Hippocampal (CA1 and dentate gyrus, septal and SUMn EEG were recorded during training of the test. The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results

  19. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze.

    Science.gov (United States)

    Hernández-Pérez, J Jesús; Gutiérrez-Guzmán, Blanca E; López-Vázquez, Miguel Á; Olvera-Cortés, María E

    2015-01-01

    Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS. Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. In agreement with this hypothesis, serotonin depletion in the SUMn/PHn results in deficient spatial learning and alterations in CA1 theta activity-related learning in a Morris water maze. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory. We infused 5,7-DHT bilaterally into the SUMn in rats and evaluated place learning in the standard Morris water maze task. Hippocampal (CA1 and dentate gyrus), septal and SUMn EEG were recorded during training of the test. The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results provide evidence in

  20. Hippocampal volume and serotonin transporter polymorphism in major depressive disorder

    DEFF Research Database (Denmark)

    Ahdidan, Jamila; Foldager, Leslie; Rosenberg, Raben

    2013-01-01

    volume and tensor-based morphometry was used to elucidate structural brain differences. A triallelic genetic marker resulting from two SLC6A4 promoter region polymorphisms, 5-HTTLPR and rs25531, was analysed for association with MDD and quantitative traits. Results: Healthy controls had a smaller...

  1. Influence of parental care on offspring hippocampal volume in young adults varies as a function of overprotection.

    Science.gov (United States)

    Wang, Yinan; Song, Yiying; Li, Xueting; Zhang, Lin; Liu, Jia

    2017-04-12

    Parental care results in increased hippocampal volumes through adaptive stress responses in developing animals. However, human studies have not yet provided consistent findings analogous to the animal literature, possibly because parental care in humans is likely intermingled with parental overprotection, as suggested by the optimal parenting theory. Here, we tested the hypothesis that the effect of parental care on offspring hippocampal volume varies as a function of parental overprotection with a large cohort of young adult participants (N = 257). Consistent with some previous human studies, we found that parental care in childhood alone had little association with the hippocampal volume in adulthood. However, when parental overprotection was low, parental care was positively correlated with offspring hippocampal volume, whereas there was no association between parental care and offspring hippocampal volume when parental overprotection was high. Thus, an interaction exists between parental care and overprotection in human's hippocampal development, which contributes to the elucidation of the complex relationship between brain structure and environmental factors.

  2. Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood.

    Science.gov (United States)

    Daugherty, Ana M; Flinn, Robert; Ofen, Noa

    2017-06-01

    Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution images in a sample of healthy participants (age 8-25 years). Adults had smaller CA3-dentate gyrus volume as compared to children, which accounted for 67% of the indirect effect of age predicting better associative memory via hippocampal volumes. Whereas hippocampal body volume demonstrated non-linear age differences, larger hippocampal body volume was weakly related to better associative memory only when accounting for the mutual correlation with subfields measured within that region. Thus, typical development of associative memory was largely explained by age-related differences in CA3-dentate gyrus. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Hippocampal volumes among older Indian adults: Comparison with Alzheimer's disease and mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Vikas Dhikav

    2016-01-01

    Full Text Available Background: Hippocampal volume data from India have recently been reported in younger adults. Data in older adults are unknown. The present paper describes hippocampal volume from India among older adults and compares the same with patients having Alzheimer's disease (AD and mild cognitive impairment (MCI. Materials and Methods: A total of 32 cognitively normal subjects, 20 patients with AD, and 13 patients with MCI were enrolled. Patients were evaluated for the diagnosis of AD/MCI using the National Institute of Neurological and Communicative Disorders and Stroke and the Related Disorders Association criteria and the Clinical Dementia Rating (CDR Scale (score = 0.5, respectively. Hippocampal volume was measured using magnetic resonance imaging (MRI machine by manual segmentation (Megnatom Symphony 1.5T scanner three-dimensional (3D sequences. Results: Age and duration of illness in the MCI group were 70.6 ± 8.6 years and 1.9 ± 0.9 years, respectively. In the AD group, age and duration of illness were 72 ± 8.1 years and 3.1 ± 2.2 years, respectively. In cognitively normal subjects, the age range was 45-88 years (66.9 ± 10.32 years. Mean mini–mental status examination (MMSE score of healthy subjects was 28.28 ± 1.33. In the MCI group, MMSE was 27.05 ± 1.79. In the AD group, MMSE was 13.32 ± 5.6. In the healthy group, the hippocampal volume was 2.73 ± 0.53 cm3 on the left side and 2.77 ± 0.6 cm3 on the right side. Likewise, in MCI, the volume on the left side was 2.35 ± 0.42 cm3 and the volume on the right side was 2.36 ± 0.38 cm3. Similarly, in the AD group, the volume on the right side was 1.64 ± 0.55 cm3 and on the left side it was 1.59 ± 0.55 cm3. Post hoc analysis using Tukey's honestly significant difference (HSD showed, using analysis of variance (ANOVA that there was a statistically significant difference between healthy and AD (P ≤ 0.01, and between healthy and MCI (P ≤ 0.01 subjects. There was a correlation between

  4. Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

    Science.gov (United States)

    Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

    2017-09-01

    Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

  5. Insomnia severity is associated with a decreased volume of the CA3/Dentate Gyrus Hippocampal Subfield

    Science.gov (United States)

    Neylan, Thomas C.; Mueller, Susanne G.; Wang, Zhen; Metzler, Thomas J.; Lenoci, Maryann; Truran, Diana; Marmar, Charles R.; Weiner, Michael W.; Schuff, Norbert

    2010-01-01

    Background Prolonged disruption of sleep in animal studies is associated with decreased neurogenesis in the dentate gyrus. Our objective was to determine if insomnia severity in a sample of PTSD and controls was associated with decreased volume in the CA3/dentate hippocampal subfield. Methods Volumes of hippocampal subfields in seventeen veteran males positive for PTSD (41 ±12 years) and nineteen age-matched male veterans negative for PTSD were measured using 4 Tesla MRI. Subjective sleep quality was measured by the Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI). Results Higher scores on the ISI, indicating worse insomnia, were associated with smaller volumes of the CA3/dentate subfields (r= −.48, p < 0.01) in the combined sample. Adding the ISI score as a predictor for CA3/dentate volume to a hierarchical linear regression model after first controlling for age and PTSD symptoms accounted for a 13 % increase in incremental variance (t= −2.47, p= 0.02). Conclusions The findings indicate for the first time in humans that insomnia severity is associated with volume loss of the CA3/dentate subfields. This is consistent with animal studies showing that chronic sleep disruption is associated with decreased neurogenesis and dendritic branching in these structures. PMID:20598672

  6. Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly.

    Science.gov (United States)

    Silbert, Lisa C; Dodge, Hiroko H; Lahna, David; Promjunyakul, Nutta-On; Austin, Daniel; Mattek, Nora; Erten-Lyons, Deniz; Kaye, Jeffrey A

    2016-01-01

    Computer use is becoming a common activity in the daily life of older individuals and declines over time in those with mild cognitive impairment (MCI). The relationship between daily computer use (DCU) and imaging markers of neurodegeneration is unknown. The objective of this study was to examine the relationship between average DCU and volumetric markers of neurodegeneration on brain MRI. Cognitively intact volunteers enrolled in the Intelligent Systems for Assessing Aging Change study underwent MRI. Total in-home computer use per day was calculated using mouse movement detection and averaged over a one-month period surrounding the MRI. Spearman's rank order correlation (univariate analysis) and linear regression models (multivariate analysis) examined hippocampal, gray matter (GM), white matter hyperintensity (WMH), and ventricular cerebral spinal fluid (vCSF) volumes in relation to DCU. A voxel-based morphometry analysis identified relationships between regional GM density and DCU. Twenty-seven cognitively intact participants used their computer for 51.3 minutes per day on average. Less DCU was associated with smaller hippocampal volumes (r = 0.48, p = 0.01), but not total GM, WMH, or vCSF volumes. After adjusting for age, education, and gender, less DCU remained associated with smaller hippocampal volume (p = 0.01). Voxel-wise analysis demonstrated that less daily computer use was associated with decreased GM density in the bilateral hippocampi and temporal lobes. Less daily computer use is associated with smaller brain volume in regions that are integral to memory function and known to be involved early with Alzheimer's pathology and conversion to dementia. Continuous monitoring of daily computer use may detect signs of preclinical neurodegeneration in older individuals at risk for dementia.

  7. Dissociable roles for hippocampal and amygdalar volume in human fear conditioning.

    Science.gov (United States)

    Cacciaglia, Raffaele; Pohlack, Sebastian T; Flor, Herta; Nees, Frauke

    2015-09-01

    Fear conditioning is a basic learning process which involves the association of a formerly neutral conditioned stimulus (CS) with a biologically relevant aversive unconditioned stimulus (US). Previous studies conducted in brain-lesioned patients have shown that while the acquisition of autonomic fear responses requires an intact amygdala, a spared hippocampus is necessary for the development of the CS-US contingency awareness. Although these data have been supported by studies using functional neuroimaging techniques in healthy people, attempts to extend these findings to the morphological aspects of amygdala and hippocampus are missing. Here we tested the hypothesis that amygdalar and hippocampal volumes play dissociable roles in determining autonomic responses and contingency awareness during fear conditioning. Fifty-two healthy individuals (mean age 21.83) underwent high-resolution magnetic resonance imaging. We used a differential delay fear conditioning paradigm while assessing skin conductance responses (SCRs), subjective ratings of CS-US contingency, as well as emotional valence and perceived arousal. Left amygdalar volume significantly predicted the magnitude of differential SCRs during fear acquisition, but had no impact on contingency learning. Conversely, bilateral hippocampal volumes were significantly related to contingency ratings, but not to SCRs. Moreover, left amygdalar volume predicted SCRs to the reinforced CS alone, but not those elicited by the US. Our findings bridge the gap between previous lesion and functional imaging studies, by showing that amygdalar and hippocampal volumes differentially modulate the acquisition of conditioned fear. Further, our results reveal that the morphology of these limbic structures moderate learning and memory already in healthy persons.

  8. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Ericksen Mielle Borba

    2016-12-01

    Full Text Available Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD pathology. Serum brain-derived neurotrophic factor (BDNF reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]. Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  9. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease.

    Science.gov (United States)

    Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, Márcia Lorena Fagundes

    2016-01-01

    Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  10. The MRI study of hippocampal volume and shape in the youth and older

    International Nuclear Information System (INIS)

    Li Yuefeng; Jiang Ping; Tong Xinkang; Wang Dongqing; Peng Weibin; Wei Chuanshe; Yin Ruigen; Zhao Liang; Sun Weibin; Wang Zhengchao

    2009-01-01

    Objective: In the base of the landmarks of the hippocampus identified with neighborhood structures, to measure volumes and shape of normal older age group and youth group's hippocampus and hippocampal head, body, tail. Methods: Thirty younger people (age 20-29 years, youth group) and thirty older people (above 60 years, older age group) were scanned by MR, anatomic landmarks were found, which were constancy and easy to be recognized for segmentation hippocampus. The hippocampal volumes, average areas and number of the hippocampal layer were measured, the interclass data of two groups, different gender and sides were compared with statistics methods of t test and the hippocampal model were made with the three-dimensional reconstruction. Results: All landmarks of 60 subjects could be distinguished clearly, such as uncal recess, triangle of the lateral ventricle, uncal apex et al. The discrepancies of two groups volumes of gender had not statistical significance. The youth groups volumes of left hippocampus, head, body and tail were (1250±174), (653±115), (372±116), (2277±109) mm 3 , and the right were (1255±147), (657±129), (386±105), (2298±213) mm 3 . There was no statistical significance between left and right (t=0.08,0.10,0.33,0.35, P>0.05). The older age groups volumes of left hippocampus, head, body and tail were (660 + 109), (472 -+92), (181 -+73), (1313 + 163) mm 3 ,and the right were (717±116), (474±95), (240±75), (1432±171) mm 3 . Older hippocampal volumes were obviously bigger in right tail than in left (t=2.21, P 0.05). There were manifest statistical significance between two groups left volumes of hippocampus and each parts(t=15.78,6.71,7.70,20.83, P 2 and the right were (73±22), (58±19) mm 2 . Both two groups had manifest statistical significance (t=3.33,2.81, P<0.01). The number of layers of youth and older groups were (11.1± 3.2), (7.9±3.9) layers, and the right were (11.5±3.7), (8.2±3.1) layers. Both two groups had manifest

  11. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease

    OpenAIRE

    Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, M?rcia Lorena Fagundes

    2016-01-01

    Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric me...

  12. Cerebral blood volume alterations during fractional pneumoencephalography

    International Nuclear Information System (INIS)

    Voigt, K.; Greitz, T.

    1976-01-01

    Simultaneous and continuous measurements of the cerebral blood volume (CBV), cerebrospinal fluid (CSF) and blood pressure were carried out in six patients during fractional pneumoencephalography in order to examine intracranial volumetric interactions. Three patients (Group A) showed normal encephalographic findings, and in three patients (Group B) communicating hydrocephalus with convexity block was found encephalographically. In all patients the injection of air was followed by an immediate increase of CSF pressure and blood pressure and a concomitant decrease of CBV. The initial CSF pressure was invariably re-established within 3 to 3.5 min. During this time interval the CBV of the patients of Group B decreased significantly and 30 percent more than that of Group A. Furthermore, after restoration of the original CSF pressure, CBV returned to its initial level in all patients of Group A, whereas it remained unchanged or showed a further decrease in the patients of Group B. Removal of an amount of CSF corresponding to half of the amount of injected air was followed by a significant reactive hyperemic response in two normal patients. The intracranial volumetric alterations during fractional pneumoencephalography are discussed in detail with respect to the underlying physiologic mechanisms and are suggested as a model for acute and low pressure hydrocephalus

  13. Cognitive reserve moderates the association between hippocampal volume and episodic memory in middle age.

    Science.gov (United States)

    Vuoksimaa, Eero; Panizzon, Matthew S; Chen, Chi-Hua; Eyler, Lisa T; Fennema-Notestine, Christine; Fiecas, Mark Joseph A; Fischl, Bruce; Franz, Carol E; Grant, Michael D; Jak, Amy J; Lyons, Michael J; Neale, Michael C; Thompson, Wesley K; Tsuang, Ming T; Xian, Hong; Dale, Anders M; Kremen, William S

    2013-05-01

    Cognitive reserve is hypothesized to help people withstand greater brain pathology without manifesting clinical symptoms, and may be regarded as a preventive factor of dementia. It is unclear whether the effect of cognitive reserve is evident only among the older adults or after conversion to dementia, or if it can also be seen earlier in life before the prominent effects of cognitive aging become apparent. While finding a main effect of cognitive reserve on cognitive outcome may be consistent with the reserve hypothesis, in our view, it is unnecessary to invoke the idea of reserve if only a main effect is present. Rather, it is the interaction between a measure of reserve and a brain measure on cognitive outcome that is key for confirming that the effects of brain pathology affect people differently according to their cognitive reserve. We studied whether general cognitive ability at an average age of 20 years, as a direct measure of cognitive reserve, moderates the association between hippocampal volume and episodic memory performance in 494 middle-aged men ages 51 to 60. Whereas there was no statistically significant direct relationship between hippocampal volume and episodic memory performance in middle age, we found a statistically significant interaction such that there was a positive association between hippocampal volume and episodic memory only among people with lower general cognitive ability at age 20, i.e., lower levels of cognitive reserve. Our results provide support for the hypothesis that cognitive reserve moderates the relationship between brain structure and cognition in middle age, well before the onset of dementia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

    International Nuclear Information System (INIS)

    Zou, Yani; Leu, David; Chui, Jennifer; Fike, John R.; Huang, Ting-Ting

    2013-01-01

    Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted

  15. Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yani [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Leu, David [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Palo Alto Institute of Research and Education, Palo Alto, California (United States); Chui, Jennifer [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Fike, John R. [Departments of Neurosurgery and Radiation Oncology, University of California, San Francisco, California (United States); Huang, Ting-Ting, E-mail: tthuang@stanford.edu [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); VA Palo Alto Health Care System, Palo Alto, California (United States)

    2013-11-15

    Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted.

  16. Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure.

    Science.gov (United States)

    Balaraman, Sridevi; Idrus, Nirelia M; Miranda, Rajesh C; Thomas, Jennifer D

    2017-05-01

    Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol's long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4-9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was attenuated with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p < 0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by

  17. Does white matter structure or hippocampal volume mediate associations between cortisol and cognitive ageing?

    Science.gov (United States)

    Cox, Simon R.; MacPherson, Sarah E.; Ferguson, Karen J.; Royle, Natalie A.; Maniega, Susana Muñoz; Hernández, Maria del C. Valdés; Bastin, Mark E.; MacLullich, Alasdair M.J.; Wardlaw, Joanna M.; Deary, Ian J.

    2015-01-01

    Elevated glucocorticoid (GC) levels putatively damage specific brain regions, which in turn may accelerate cognitive ageing. However, many studies are cross-sectional or have relatively short follow-up periods, making it difficult to relate GCs directly to changes in cognitive ability with increasing age. Moreover, studies combining endocrine, MRI and cognitive variables are scarce, measurement methods vary considerably, and formal tests of the underlying causal hypothesis (cortisol → brain → cognition) are absent. In this study, 90 men, aged 73 years, provided measures of fluid intelligence, processing speed and memory, diurnal and reactive salivary cortisol and two measures of white matter (WM) structure (WM hyperintensity volume from structural MRI and mean diffusivity averaged across 12 major tracts from diffusion tensor MRI), hippocampal volume, and also cognitive ability at age 11. We tested whether negative relationships between cognitive ageing differences (over more than 60 years) and salivary cortisol were significantly mediated by WM and hippocampal volume. Significant associations between reactive cortisol at 73 and cognitive ageing differences between 11 and 73 (r = −.28 to −.36, p cognition associations (cognitive ageing differences from childhood to the early 70s, partly via brain WM structure. PMID:26298692

  18. Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936.

    Directory of Open Access Journals (Sweden)

    Donald M Lyall

    Full Text Available The APOE ε and TOMM40 rs10524523 ('523' variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer's disease (AD related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 '523' genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 '523' poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636. No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1 their specific techniques in adjusting for brain size; 2 assessing more detailed sub-divisions of the hippocampal formation; and 3 testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy.

  19. Depressive Symptom Dimensions and Their Association with Hippocampal and Entorhinal Cortex Volumes in Community Dwelling Older Adults

    Directory of Open Access Journals (Sweden)

    Deirdre M. O’Shea

    2018-02-01

    Full Text Available Objective: Research has shown that depression is a risk factor for Alzheimer’s disease (AD and subsequent cognitive decline. This is compounded by evidence showing an association between depression and reduced hippocampal volumes; a primary structure implicated in the pathogenesis of the disease. Less is known about the relationship between depression and other AD vulnerable regions such as the entorhinal cortex. Given the heterogeneity of depressive symptom presentation, we examined whether symptom dimensions were associated with hippocampal and entorhinal cortex volumes in community dwelling older adults.Methods: Eighty-one community dwelling adults completed the Beck Depression Inventory – second edition and underwent structural neuroimaging. Measures of hippocampal and entorhinal cortex volumes were obtained using FreeSurfer software. Linear regression models included regions of interest as dependent variables, with depressive symptom dimensions, as independent variables, controlling for total intracranial volumes, age, education, and gender.Results: Somatic symptoms were negatively associated with total, right, and left hippocampal volumes. Affective symptoms were negatively associated with total entorhinal cortex volumes, with a marginal main effect on left entorhinal cortex volumes.Conclusion: Our findings provide support for examining depressive symptoms and their association with AD vulnerable regions along subdimensions of affective, cognitive, and somatic symptoms to better understand profiles of symptoms most associated with these regions. Conceptualizing depressive symptoms in this way may also better inform treatment approaches in terms of targeting types of symptoms that may be more closely linked to poorer brain and cognitive health outcomes.

  20. The effects of bilateral vestibular loss on hippocampal volume, neuronal number and cell proliferation in rats

    Directory of Open Access Journals (Sweden)

    Yiwen eZheng

    2012-02-01

    Full Text Available Previous studies in humans have shown that bilateral loss of vestibular function is associated with a significant bilateral atrophy of the hippocampus, which correlated with the patients’ spatial memory deficits. More recently, patients who had recovered from unilateral vestibular neuritis have been reported to exhibit a significant atrophy of the left posterior hippocampus. Therefore, we investigated whether bilateral vestibular deafferentation (BVD would result in a decrease in neuronal number or volume in the rat hippocampus, using stereological methods. At 16 months post-BVD, we found no significant differences in hippocampal neuronal number or volume compared to sham controls, despite the fact that these animals exhibited severe spatial memory deficits. By contrast, using bromodeoxyuridine (BrdU as a marker of cell proliferation, we found that the number of BrdU-labelled cells significantly increased in the dentate gyrus of the hippocampus between 48 h and 1 week following BVD. Although a substantial proportion of these cells survived for up to 1 month, the survival rate was significantly lower in BVD animals when compared with that in sham animals. These results suggest a dissociation between the effects of BVD on spatial memory and hippocampal structure in rats and humans, which cannot be explained by an injury-induced increase in cell proliferation.

  1. The Antiepileptic Ketogenic Diet Alters Hippocampal Transporter Levels and Reduces Adiposity in Aged Rats.

    Science.gov (United States)

    Hernandez, Abbi R; Hernandez, Caesar M; Campos, Keila T; Truckenbrod, Leah M; Sakarya, Yasemin; McQuail, Joseph A; Carter, Christy S; Bizon, Jennifer L; Maurer, Andrew P; Burke, Sara N

    2018-03-14

    Nutritional ketosis is induced by high fat/low carbohydrate dietary regimens, which produce high levels of circulating ketone bodies, shifting metabolism away from glucose utilization. While ketogenic diets (KD) were initially introduced to suppress seizures, they are garnering attention for their potential to treat a myriad of neurodegenerative and metabolic disorders that are associated with advanced age. The feasibility and physiological impact of implementing a long-term KD in old animals, however, has not been systematically examined. In this study, young and aged rats consumed a calorically- and nutritionally-matched KD or control diet for 12 weeks. All KD-fed rats maintained higher levels of BHB and lower levels of glucose relative to controls. However, it took the aged rats longer to reach asymptotic levels of BHB compared to young animals. Moreover, KD-fed rats had significantly less visceral white and brown adipose tissue than controls without a loss of lean mass. Interestingly, the KD led to significant alterations in protein levels of hippocampal transporters for monocarboxylates, glucose, and vesicular glutamate and gamma-aminobutyric acid. Most notably, the age-related decline in vesicular glutamate transporter expression was reversed by the KD. These data demonstrate the feasibility and potential benefits of KDs for treating age-associated neural dysfunction.

  2. Alterations of proliferation and differentiation of hippocampal cells in prenatally stressed rats.

    Science.gov (United States)

    Sun, Hongli; Su, Qian; Zhang, Huifang; Liu, Weimin; Zhang, Huiping; Ding, Ding; Zhu, Zhongliang; Li, Hui

    2015-06-01

    To clarify the alterations of proliferation and differentiation of hippocampal cells in prenatally stressed rats. We investigated the impact of prenatal restraint stress on the hipocampal cell proliferation in the progeny with 5-bromo-2'-deoxyuridine (BrdU), which is a marker of proliferating cells and their progeny. In addition, we observed the differentiation of neural stem cells (NSCs) with double labeling of BrdU/neurofilament (NF), BrdU/glial fibrillary acidic protein (GFAP) in the hipocampus. Prenatal stress (PS) increased cell proliferation in the dentate gyrus (DG) only in female and neuron differentiation of newly divided cells in the DG and CA4 in both male and female. Moreover, the NF and GFAP-positive cells, but not the BrdU-positive cells, BrdU/NF and BrdU/GFAP-positive cells, were found frequently in the CA3 and CA1 in the offspring of each group. These results possibly suggest a compensatory adaptive response to neuronal damage or loss in hippocampus induced by PS. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  3. Mesial temporal lobe epilepsy with hippocampal sclerosis is a network disorder with altered cortical hubs.

    Science.gov (United States)

    Jin, Seung-Hyun; Jeong, Woorim; Chung, Chun Kee

    2015-05-01

    Electrophysiologic hubs within the large-scale functional networks in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) have not been investigated. We hypothesized that mTLE with HS has different resting-state network hubs in their large-scale functional networks compared to the hubs in healthy controls (HC). We also hypothesized that the hippocampus would be a functional hub in mTLE patients with HS. Resting-state functional networks, identified by using magnetoencephalography (MEG) signals in the theta, alpha, beta, and gamma frequency bands, were evaluated. Networks in 44 mTLE patients with HS (left mTLE = 22; right mTLE = 22) were compared with those in 46 age-matched HC. We investigated betweenness centrality at the source-level MEG network. The main network hubs were at the pole of the left superior temporal gyrus in the beta band, the pole of the left middle temporal gyrus in the beta and gamma bands, left hippocampus in the theta and alpha bands, and right posterior cingulate gyrus in all four frequency bands in mTLE patients; all of which were different from the main network hubs in HC. Only patients with left mTLE showed profound differences from HC at the left hippocampus in the alpha band. Our analysis of resting-state MEG signals shows that altered electrophysiologic functional hubs in mTLE patients reflect pathophysiologic brain network reorganization. Because we detected network hubs in both hippocampal and extrahippocampal areas, it is probable that mTLE is a large-scale network disorder rather than a focal disorder. The hippocampus was a network hub in left mTLE but not in right mTLE patients, which may be due to intrinsic functional and structural asymmetries between left and right mTLE patients. The evaluation of cortical hubs, even in the spike-free resting-state, could be a clinical diagnostic marker of mTLE with HS. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  4. Altered intrinsic excitability of hippocampal CA1 pyramidal neurons in aged PDAPP mice

    Directory of Open Access Journals (Sweden)

    Francesco eTamagnini

    2015-10-01

    Full Text Available Amyloidopathy involves the accumulation of insoluble amyloid β (Aβ species in the brain’s parenchyma and is a key histopathological hallmark of Alzheimer’s disease (AD. Work on transgenic mice that overexpress A suggests that elevated A levels in the brain are associated with aberrant epileptiform activity and increased intrinsic excitability of CA1 hippocampal neurons. In this study we examined if similar changes could be observed in hippocampal CA1 pyramidal neurons from aged PDAPP mice (20-23 month old, Indiana mutation: V717F on APP gene compared to their age-matched WT littermate controls. Whole-cell current clamp recordings revealed that sub-threshold intrinsic properties, such as input resistance, resting membrane potential and hyperpolarization activated sag were unaffected, but capacitance was significantly decreased in the transgenic animals. No differences between genotypes were observed in the overall number of action potentials (AP elicited by 500 ms supra-threshold current stimuli. PDAPP neurons, however, exhibited higher instantaneous firing frequencies after accommodation in response to high intensity current injections. The AP waveform was narrower and shorter in amplitude in PDAPP mice: these changes, according to our in silico model of a CA1/3 pyramidal neuron, depended on the respective reduction and increase of Na+ and K+ voltage-gated channels maximal conductances. Finally, the after-hyperpolarization (AHP, seen after the first AP evoked by a +300 pA current injection and after 50 Hz AP bursts, was more pronounced in PDAPP mice.These data show that Aβ-overexpression in aged mice altered the capacitance, the neuronal firing and the AP waveform of CA1 pyramidal neurons. Some of these findings are consistent with previous work on younger PDAPP, they also show important differences that can be potentially ascribed to the interaction between amyloidopathy and ageing. Such a change of IE properties over time

  5. Quantitative analysis of nanoscale intranuclear structural alterations in hippocampal cells in chronic alcoholism via transmission electron microscopy imaging

    Science.gov (United States)

    Sahay, Peeyush; Shukla, Pradeep K.; Ghimire, Hemendra M.; Almabadi, Huda M.; Tripathi, Vibha; Mohanty, Samarendra K.; Rao, Radhakrishna; Pradhan, Prabhakar

    2017-04-01

    Chronic alcoholism is known to alter the morphology of the hippocampus, an important region of cognitive function in the brain. Therefore, to understand the effect of chronic alcoholism on hippocampal neural cells, we employed a mouse model of chronic alcoholism and quantified intranuclear nanoscale structural alterations in these cells. Transmission electron microscopy (TEM) images of hippocampal neurons were obtained, and the degree of structural alteration in terms of mass density fluctuation was determined using the light-localization properties of optical media generated from TEM imaging. The results, which were obtained at length scales ranging from ~30 to 200 nm, show that 10-12 week-old mice fed a Lieber-DeCarli liquid (alcoholic) diet had a higher degree of structural alteration than control mice fed a normal diet without alcohol. The degree of structural alteration became significantly distinguishable at a sample length of ~100 nm, which is the typical length scale of the building blocks of cells, such as DNA, RNA, proteins and lipids. Interestingly, different degrees of structural alteration at such length scales suggest possible structural rearrangement of chromatin inside the nuclei in chronic alcoholism.

  6. Relationship between Interleukin-6 gene polymorphism and hippocampal volume in antipsychotic-naïve schizophrenia: evidence for differential susceptibility?

    Directory of Open Access Journals (Sweden)

    Sunil Vasu Kalmady

    Full Text Available Various lines of evidence including epidemiological, genetic and foetal pathogenetic models suggest a compelling role for Interleukin-6 (IL-6 in the pathogenesis of schizophrenia. IL-6 mediated inflammatory response triggered by maternal infection or stress induces disruption of prenatal hippocampal development which might contribute towards psychopathology during adulthood. There is a substantial lack of knowledge on how genetic predisposition to elevated IL-6 expression effects hippocampal structure in schizophrenia patients. In this first-time study, we evaluated the relationship between functional polymorphism rs1800795 of IL-6 and hippocampal gray matter volume in antipsychotic-naïve schizophrenia patients in comparison with healthy controls.We examined antipsychotic-naïve schizophrenia patients [N = 28] in comparison with healthy controls [N = 37] group matched on age, sex and handedness. Using 3 Tesla - MRI, bilateral hippocampi were manually segmented by blinded raters with good inter-rater reliability using a valid method. Additionally, Voxel-based Morphometry (VBM analysis was performed using hippocampal mask. The IL-6 level was measured in blood plasma using ELISA technique. SNP rs1800795 was genotyped using PCR and DNA sequencing. Psychotic symptoms were assessed using Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms.Schizophrenia patients had significantly deficient left and right hippocampal volumes after controlling for the potential confounding effects of age, sex and total brain volume. Plasma IL-6 levels were significantly higher in patients than controls. There was a significant diagnosis by rs1800795 genotype interaction involving both right and left hippocampal volumes. Interestingly, this effect was significant only in men but not in women.Our first time observations suggest a significant relationship between IL-6 rs1800795 and reduced hippocampal volume in antipsychotic

  7. Posttraumatic Stress Disorder and Depression Symptom Severities Are Differentially Associated With Hippocampal Subfield Volume Loss in Combat Veterans.

    Science.gov (United States)

    Averill, Christopher L; Satodiya, Ritvij M; Scott, J Cobb; Wrocklage, Kristen M; Schweinsburg, Brian; Averill, Lynnette A; Akiki, Teddy J; Amoroso, Timothy; Southwick, Steven M; Krystal, John H; Abdallah, Chadi G

    2017-01-01

    Two decades of human neuroimaging research have associated volume reductions in the hippocampus with posttraumatic stress disorder. However, little is known about the distribution of volume loss across hippocampal subfields. Recent advances in neuroimaging methods have made it possible to accurately delineate 10 gray matter hippocampal subfields. Here, we apply a volumetric analysis of hippocampal subfields to data from a group of combat-exposed Veterans. Veterans (total, n = 68, posttraumatic stress disorder, n = 36; combat control, n = 32) completed high-resolution structural magnetic resonance imaging. Based on previously validated methods, hippocampal subfield volume measurements were conducted using FreeSurfer 6.0. The Clinician-Administered PTSD Scale assessed posttraumatic stress disorder symptom severity; Beck Depression Inventory assessed depressive symptom severity. Controlling for age and intracranial volume, partial correlation analysis examined the relationship between hippocampal subfields and symptom severity. Correction for multiple comparisons was performed using false discovery rate. Gender, intelligence, combat severity, comorbid anxiety, alcohol/substance use disorder, and medication status were investigated as potential confounds. In the whole sample, total hippocampal volume negatively correlated with Clinician-Administered PTSD Scale and Beck Depression Inventory scores. Of the 10 hippocampal subfields, Clinician-Administered PTSD Scale symptom severity negatively correlated with the hippocampus-amygdala transition area (HATA). Beck Depression Inventory scores negatively correlated with dentate gyrus, cornu ammonis 4 (CA4), HATA, CA2/3, molecular layer, and CA1. Follow-up analysis limited to the posttraumatic stress disorder group showed a negative correlation between Clinician-Administered PTSD Scale symptom severity and each of HATA, CA2/3, molecular layer, and CA4. This study provides the first evidence relating posttraumatic stress

  8. The influence of negative life events on hippocampal and amygdala volumes in old age: a life-course perspective

    NARCIS (Netherlands)

    Gerritsen, L.; Kalpouzos, G.; Westman, E.; Simmons, A.; Wahlund, L.O.; Backman, L.; Fratiglioni, L.; Wang, H.X.

    2015-01-01

    Background. Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older

  9. Aluminum alters NMDA receptor 1A and 2A/B expression on neonatal hippocampal neurons in rats

    Directory of Open Access Journals (Sweden)

    Yuan Chia-Yi

    2011-11-01

    Full Text Available Abstract Background High aluminum (Al content in certain infant formula raises the concern of possible Al toxicity on brain development of neonates during their vulnerable period of growing. Results of in vivo study showed that Al content of brain tissues reached to 74 μM when oral intake up to 1110 μM, 10 times of that in the hi-Al infant formula. Methods Utilizing a cultured neuron cells in vitro model, we have assessed Al influence on neuronal specific gene expression alteration by immunoblot and immunohistochemistry and neural proliferation rate changes by MTT assay. Results Microscopic images showed that the neurite outgrowth of hippocampal neurons increased along with the Al dosages (37, 74 μM Al (AlCl3. MTT results also indicated that Al increased neural cell viability. On the other hand, the immunocytochemistry staining suggested that the protein expressions of NMDAR 1A and NMDAR 2A/B decreased with the Al dosages (p Conclusion Treated hippocampal neurons with 37 and 74 μM of Al for 14 days increased neural cell viability, but hampered NMDAR 1A and NMDAR 2A/B expressions. It was suggested that Al exposure might alter the development of hippocampal neurons in neonatal rats.

  10. Aging process alters hippocampal and cortical secretase activities of Wistar rats.

    Science.gov (United States)

    Bertoldi, Karine; Cechinel, Laura Reck; Schallenberger, Bruna; Meireles, Louisiana; Basso, Carla; Lovatel, Gisele Agustini; Bernardi, Lisiane; Lamers, Marcelo Lazzaron; Siqueira, Ionara Rodrigues

    2017-01-15

    A growing body of evidence has demonstrated amyloid plaques in aged brain; however, little attention has been given to amyloid precursor protein (APP) processing machinery during the healthy aging process. The amyloidogenic and non-amyloidogenic pathways, represented respectively by β- and α-secretases (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that the normal aging process could imbalance amyloidogenic and non-amyloidogenic pathways specifically BACE and TACE activities. Besides, although it has been showed that exercise can modulate secretase activities in Alzheimer Disease models the relationship between exercise effects and APP processing during healthy aging process is rarely studied. Our aim was to investigate the aging process and the exercise effects on cortical and hippocampal BACE and TACE activities and aversive memory performance. Young adult and aged Wistar rats were subjected to an exercise protocol (20min/day for 2 weeks) and to inhibitory avoidance task. Biochemical parameters were evaluated 1h and 18h after the last exercise session in order to verify transitory and delayed exercise effects. Aged rats exhibited impaired aversive memory and diminished cortical TACE activity. Moreover, an imbalance between TACE and BACE activities in favor of BACE activity was observed in aged brain. Moderate treadmill exercise was unable to alter secretase activities in any brain areas or time points evaluated. Our results suggest that aging-related aversive memory decline is partly linked to decreased cortical TACE activity. Additionally, an imbalance between secretase activities can be related to the higher vulnerability to neurodegenerative diseases induced by aging. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla Woznica; Vinberg, Maj; Macoveanu, Julian

    2015-01-01

    study assessed the neuroanatomical basis for these effects. METHODS: Patients with TRD who were moderately depressed or BD in partial remission were randomized to 8 weekly EPO (40,000 IU) or saline infusions in a double-blind, parallel-group design. Patients underwent magnetic resonance imaging, memory...... assessment with the Rey Auditory Verbal Learning Test, and mood ratings with the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating Scale at baseline and week 14. Hippocampus segmentation and analysis of hippocampal volume, shape, and gray matter density were conducted...... with FMRIB Software Library tools. Memory change was analyzed with repeated-measures analysis of covariance adjusted for depression symptoms, diagnosis, age, and gender. RESULTS: Eighty-four patients were randomized; 1 patient withdrew and data collection was incomplete for 14 patients; data were thus...

  12. Amount of lifetime video gaming is positively associated with entorhinal, hippocampal and occipital volume.

    Science.gov (United States)

    Kühn, S; Gallinat, J

    2014-07-01

    Playing video games is a popular leisure activity among children and adults, and may therefore potentially influence brain structure. We have previously shown a positive association between probability of gray matter (GM) volume in the ventral striatum and frequent video gaming in adolescence. Here we set out to investigate structural correlates of video gaming in adulthood, as the effects observed in adolescents may reflect only a fraction of the potential neural long-term effects seen in adults. On magnetic resonance imaging (MRI) scans of 62 male adults, we computed voxel-based morphometry to explore the correlation of GM with the lifetime amount of video gaming (termed joystick years). We found a significant positive association between GM in bilateral parahippocamal region (entorhinal cortex) and left occipital cortex/inferior parietal lobe and joystick years (Pvideo game genres played, such as logic/puzzle games and platform games contributing positively, and action-based role-playing games contributing negatively. Furthermore, joystick years were positively correlated with hippocampus volume. The association of lifetime amount of video game playing with bilateral entorhinal cortex, hippocampal and occipital GM volume could reflect adaptive neural plasticity related to navigation and visual attention.

  13. A mid-life vitamin A supplementation prevents age-related spatial memory deficits and hippocampal neurogenesis alterations through CRABP-I.

    Science.gov (United States)

    Touyarot, Katia; Bonhomme, Damien; Roux, Pascale; Alfos, Serge; Lafenêtre, Pauline; Richard, Emmanuel; Higueret, Paul; Pallet, Véronique

    2013-01-01

    Age-related memory decline including spatial reference memory is considered to begin at middle-age and coincides with reduced adult hippocampal neurogenesis. Moreover, a dysfunction of vitamin A hippocampal signalling pathway has been involved in the appearance of age-related memory deficits but also in adult hippocampal neurogenesis alterations. The present study aims at testing the hypothesis that a mid-life vitamin A supplementation would be a successful strategy to prevent age-related memory deficits. Thus, middle-aged Wistar rats were submitted to a vitamin A enriched diet and were tested 4 months later in a spatial memory task. In order to better understand the potential mechanisms mediating the effects of vitamin A supplementation on hippocampal functions, we studied different aspects of hippocampal adult neurogenesis and evaluated hippocampal CRABP-I expression, known to modulate differentiation processes. Here, we show that vitamin A supplementation from middle-age enhances spatial memory and improves the dendritic arborisation of newborn immature neurons probably resulting in a better survival and neuronal differentiation in aged rats. Moreover, our results suggest that hippocampal CRABP-I expression which controls the intracellular availability of retinoic acid (RA), may be an important regulator of neuronal differentiation processes in the aged hippocampus. Thus, vitamin A supplementation from middle-age could be a good strategy to maintain hippocampal plasticity and functions.

  14. Chronic prenatal ethanol exposure alters hippocampal GABA(A) receptors and impairs spatial learning in the guinea pig.

    Science.gov (United States)

    Iqbal, U; Dringenberg, H C; Brien, J F; Reynolds, J N

    2004-04-02

    Chronic prenatal ethanol exposure (CPEE) can injure the developing brain, and may lead to the fetal alcohol syndrome (FAS). Previous studies have demonstrated that CPEE upregulates gamma-aminobutyric acid type A (GABA(A)) receptor expression in the cerebral cortex, and decreases functional synaptic plasticity in the hippocampus, in the adult guinea pig. This study tested the hypothesis that CPEE increases GABA(A) receptor expression in the hippocampus of guinea pig offspring that exhibit cognitive deficits in a hippocampal-dependent spatial learning task. Timed, pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight per day), isocaloric-sucrose/pair-feeding, or water throughout gestation. GABA(A) receptor subunit protein expression in the hippocampus was measured at two development ages: near-term fetus and young adult. In young adult guinea pig offspring, CPEE increased spontaneous locomotor activity in the open-field and impaired task acquisition in the Morris water maze. CPEE did not change GABA(A) receptor subunit protein expression in the near-term fetal hippocampus, but increased expression of the beta2/3-subunit of the GABA(A) receptor in the hippocampus of young adult offspring. CPEE did not change either [(3)H]flunitrazepam binding or GABA potentiation of [(3)H]flunitrazepam binding, but decreased the efficacy of allopregnanolone potentiation of [(3)H]flunitrazepam binding, to hippocampal GABA(A) receptors in adult offspring. Correlational analysis revealed a relationship between increased spontaneous locomotor activity and growth restriction in the hippocampus induced by CPEE. Similarly, an inverse relationship was found between performance in the water maze and the efficacy of allopregnanolone potentiation of [(3)H]flunitrazepam binding in the hippocampus. These data suggest that alterations in hippocampal GABA(A) receptor expression and pharmacological properties contribute to hippocampal-related behavioral and cognitive deficits

  15. Amygdalar and hippocampal volume: A comparison between manual segmentation, Freesurfer and VBM.

    Science.gov (United States)

    Grimm, Oliver; Pohlack, Sebastian; Cacciaglia, Raffaele; Winkelmann, Tobias; Plichta, Michael M; Demirakca, Traute; Flor, Herta

    2015-09-30

    Automated segmentation of the amygdala and the hippocampus is of interest for research looking at large datasets where manual segmentation of T1-weighted magnetic resonance tomography images is less feasible for morphometric analysis. Manual segmentation still remains the gold standard for subcortical structures like the hippocampus and the amygdala. A direct comparison of VBM8 and Freesurfer is rarely done, because VBM8 results are most often used for voxel-based analysis. We used the same region-of-interest (ROI) for Freesurfer and VBM8 to relate automated and manually derived volumes of the amygdala and the hippocampus. We processed a large manually segmented dataset of n=92 independent samples with an automated segmentation strategy (VBM8 vs. Freesurfer Version 5.0). For statistical analysis, we only calculated Pearsons's correlation coefficients, but used methods developed for comparison such as Lin's concordance coefficient. The correlation between automatic and manual segmentation was high for the hippocampus [0.58-0.76] and lower for the amygdala [0.45-0.59]. However, concordance coefficients point to higher concordance for the amygdala [0.46-0.62] instead of the hippocampus [0.06-0.12]. VBM8 and Freesurfer segmentation performed on a comparable level in comparison to manual segmentation. We conclude (1) that correlation alone does not capture systematic differences (e.g. of hippocampal volumes), (2) calculation of ROI volumes with VBM8 gives measurements comparable to Freesurfer V5.0 when using the same ROI and (3) systematic and proportional differences are caused mainly by different definitions of anatomic boundaries and only to a lesser part by different segmentation strategies. This work underscores the importance of using method comparison techniques and demonstrates that even with high correlation coefficients, there can be still large differences in absolute volume. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Preliminary evidence for obesity and elevations in fasting insulin mediating associations between cortisol awakening response and hippocampal volumes and frontal atrophy.

    Science.gov (United States)

    Ursache, Alexandra; Wedin, William; Tirsi, Aziz; Convit, Antonio

    2012-08-01

    Recent studies have demonstrated alterations in the cortisol awakening response (CAR) and brain abnormalities in adults with obesity and type 2 diabetes mellitus (T2DM). While adolescents with T2DM exhibit similar brain abnormalities, less is known about whether brain impairments and hypothalamic-pituitary-adrenal (HPA) axis abnormalities are already present in adolescents with pre-diabetic conditions such as insulin resistance (IR). This study included 33 adolescents with IR and 20 without IR. Adolescents with IR had a blunted CAR, smaller hippocampal volumes, and greater frontal lobe atrophy compared to controls. Mediation analyses indicated pathways whereby a smaller CAR was associated with higher BMI which was in turn associated with fasting insulin levels, which in turn was related to smaller hippocampal volume and greater frontal lobe atrophy. While we had hypothesized that HPA dysregulation may result from brain abnormalities, our findings suggest that HPA dysregulation may also impact brain structures through associations with metabolic abnormalities. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Galanin gene transfer curtails generalized seizures in kindled rats without altering hippocampal synaptic plasticity

    DEFF Research Database (Denmark)

    Kanter-Schlifke, I; Toft Sørensen, Andreas; Ledri, M

    2007-01-01

    . However, it has not been explored whether such treatment can also prevent the epileptogenesis. Using a recombinant adeno-associated viral (rAAV) vector, we induced hippocampal galanin overexpression under the neuron specific enolase promoter in rats. Here we report that in animals with galanin...

  18. BNDF heterozygosity is associated with memory deficits and alterations in cortical and hippocampal EEG power.

    Science.gov (United States)

    Geist, Phillip A; Dulka, Brooke N; Barnes, Abigail; Totty, Michael; Datta, Subimal

    2017-08-14

    Brain derived neurotrophic factor (BDNF) plays a pivotal role in structural plasticity, learning, and memory. Electroencephalogram (EEG) spectral power in the cortex and hippocampus has also been correlated with learning and memory. In this study, we investigated the effect of globally reduced BDNF levels on learning behavior and EEG power via BDNF heterozygous (KO) rats. We employed several behavioral tests that are thought to depend on cortical and hippocampal plasticity to varying degrees: novel object recognition, a test that is reliant on a variety of cognitive systems; contextual fear, which is highly hippocampal-dependent; and cued fear, which has been shown to be amygdala-dependent. We also examined the effects of BDNF reduction on cortical and hippocampal EEG spectral power via chronically implanted electrodes in the motor cortex and dorsal hippocampus. We found that BDNF KO rats were impaired in novelty recognition and fear memory retention, while hippocampal EEG power was decreased in slow waves and increased in fast waves. Interestingly, our results, for the first time, show sexual dimorphism in each of our tests. These results support the hypothesis that BDNF drives both cognitive plasticity and coordinates EEG activity patterns, potentially serving as a link between the two. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Hippocampal volume MRI and 1H-MRS study in chronic alcohol dependent patients

    International Nuclear Information System (INIS)

    Miao Huanmin; Chen Jun; Zha Yunfei; Zhang Yu; Liu Changsheng; Pan Ewu

    2010-01-01

    Objective: To observe the changes of the bilateral hippocampal volume (BHV) and 1 H- MRS appearance of chronic alcohol dependent (CAD) patients and to provide quantitative information for the clinical diagnosis of CAD. Methods: The conventional MR imaging including three-dimensional fast spoiled gradient recalled echo (3D-FSPGR) and 1 H-MRS were performed on 16 patients with CAD (CAD group) and 18 cases of volunteer (control group). The BHV were measured in both groups and the standardized BHV in CAD group and control group were compared. 1 H-MRS metabolites including N-acetylaspartate (NAA), Choline compounds (Cho), Creatine (Cr), and myoinositol (mI) of the bilateral cephalic hippocampus were acquired. The ratios of Cho/Ci, Cho/NAA, NAA/Cr and mI/Ci within the bilateral cephalic hippocampus of the two groups were compared. The t test was used to compare the BHV and the ratios of 1 H-MRS in the bilateral cephalic hippocampus between the two groups. Results: In CAD group, the left and the right hippocampal volume were 1.881±0.292, 2.139±0.328 respectively while they were 2.106±0.245 and 2.267±0.271 respectively in the control group. The BHV had no significant difference between the left and the right in either the CAD group or the control group (t=0.232, 0.147 respectively, P>0.05). The BHV had no significant difference between the CAD group and control group (t=0.424, 0.131 respectively, P>0.05). The Cho/Cr and NAA/Cr in the right cephalic hippocampus of the CAD group were 1.225±0.210 and 1.145±0.034 respectively, while they were 1.429±0.286, 1.612±0.444 respectively in the control group (t=0.321, 0.408, P 1 H-MRS could potentially provide early diagnostic evidence for CAD patients before the onset of cerebral morphological changes. (authors)

  20. Alterations in spatial memory and anxiety in the MAM E17 rat model of hippocampal pathology in schizophrenia.

    Science.gov (United States)

    Gastambide, Francois; Taylor, Amy M; Palmer, Clare; Svard, Heta; Karjalainen, Maija; Janhunen, Sanna K; Tricklebank, Mark; Bannerman, David M

    2015-11-01

    Adult rats exposed to methylazoxymethanol acetate (MAM) at embryonic day 17 (E17) display robust pathological alterations in the hippocampus. However, discrepancies exist in the literature regarding the behavioural effects of this pre-natal manipulation. Therefore, a systematic assessment of MAM E17-induced behavioural alterations was conducted using a battery of dorsal and ventral hippocampus-dependent tests. Compared to saline controls, MAM E17-treated rats displayed deficits in spatial reference memory in both the aversive hidden platform watermaze task and an appetitive Y-maze task. Deficits in the spatial reference memory watermaze task were replicated across three different cohorts and two laboratories. In contrast, there was little, or no, effect on the non-spatial, visible platform watermaze task or an appetitive, non-spatial, visual discrimination task, respectively. MAM rats were also impaired in the spatial novelty preference task which assesses short-term memory, and displayed reduced anxiety levels in the elevated plus maze task. Thus, MAM E17 administration resulted in abnormal spatial information processing and reduced anxiety in a number of hippocampus-dependent behavioural tests, paralleling the effects of dorsal and ventral hippocampal lesions, respectively. These findings corroborate recent pathological and physiological studies, further highlighting the usefulness of MAM E17 as a model of hippocampal dysfunction in at least some aspects of schizophrenia.

  1. Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Tatiana Lauxen Peruzzolo

    2015-01-01

    Full Text Available Pediatric bipolar disorder (PBD is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder. We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm3, respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

  2. Prediction of Treatment Response to Donepezil using Automated Hippocampal Subfields Volumes Segmentation in Patients with Mild Alzheimer's Disease.

    Science.gov (United States)

    Um, Yoo Hyun; Kim, Tae-Won; Jeong, Jong-Hyun; Seo, Ho-Jun; Han, Jin-Hee; Hong, Seung-Chul; Lee, Chang-Uk; Lim, Hyun Kook

    2017-09-01

    Previous studies reported some relationships between donepezil treatment and hippocampus in Alzheimer's disease (AD). However, due to methodological limitations, their close relationships remain unclear. The aim of this study is to predict treatment response to donepezil by utilizing the automated segmentation of hippocampal subfields volumes (ASHS) in AD. Sixty four AD patients were prescribed with donepezil and were followed up for 24 weeks. Cognitive function was measured to assess whether there was a response from the donepezil treatment. ASHS was implemented on non-responder (NR) and responder (TR) groups, and receiver operator characteristic (ROC) analysis was conducted to evaluate the sensitivity, specificity, and accuracy of hippocampal subfields in predicting response to donepezil. The left total hippocampus and the CA1 area of the NR were significantly smaller than those of the TR group. The ROC curve analysis showed the left CA1 volumes showed highest area under curve (AUC) of 0.85 with a sensitivity of 88.0%, a specificity of 74.0% in predicting treatment response to donepezil treatment. We expect that hippocampal subfields volume measurements that predict treatment responses to current AD drugs will enable more evidence-based, individualized prescription of medications that will lead to more favorable treatment outcomes.

  3. Hippocampal volume and auditory attention on a verbal memory task with adult survivors of pediatric brain tumor.

    Science.gov (United States)

    Jayakar, Reema; King, Tricia Z; Morris, Robin; Na, Sabrina

    2015-03-01

    We examined the nature of verbal memory deficits and the possible hippocampal underpinnings in long-term adult survivors of childhood brain tumor. 35 survivors (M = 24.10 ± 4.93 years at testing; 54% female), on average 15 years post-diagnosis, and 59 typically developing adults (M = 22.40 ± 4.35 years, 54% female) participated. Automated FMRIB Software Library (FSL) tools were used to measure hippocampal, putamen, and whole brain volumes. The California Verbal Learning Test-Second Edition (CVLT-II) was used to assess verbal memory. Hippocampal, F(1, 91) = 4.06, ηp² = .04; putamen, F(1, 91) = 11.18, ηp² = .11; and whole brain, F(1, 92) = 18.51, ηp² = .17, volumes were significantly lower for survivors than controls (p memory indices of auditory attention list span (Trial 1: F(1, 92) = 12.70, η² = .12) and final list learning (Trial 5: F(1, 92) = 6.01, η² = .06) were significantly lower for survivors (p auditory attention, but none of the other CVLT-II indices. Secondary analyses for the effect of treatment factors are presented. Volumetric differences between survivors and controls exist for the whole brain and for subcortical structures on average 15 years post-diagnosis. Treatment factors seem to have a unique effect on subcortical structures. Memory differences between survivors and controls are largely contingent upon auditory attention list span. Only hippocampal volume is associated with the auditory attention list span component of verbal memory. These findings are particularly robust for survivors treated with radiation. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  4. Correlated alterations in serotonergic and dopaminergic modulations at the hippocampal mossy fiber synapse in mice lacking dysbindin.

    Directory of Open Access Journals (Sweden)

    Katsunori Kobayashi

    Full Text Available Dysbindin-1 (dystrobrevin-binding protein 1, DTNBP1 is one of the promising schizophrenia susceptibility genes. Dysbindin protein is abundantly expressed in synaptic regions of the hippocampus, including the terminal field of the mossy fibers, and this hippocampal expression of dysbindin is strongly reduced in patients with schizophrenia. In the present study, we examined the functional role of dysbindin in hippocampal mossy fiber-CA3 synaptic transmission and its modulation using the sandy mouse, a spontaneous mutant with deletion in the dysbindin gene. Electrophysiological recordings were made in hippocampal slices prepared from adult male sandy mice and their wild-type littermates. Basic properties of the mossy fiber synaptic transmission in the mutant mice were generally normal except for slightly reduced frequency facilitation. Serotonin and dopamine, two major neuromodulators implicated in the pathophysiology of schizophrenia, can potentiate mossy fiber synaptic transmission probably via an increase in cAMP levels. Synaptic potentiation induced by serotonin and dopamine was very variable in magnitude in the mutant mice, with some mice showing prominent enhancement as compared with the wild-type mice. In addition, the magnitude of potentiation induced by these monoamines significantly correlated with each other in the mutant mice, indicating that a subpopulation of sandy mice has marked hypersensitivity to both serotonin and dopamine. While direct activation of the cAMP cascade by forskolin induced robust synaptic potentiation in both wild-type and mutant mice, this forskolin-induced potentaition correlated in magnitude with the serotonin-induced potentiation only in the mutant mice, suggesting a possible change in coupling of receptor activation to downstream signaling. These results suggest that the dysbindin deficiency could be an essential genetic factor that causes synaptic hypersensitivity to dopamine and serotonin. The altered

  5. A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

    Directory of Open Access Journals (Sweden)

    Erica L. Underwood

    2016-01-01

    Full Text Available While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms.

  6. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Katrina, E-mail: Trinabena23@gmail.com; Lenards, Nishele; Holson, Janice

    2016-04-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

  7. Childhood poverty is associated with altered hippocampal function and visuospatial memory in adulthood

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Duval

    2017-02-01

    Full Text Available Childhood poverty is a risk factor for poorer cognitive performance during childhood and adulthood. While evidence linking childhood poverty and memory deficits in adulthood has been accumulating, underlying neural mechanisms are unknown. To investigate neurobiological links between childhood poverty and adult memory performance, we used functional magnetic resonance imaging (fMRI during a visuospatial memory task in healthy young adults with varying income levels during childhood. Participants were assessed at age 9 and followed through young adulthood to assess income and related factors. During adulthood, participants completed a visuospatial memory task while undergoing MRI scanning. Patterns of neural activation, as well as memory recognition for items, were assessed to examine links between brain function and memory performance as it relates to childhood income. Our findings revealed associations between item recognition, childhood income level, and hippocampal activation. Specifically, the association between hippocampal activation and recognition accuracy varied as a function of childhood poverty, with positive associations at higher income levels, and negative associations at lower income levels. These prospective findings confirm previous retrospective results detailing deleterious effects of childhood poverty on adult memory performance. In addition, for the first time, we identify novel neurophysiological correlates of these deficits localized to hippocampus activation.

  8. Childhood poverty is associated with altered hippocampal function and visuospatial memory in adulthood.

    Science.gov (United States)

    Duval, Elizabeth R; Garfinkel, Sarah N; Swain, James E; Evans, Gary W; Blackburn, Erika K; Angstadt, Mike; Sripada, Chandra S; Liberzon, Israel

    2017-02-01

    Childhood poverty is a risk factor for poorer cognitive performance during childhood and adulthood. While evidence linking childhood poverty and memory deficits in adulthood has been accumulating, underlying neural mechanisms are unknown. To investigate neurobiological links between childhood poverty and adult memory performance, we used functional magnetic resonance imaging (fMRI) during a visuospatial memory task in healthy young adults with varying income levels during childhood. Participants were assessed at age 9 and followed through young adulthood to assess income and related factors. During adulthood, participants completed a visuospatial memory task while undergoing MRI scanning. Patterns of neural activation, as well as memory recognition for items, were assessed to examine links between brain function and memory performance as it relates to childhood income. Our findings revealed associations between item recognition, childhood income level, and hippocampal activation. Specifically, the association between hippocampal activation and recognition accuracy varied as a function of childhood poverty, with positive associations at higher income levels, and negative associations at lower income levels. These prospective findings confirm previous retrospective results detailing deleterious effects of childhood poverty on adult memory performance. In addition, for the first time, we identify novel neurophysiological correlates of these deficits localized to hippocampus activation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

    KAUST Repository

    Baud, Maxime O.

    2016-05-03

    © 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment.

  10. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure.

    Science.gov (United States)

    Baud, Maxime O; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J; Petit, Jean-Marie

    2016-10-01

    Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment. © 2016 European Sleep Research Society.

  11. Major depressive episodes over the course of 7 years and hippocampal subfield volumes at 7 tesla MRI: the PREDICT-MR study.

    Science.gov (United States)

    Wisse, L E M; Biessels, G J; Stegenga, B T; Kooistra, M; van der Veen, P H; Zwanenburg, J J M; van der Graaf, Y; Geerlings, M I

    2015-04-01

    Smaller hippocampal volumes have been associated with major depressive disorder (MDD). The hippocampus consists of several subfields that may be differentially related to MDD. We investigated the association of occurrence of major depressive episodes (MDEs), assessed five times over seven years, with hippocampal subfield and entorhinal cortex volumes at 7 tesla MRI. In this prospective study of randomly selected general practice attendees, MDEs according to DSM-IV-R criteria were assessed at baseline and after 6, 12, 39 and 84 months follow-up. At the last follow-up, a T2 (0.7 mm(3)) 7 tesla MRI scan was obtained in 47 participants (60±10 years). The subiculum, cornu ammonis (CA) 1 to 3, dentate gyrus&CA4 and entorhinal cortex volumes were manually segmented according a published protocol. Of the 47 participants, 13 had one MDE and 5 had multiple MDEs. ANCOVAs, adjusted for age, sex, education and intracranial volume, revealed no significant differences in hippocampal subfield or entorhinal cortex volumes between participants with and without an MDE in the preceding 84 months. Multiple episodes were associated with smaller subiculum volumes (B=-0.03 mL/episode; 95% CI -0.06; -0.003), but not with the other hippocampal subfield volumes, entorhinal cortex, or total hippocampal volume. A limitation of this study is the small sample size which makes replication necessary. In this exploratory study, we found that an increasing number of major depressive episodes was associated with smaller subiculum volumes in middle-aged and older persons, but not with smaller volumes in other hippocampal subfields or the entorhinal cortex. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Abrogation of Early Apoptosis Does Not Alter Late Inhibition of Hippocampal Neurogenesis After Irradiation

    International Nuclear Information System (INIS)

    Li Yuqing; Aubert, Isabelle; Wong, C. Shun

    2010-01-01

    Purpose: Irradiation of the adult brain results in acute apoptosis of neural progenitors and vascular endothelial cells, as well as late dysfunction of neural progenitors and inhibition of neurogenesis. We sought to determine whether the early apoptotic response has a causative role in late inhibition of neurogenesis after cranial irradiation. Methods and Materials: Using a genetic approach with p53 and smpd1 transgenic mice and a pharmacologic approach with basic fibroblast growth factor (bFGF) to abrogate the early apoptotic response, we evaluated the late inhibition of neurogenesis in the hippocampal dentate gyrus after cranial irradiation. Results: In dentate gyrus, subgranular neural progenitors underwent p53-dependent apoptosis within 24 h after irradiation. Despite a near abrogation of neural progenitor apoptosis in p53-/- mice, the reduction in newborn neurons in dentate gyrus at 9 weeks after irradiation in p53-/- mice was not different from that observed in wildtype controls. Endothelial cell apoptosis after radiation is mediated by membrane damage initiated by activation of acid sphingomyelinase (ASMase). Deletion of the smpd1 gene (which encodes ASMase) attenuated the apoptotic response of endothelial cells. At 9 weeks after irradiation, the inhibition of hippocampal neurogenesis was not rescued by ASMase deficiency. Intravenous administration of bFGF protected both endothelial cells and neural progenitors against radiation-induced apoptosis. There was no protection against inhibition of neurogenesis at 9 weeks after irradiation in bFGF-treated mice. Conclusion: Early apoptotic death of neural progenitors, endothelial cells, or both does not have a causative association with late inhibition of neurogenesis after irradiation.

  13. Visit-to-Visit Blood Pressure Variability in Young Adulthood and Hippocampal Volume and Integrity at Middle Age: The CARDIA Study (Coronary Artery Risk Development in Young Adults).

    Science.gov (United States)

    Yano, Yuichiro; Reis, Jared P; Levine, Deborah A; Bryan, R Nick; Viera, Anthony J; Shimbo, Daichi; Tedla, Yacob G; Allen, Norrina B; Schreiner, Pamela J; Bancks, Michael P; Sidney, Stephen; Pletcher, Mark J; Liu, Kiang; Greenland, Philip; Lloyd-Jones, Donald M; Launer, Lenore J

    2017-12-01

    The aims of this study are to assess the relationships of visit-to-visit blood pressure (BP) variability in young adulthood to hippocampal volume and integrity at middle age. We used data over 8 examinations spanning 25 years collected in the CARDIA study (Coronary Artery Risk Development in Young Adults) of black and white adults (age, 18-30 years) started in 1985 to 1986. Visit-to-visit BP variability was defined as by SD BP and average real variability (ARV BP , defined as the absolute differences of BP between successive BP measurements). Hippocampal tissue volume standardized by intracranial volume (%) and integrity assessed by fractional anisotropy were measured by 3-Tesla magnetic resonance imaging at the year-25 examination (n=545; mean age, 51 years; 54% women and 34% African Americans). Mean systolic BP (SBP)/diastolic BP levels were 110/69 mm Hg at year 0 (baseline), 117/73 mm Hg at year 25, and ARV SBP and SD SBP were 7.7 and 7.9 mm Hg, respectively. In multivariable-adjusted linear models, higher ARV SBP was associated with lower hippocampal volume (unstandardized regression coefficient [standard error] with 1-SD higher ARV SBP : -0.006 [0.003]), and higher SD SBP with lower hippocampal fractional anisotropy (-0.02 [0.01]; all P young adulthood may be useful in assessing the potential risk for reductions in hippocampal volume and integrity in midlife. © 2017 American Heart Association, Inc.

  14. Systematic comparison of different techniques to measure hippocampal subfield volumes in ADNI2

    DEFF Research Database (Denmark)

    Mueller, Susanne G.; Yushkevich, Paul A.; Das, Sandhitsu

    2018-01-01

    labeling techniques in a sub-set of the ADNI2 population. Methods The high resolution T2 weighted hippocampal images (T2-HighRes) and the corresponding T1 images from 106 ADNI2 subjects (41 controls, 57 MCI, 8 AD) were processed as follows. A. T1-based: 1. Freesurfer + Large......Objective Subfield-specific measurements provide superior information in the early stages of neurodegenerative diseases compared to global hippocampal measurements. The overall goal was to systematically compare the performance of five representative manual and automated T1 and T2 based subfield...... regression analyses were used to calculate effect sizes (ES) for group, amyloid positivity in controls, and associations with cognitive/memory performance for each approach. Results Subfield volumetry was better than whole hippocampal volumetry for the detection of the mild atrophy differences between...

  15. Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes.

    Science.gov (United States)

    Possin, Katherine L; Kim, Hosung; Geschwind, Michael D; Moskowitz, Tacie; Johnson, Erica T; Sha, Sharon J; Apple, Alexandra; Xu, Duan; Miller, Bruce L; Finkbeiner, Steven; Hess, Christopher P; Kramer, Joel H

    2017-07-01

    Our brains represent spatial information in egocentric (self-based) or allocentric (landmark-based) coordinates. Rodent studies have demonstrated a critical role for the caudate in egocentric navigation and the hippocampus in allocentric navigation. We administered tests of egocentric and allocentric working memory to individuals with premotor Huntington's disease (pmHD), which is associated with early caudate nucleus atrophy, and controls. Each test had 80 trials during which subjects were asked to remember 2 locations over 1-sec delays. The only difference between these otherwise identical tests was that locations could only be coded in self-based or landmark-based coordinates. We applied a multiatlas-based segmentation algorithm and computed point-wise Jacobian determinants to measure regional variations in caudate and hippocampal volumes from 3T MRI. As predicted, the pmHD patients were significantly more impaired on egocentric working memory. Only egocentric accuracy correlated with caudate volumes, specifically the dorsolateral caudate head, right more than left, a region that receives dense efferents from dorsolateral prefrontal cortex. In contrast, only allocentric accuracy correlated with hippocampal volumes, specifically intermediate and posterior regions that connect strongly with parahippocampal and posterior parietal cortices. These results indicate that the distinction between egocentric and allocentric navigation applies to working memory. The dorsolateral caudate is important for egocentric working memory, which can explain the disproportionate impairment in pmHD. Allocentric working memory, in contrast, relies on the hippocampus and is relatively spared in pmHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Altered Volume and Functional Connectivity of the Habenula in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2017-12-01

    Full Text Available The pathogenesis of schizophrenia (SCH is associated with the dysfunction of monoamine neurotransmitters, the synthesis and release of which are mainly regulated by a key structure, the habenular (Hb nucleus. However, little is known regarding whether SCH is associated with structural or functional alterations in the Hb. In this study, we combined structural and resting-state functional magnetic resonance imaging to investigate the changes in volume and functional connectivity of the Hb in 15 patients with SCH vs. 16 age- and gender-matched healthy controls (HCs. Morphologically, the absolute volume of the bilateral Hb was significantly lower in the SCH patients than in the HCs. Functionally, the bilateral Hb showed significantly enhanced functional connectivity with the left medial prefrontal cortex (mPFC in the SCH patients. Additionally, the SCH patients exhibited increased functional connectivity of the left Hb with the left lingual gyrus and right inferior frontal gyrus (IFG. A further exploratory analysis revealed that the SCH patients showed increased functional connectivity between the right Hb and several subcortical regions related to dopaminergic pathways, including the left ventral striatum, caudate and putamen. Finally, the increased functional connectivity of the right Hb with the mPFC was positively correlated with the Brief Psychiatric Rating Scale (BPRS scores in the patients. Together, these results suggest that the altered volume and functional connectivity of the Hb may be involved in the pathogenesis of SCH and thus that the Hb may serve as a potential target in developing new therapeutic strategies in SCH.

  17. Impaired cognitive function and altered hippocampal synapse morphology in mice lacking Lrrtm1, a gene associated with schizophrenia.

    Directory of Open Access Journals (Sweden)

    Noriko Takashima

    Full Text Available Recent genetic linkage analysis has shown that LRRTM1 (Leucine rich repeat transmembrane neuronal 1 is associated with schizophrenia. Here, we characterized Lrrtm1 knockout mice behaviorally and morphologically. Systematic behavioral analysis revealed reduced locomotor activity in the early dark phase, altered behavioral responses to novel environments (open-field box, light-dark box, elevated plus maze, and hole board, avoidance of approach to large inanimate objects, social discrimination deficit, and spatial memory deficit. Upon administration of the NMDA receptor antagonist MK-801, Lrrtm1 knockout mice showed both locomotive activities in the open-field box and responses to the inanimate object that were distinct from those of wild-type mice, suggesting that altered glutamatergic transmission underlay the behavioral abnormalities. Furthermore, administration of a selective serotonin reuptake inhibitor (fluoxetine rescued the abnormality in the elevated plus maze. Morphologically, the brains of Lrrtm1 knockout mice showed reduction in total hippocampus size and reduced synaptic density. The hippocampal synapses were characterized by elongated spines and diffusely distributed synaptic vesicles, indicating the role of Lrrtm1 in maintaining synaptic integrity. Although the pharmacobehavioral phenotype was not entirely characteristic of those of schizophrenia model animals, the impaired cognitive function may warrant the further study of LRRTM1 in relevance to schizophrenia.

  18. State-dependent alterations in hippocampal oscillations in serotonin 1A receptor-deficient mice.

    Science.gov (United States)

    Gordon, Joshua A; Lacefield, Clay O; Kentros, Clifford G; Hen, Rene

    2005-07-13

    Mice lacking the serotonin 1A receptor (5-HT(1A)R) show increased levels of anxiety-related behavior across multiple tests and background strains. Tissue-specific rescue experiments, lesion studies, and neurophysiological findings all point toward the hippocampus as a potential mediator of the phenotype. Serotonin, acting through 5-HT(1A)Rs, can suppress hippocampal theta-frequency oscillations, suggesting that theta oscillations might be increased in the knock-outs. To test this hypothesis, local field potential recordings were obtained from the hippocampus of awake, behaving knock-outs and wild-type littermates. The magnitude of theta oscillations was increased in the knock-outs, specifically in the anxiety-provoking elevated plus maze and not in a familiar environment or during rapid eye movement sleep. Theta power correlated with the fraction of time spent in the open arms, an anxiety-related behavioral variable. These results suggest a possible role for the hippocampus, and theta oscillations in particular, in the expression of anxiety in 5-HT(1A)R-deficient mice.

  19. Long-term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation

    Directory of Open Access Journals (Sweden)

    Celia J A Morgan

    2014-12-01

    Full Text Available Ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, is rising in popularity as a drug of abuse. Preliminary evidence suggests that chronic, heavy ketamine use may have profound effects on spatial memory but the mechanism of these deficits is as yet unclear. This study aimed to examine the neural mechanism by which heavy ketamine use impairs spatial memory processing. In a sample of 11 frequent ketamine users and 15 polydrug controls, matched for IQ, age and years in education. We used fMRI utilising an ROI approach to examine the neural activity of three regions known to support successful navigation; the hippocampus, parahippocampal gyrus and the caudate nucleus during a virtual reality task of spatial memory. Frequent ketamine users displayed spatial memory deficits, accompanied by and related to, reduced activation in both the right hippocampus and left parahippocampal gyrus during navigation from memory, and in the left caudate during memory updating, compared to controls. Ketamine users also exhibited schizotypal and dissociative symptoms that were related to hippocampal activation. Impairments in spatial memory observed in ketamine users are related to changes in medial temporal lobe activation. Disrupted medial temporal lobe function may be a consequence of chronic ketamine abuse and may relate to schizophrenia-like symptomatology observed in ketamine users.

  20. Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume

    NARCIS (Netherlands)

    Carmichael, Owen; Xie, Jing; Fletcher, Evan; Singh, Baljeet; Decarli, Charles; A, Saradha; Abdi, Hervé; Abdul Hadi, Normi; Abdulkadir, Ahmed; Abdullah, Afnizanfaizal; Achuthan, Anusha; Adluru, Nagesh; Aggarwal, Namita; Aghajanian, Jania; Agyemang, Alex; Ahdidan, Jamila; Ahmad, Duaa; Ahmed, Shiek; Ahmed, Fareed; Ahmed, Fayeza; Akbarifar, Roshanak; Akhondi-Asl, Alireza; Aksu, Yaman; Alcauter, Sarael; Daniel, Alexander; Alin, Aylin; Alshuft, Hamza; Alvarez-Linera, Juan; Amin-Mansour, Ali; Anderson, Dallas; Anderson, Jeff; Andorn, Anne; Ang, Amma; Angersbach, Steve; Ansarian, Reza; Appaji, Abhishek; Appannah, Arti; Arfanakis, Konstantinos; Armentrout, Steven; Arrighi, Michael; Arumughababu, S. Vethanayaki; Arunagiri, Vidhya; Ashe-McNalley, Cody; Ashford, Wes; Aurelie, Le Page; Avants, Brian; Aviv, Richard; Avula, Ramesh; Ayache, Nicholas; Ayan-Oshodi, Mosun; Ayhan, Murat; B V, Sumana; Babic, Tomislav; Bach Cuadra, Meritxell; Bagepally, Bhavani; Baird, Geoffrey; Baker, John; Baker, Suzanne; Bakker, Arnold; Baladandayuthapani, Veerabhadran; Barbash, Shahar; Barker, Warren; Bartlett, Jonathan; Bartley, Mairead; Baruchin, Andrea; Battaglini, Iacopo; Bauer, Corinna; Bayley, Peter; Beck, Irene; Becker, James; Beckett, Laurel; Bednar, Martin; Bedner, Arkadiusz; Beg, Mirza Faisal; Bekris, Lynn; Belaroussi, Boubakeur; Belloch, Vicente; Ben Ahmed, Olfa; Bender, J. Dennis; Bendib, Mohamed Mokhtar; Benois-Pineau, Jenny; Bhagchandani, Sameer; Bienkowska, Katarzyna; Biffi, Alessandro; Bilgic, Basar; Bilgin, Gokhan; Billing, Bill; Bishop, Courtney; Bittner, Daniel; Björnsdotter, Malin; Black, Sandra; Bloss, Cinnamon; Blunck, Yasmin; Bocti, Christian; Bohorquez, Adriana; Bokde, Arun; Boone, John; Borrie, Michael; Bourgeat, Pierrick; Bouttout, Haroune; Bowman, DuBois; Gene, Gene; Boxer, Adam; Bozoki, Andrea; Bracard, Serge; Braskie, Meredith; Braunewell, Karl; Breitner, Joihn; Bresell, Anders; Brewer, James; Brickhouse, Michael; Brickman, Adam; Britschgi, Markus; Broadbent, Steve; Brock, Birgitte; Buchsbaum, Monte; Buerger, Katharina; Bunce, David; Burnham, Samantha; Burns, Jeffrey; Burzykowski, Tomasz; Butler, Tracy; Cabeza, Rafael; Cabral, George; Caffery, Terrell; Cai, Zhengchen; Callhoff, Johanna; Calvini, Piero; Campbell, Noll; Carbotti, Angela; Carle, Adam; Carmasin, Carle; Carpenter, Carmichael; Carvalho, Janessa; Casanova, Casanova Ramon; Casey, Anne; David, David; Cash, David; Cataldo, Rosella; Cella, Massimo; Chakravarty, Mallar; Chang, Ih; Chao, Linda; Charil, Arnaud; Che-Wei, Chang; Chen, Kewei; Chen, Shuzhong; Chen, Ing-jou; Chen, Jung-Tai; Chen, Rong; Chen, Chuangquan; Chen, Qiang; Chen, Heng; Chen, Jake; Chen, Gang; Cheng, Wei-Chen; Cheng, Xi; Cheng, Bo; Cherkas, Yauheniya; Chertkow, Howard; Cheung, Vinci; Chiang, Gloria; Chiao, Ping; chibane, Mouatez Billah; Chida, Noriko; Chin, Simon; Ching, Christopher; Chisholm, Jane; Cho, Claire; Cho, Sung-Sik; Choe, John; Choubey, Suresh; Chowbina, Sudhir; Ciocia, Gianluigi; Clark, David; Clarkson, Matt; Clerc, Stephanie; Climer, Sharlee; Clunie, David; Coen, Michael; Coimbra, Alexandre; Compton, David; Coubard, Olivier; Coulin, Samuel; Coulson, Elizabeth; Cover, Keith S.; Crans, Gerald; Crawford, Karen; Croop, Robert; Crum, William; Cui, Yue; Da, Long; Daiello, Lori; Darby, Eveleen; Darkner, Sune; Darnell, Robert; Davatzikos, Christos; DavidPrakash, Bhaskaran; Davidson, Christopher; Davis, Melissa; de Bruijne, Marleen; Decker, Summer; DeDuck, Kristina; Dehghan, Hossein; Della Rosa, Pasquale Anthony; DeOrchis, Vincent; Dépy Carron, Delphine; Desjardins, Benoit; deToledo-Morrell, Leyla; Devanand, Davangere; Devanarayan, Viswanath; Devier, Deidre; DeVous, Michael; Di, Xin; Di, Jianing; Diaz-Arrastia, Ramon; Diciotti, Stefano; Dickerson, Bradford; Dickie, David Alexander; Dickinson, Philip; Dill, Vanderson; Ding, Xiaobo; Dinov, Ivo; Dobosh, Brian; Dobson, Howard; Dodge, Hiroko; Dolman, Andrew; Dolmo, Bess-Carolina; Dong, Wen; Donohue, Michael; Dore, Vincent; Dorflinger, Ernest; Dowling, Maritza; Dragicevic, Natasa; Dubal, Dena; Duchesne, Simon; Duff, Kevin; Dukart, Jürgen; Durazzo, Timothy; Dutta, Joyita; DWors, Robert; Egefjord, Lærke; Elcoroaristizabal, Xabier; Emahazion, Tesfai; Endres, Christopher; Epstein, Noam; Ereshefsky, Larry; Eskildsen, Simon; Espinosa, Eskildsen; Esposito, Mario; Ewers, Michael; Falcone, Guido; Fan, Zhen; Fan, Yong; Fan, Jing; Fang, Zheng; Farahibozorg, Seyedehrezvan; Farahmandpoor, Zeinab; Farb, Norman; Fardo, David; Farias, Sarah; Farnum, Michael; Farrer, Lindsay; Fatke, Bastian; Faux, Noel; Favilla, Stefania; Fazlollahi, Amir; Feldman, Betsy; Félix, Zandra; Fennema-Notestine, Christine; Fernandes, Michel; Fernandez, Santos; Fernandez, Elsa; Ferrer, Eugene; Fetterman, Bob; Figurski, Michal; Fillit, Howard; Finch, Stephen; Fiot, Jean-Baptiste; Flenniken, Derek; Flores, Christopher; Flynn Longmire, Crystal; Focke, Niels; Forsythe, Alan; Foxhall, Suzanne; Franko, Edit; Freeman, Roderick; Freire, Rodolpho; Friedrich, Christoph M.; Friesenhahn, Michel; Giovanni, Giovanni; Fritzsche, Klaus; Fujiwara, Ken; Fullerton, Terence; Gaffour, Yacine; Galvin, Ben; Gamst, Anthony; Gan, Ke; Gao, Sujuan; Garg, Gaurav; Gaser, Christian; Gastineau, Edward; Gattaz, Wagner; Gaubert, Malo; Gaudreau, Amanda; Gauthier, Serge; Ge, Tian; Gemme, Gianluca; Geraci, Joseph; Gholipour, Farhad; Ghosh, Debashis; Ghosh, Satrajit; Gieschke, Ronald; Gill, Ryan; Gillespie, William; Gitelman, Darren; Gkontra, Xenia; Gleason, Carey; Glymour, M. Maria; Godbey, Michael; Gold, Brian; Goldberg, Terry; Goldman, Jennifer; Gomar, Jesus; Gonzalez-Beltran, Alejandra; Gore, Chris; Gorriz, Juan Manuel; Goto, Masami; Gradkowski, Wojciech; Grasela, Thaddeus; Gray, Katherine; Gregory, Erik; Greicius, Michael; Grill, Joshua; Grolmusz, Vince; Gross, Alden; Gross, Alan; Grydeland, Håkon; Guignot, Isabelle; Guo, Hongbin; Guo, Gimiao; Guo, Liang-Hao; Gupta, Vinay; Guyot, Jennifer; Haas, Magali; Habeck, Christian; Habte, Frezghi; Haight, Thaddeus; Hajaj, Chen; Hajiesmaeili, Maryam; Hajjar, Ihab; Hammarstrom, Per; Hampel, Harald; Han, Zhaoying; Han, Duke; Hanna, Yousef; Hanna-Pladdy, Brenda; Hao, Yongfu; Hardy, Peter; Harrison, John; Harvey, Danielle; Hayashi, Toshihiro; Haynes, John-Dylan; He, Yong; He, Huiguang; Head, Denise; Heckemann, Rolf; Heegaard, Niels; Heidebrink, Judith; Hellyer, Peter; Helwig, Michael; Henderson, David; Herholz, Karl; Hess, Christopher; Hill, Sophie; Hisaka, Akihiro; Ho Ming, Au Yeung; Hobart, Jeremy; Hochstetler, Helen; Hofer, Scott; Hoffman, John; Holder, Daniel; Hollingworth, Paul; Holmes, Robin; Hong, Hyunseok; Hong, Hong; Honigberg, Lee; Hoogenraad, Frank; Hope, Thomas; Hot, Pascal; Hsieh, Helen; Hsu, Ailing; Hu, William; Hu, Xiaochen; Hu, Chenhui; Hu, Mingxing; Hua, Wen-Yu; Huang, Chien-Chih; Huang, Xudong; Huang, Juebin; Huang, Yifan; Huang, Chun-Jung; Huang, Zihan; Huentelman, Matthew; Huppertz, Hans-Jürgen; Hurt, Stephen; Hussain, Maqbool; Hutchins, Jim; Hwang, Scott; Hyun, JungMoon; Ifeachor, Emmanuel; Iglesias, Martina; Ikonomidou, Vasiliki; Iman, Adjoudj; Imani, Farzin; Immermann, Fred; Inlow, Mark; Inoue, Lurdes; Insel, Philip; Irizarry, Michael; Ishibashi, Taro; Ishii, Kenji; Ito, Kaori; Iwatsubo, Takeshi; Jacks, Adam; Jacobson, Mark; Jacqmin, Philippe; Jaeger, Markus; Jagger, Richard; Jagust, William; Janousova, Eva; Jara, Hernan; Jedynak, Bruno; Jefferson, Angela; Jenq, John; Jiang, Tianzi; Jiang, Chunxiang; Jiao, Yun; Jiaolong, Qin; Jin, Kun; Johnson, Sterling; Johnson, Julene; Johnson, Kent; Gareth, Gareth; Jones, Mark; Jones, Richard; Joshi, Rohit; Joshi, Shantanu; Jouvent, Eric; Juengling, Freimut; Jung, Wonbeom; Junjie, Zhuo; K G, Muthamma; Kabilan, Meena; Kairui, Zhang; Kam, Hye Jin; Kamer, Angela; Kanakaraj, Sithara; Kanchev, Vladimir; Kaneko, Tomoki; Kaneta, Tomohiro; Kang, Hyunseok; Kang, Ju Hee; Kang, Jian; Karantzoulis, Stella; Kaushik, Sandeep S.; Kauwe, John; Kawashima, Shoji; Kaye, Edward; Kazemi, Samaneh; Ke, Han; Kelleher, Thomas; Kennedy, Richard; Keogh, Bart; Kerchner, Geoffrey; Kerr, Daniel; Keshava, Nirmal; Khalil, Andre; Khondker, Zakaria; Kiddle, Steven; Kihara, Takeshi; Killeen, Neil; Killiany, Ron; Kim, Jung-Hyun; Kim, Seongkyun; Kim, Dajung; Kim, Ana; Kim, Jong Hun; Kimberg, Daniel; King, Richard; Kirby, Justin; Kirsch, Wolff; Klein, Gregory; Klimas, Michael; Kline, Richard; Klopfenstein, Erin; Koen, Joshua; Koenig, Loren; Koikkalainen, Juha; Kokomoor, Anders; Kong, Xiangnan; Koppel, Jeremy; Korolev, Igor; Krahnke, Tillmann; Krams, Michael; Kuceyeski, Amy; Kuhl, Donald; Kumar, Vinod; Roy, P. Kumar; Kuo, Julie; Kyrtsos, Christina Rose; Labib, Victor; Labrish, Catherine; Lai, Song; Lakatos, Anita; Lalonde, François; Lam, Shing Chun Benny; Lam, On Ki; Lampron, Antoine; Landau, Susan; Lane, Barton; Langbaum, Jessica; Langford, Dianne; Lanius, Vivian; Lasch, Shirley; Latella, Marco; Hiuyan, Hiuyan; Leatherday, Christopher; Lee, Doheon; Lee, Grace; Lee, Sei; Lee, Jong an; Lemaitre, Herve; Lenfant, Pierre; Leonards, Ute; Leong, Leonards; Leoutsakos, Jeannie-Marie; Leung, Kelvin; Leung, Yuk Yee; Levey, Allan; Li, Ming; Li, Jie; Li, Xiaodong; Li, Lexin; Li, Yanming; Li, Quanzheng; Li, Rui; Li, Yi; Li, Junning; Li, Yue; Li, Jun; Li, Weidong; Li, Xiaobo; Liang, Peipeng; Liang, Kuchang; Liang, Kelvin; Liao, Weiqi; Liao, Shu; Liaquat, Saad; Liaw, Chyn; Liberman, Gilad; Lilley, Patrick; Lin, Frank; Lin, Xiaoman; Lin, Ai-Ling; Liu, Tianming; Liu, Yawu; Liu, Yanping; Liu, Linda; Liu, Wei; Liu, Collins; Liu, Manhua; Liu, Xiuwen; Liu, Tao; Liu, Ye; Liu, Xiaofeng; Liu, Yin; Liu, Dazhong; Liu, Sidong; Liu, Guodong; Llido, Jerome; Lo, Raymond; Lobach, Iryna; Lobanov, Victor; Lockhart, Andrew; Long, Ziyi; Long, Xiaojing; Long, Miaomiao; Looi, Jeffrey; Lu, Huanxiang; Lu, Yuefeng; Lu, Po-Haong; Lucena, Nathaniel; Luis, Jorge; Lukas, Carsten; Lukic, Ana; Luo, Xi; Luo, Xiongjian; Luo, Lei; Luo, Wanchun; Ma, Suk Ling; Ma, Shen-Ming; Mackin, Scott; Mada, Marius; Madabhushi, Anant; Madeira, Sara; Magland, Jeremy; Mahanta, Mohammad Shahin; Maikusa, Norihide; Maldjian, Joseph; Mandal, Indrajit; Mang, Mandal; Manjon, Jose; Mantri, Ninad; Manzour, Amir; Marcus, Daniel; Margolin, Richard; Marrett, Sean; Marshall, Gad; Martinez Gonzalez, Alberto; Martinez Torteya, Antonio; Martins, Renato; Mather, Mara; Mathis, Chester; Matoug, Sofia; Mattei, Peter; Matthews, Dawn; Mattis, Paul; McCarroll, Steven; McEvoy, Linda; McGeown, William; McGinnis, Scott; McGonigle, John; McIntosh, Anthony Randal; McIntyre, John; McLaren, McIntyre; McMillan, Corey; McQuail, Joseph; Meadowcroft, Mark; Meda, Shashwath; Melie-Garcia, Lester; Melrose, Rebecca; Mendelson, Alexander; Mendez, Mendelson; Menendez, Mendez; Meng, Meng; Meredith, Jere; Meyer, Carsten; Mez, Jesse; Mickael, Guedj; Mikula, Margit; Miller, Michael; Colleen, Colleen; Mintun, Mark; Mistridis, Panagiota; Mitchell, Mistridis; Mitsis, Effie; Mon, Mitsis; Moore, Dana; Morabito, Moore C.; Moradi Birgani, Parmida; Moratal, David; Morimoto, Bruce; Mormino, Elizabeth; Morris, Jill; Morris, Jeffrey; Mortamet, Bénédicte; Moscato, Pablo; Mourao-Miranda, Janaina; Mueller, Susanne; Mueller, Kathyrne; Mukherjee, Shubhabrata; Mukund, Nandita; Mulder, Emma; Mungas, Dan; Munir, Kamran; Murayama, Shigeo; N, Sairam; Nagata, Ken; Nair, Anil; Nasrabadi, Samira; Nativio, Raffaella; Nazeri, Arash; Nejad, Leila; Nekooei, Sirous; Nemeth, Imola; Nencka, Andrew; Nettiksimmons, Jasmine; Neu, Scott; Ng, Yen-Bee; Nguyen, Nghi; Nguyen, Hien; Nichols, Thomas; Nicodemus, Kristin; Niecko, Timothy; Nielsen, Casper; Niethammer, Marc; Nishio, Tomoyuki; Nordstrom, Matthew; Noshad, Sina; Notomi, Keiji; Novak, Nic; Nutakki, Gopi Chand; O'Charoen, Sirimon; Obisesan, Thomas; Oh, Joonmi; Okonkwo, Ozioma; Olde Rikkert, Marcel; Oliveira, João; Oliveira, Ailton; Oliver, Ruth; Olmos, Salvador; Oltra, Javier; Ong, Rowena; Ortner, Marion; Osadebey, Michael; Ostrowitzki, Susanne; Ovando Vazquez, Cesare Moises; Overholser, Rosanna; P, Anishiya; P K A, Chitra; Pa, Judy; Palanisamy, Preethi; Pan, Guodong; Pan, Zhifang; Pan, Sarah; Pande, Yogesh; Pardo, Jose; Pardoe, Heath; Park, Sujin; Park, Lovingly; Park, Moon Ho; Park, Hyunjin; Parker, Christopher; Patel, Yogen; Patil, Amol; Patil, Manasi; Pawlak, Mikolaj; Pierre, Pierre; Pell, Gaby; Pennec, Xavier; Pereira, Francisco; Perlbarg, Vincent; Perneczky, Robert; Peters, Frederic; Petitti, Diana; Petrella, Jeffrey; Petrou, Myria; Peyrat, Jean-Marc; Ngoc, Phuong Trinh Pham; Phillips, Justin; Phillips, Nicole; Pian, Wen-ting; Pierson, Ronald; Piovezan, Mauro; Pipitone, Jon; Pirraglia, Elizabeth; Planes, Xavi; Podhorski, Adam; Poirier, Judes; Pomara, Nunzio; Popov, Veljko; Poppenk, Jordan; Potkin, Steven; Potter, Guy; Poulin, Stephane; Prastawa, Marcel; Prince, Jerry; Pruessner, Jens; Qiu, Wendy; Qu, Annie; Qualls, Constance Dean; Quarg, Peter; Quinlan, Judith; Rabbia, Michael; Rajagovindan, Rajasimhan; Rajeesh, Rajeesh; Ramadubramani, Vanamamalai; Ramage, Amy; Ramirez, Alfredo; Randolph, Christopher; Rao, Hengyi; Rao, Anil; Reed, Bruce; Reid, Andrew; Reilhac, Anthonin; Reiner, Peggy; Reinsberger, Claus; Retico, Alessandra; Rhatigan, Lewis; Rhinn, Herve; Rhoades, Earl; Ribbens, Annemie; Richard, Edo; Richards, John; Richter, Mirco; Riddle, William; Ridgway, Gerard; Ringman, John; Rizk-Jackson, Angela; Rizzi, Massimo; Rodriguez, Laura; Rodriguez-Vieitez, Elena; Rogalski, Emily; Rojas Balderrama, Javier; Rokicki, Jaroslav; Romero, Klaus; Rorden, Chris; Jonathan, Jonathan; Rosen, Ori; Rostant, Ola; Rousseau, François; Rubright, Jonathan; Rucinski, Marek; Ruiz, Agustin; Rulseh, Aaron; Rusinek, Henry; Ryan, Laurie; Sabuncu, Mert; Saculva, Marie; Sahuquillo, Juan; Said, Yasmine; Saito, Naomi; Sakata, Muneyuki; Salama, Mahetab; Salazar, Diego; Saman, Sudad; Sanchez, Luciano; Sanders, Elizabeth; Sankar, Tejas; Santhamma, Sindhumol; Sarnel, Haldun; Sarwinda, Devvi; Sasaki, Toshiaki; Sasaya, Tenta; Sato, Hajime; Sattlecker, Martina; Savio, Alexandre; Saykin, Andrew; Scanlon, Blake; Scharre, Douglas; Schegerin, Marc; Schmand, Ben; Schmansky, Nick; Schmidt-Wilcke, Tobias; Schramm, Hauke; Schuerch, Markus; Schwartz, Pamela; Schwartz, Eben; Adam, Adam; Schwarz, John; Schweizer, Tom; Selnes, Per; Sembritzki, Klaus; Senjem, Matthew; Sfikas, Giorgos; Sghedoni, Roberto; Shah, Jamal Hussain; Shahbaba, Babak; Shams, Soheil; Shankle, William; Shattuck, David; Shaw, Leslie; Shen, Qi; Shen, Jie; Shen, Qian; Shera, David; Sherva, Richard; Shi, Yonghong; Shi, Feng; Shi, Yonggang; Shi, Jie; Shilaskar, Swati; Shinohara, Russell; Shokouhi, Sepideh; Shulman, Joshua; Sideris, Konstantinos; Siegel, Rene; Silveira, Margarida; Silverman, Daniel; Simak, Alex; Simmons, Andy; Simoes, Rita; Simon, Howard; Simon, Adam; Simpson, Ivor; Singh, Nikhil; Sinha, Neelam; Siuciak, Judy; Sjögren, Niclas; Skinner, Jeannine; Skudlarski, Skinner; Smith, Michael; Smith, Charles; Peter, Peter; Soares, Holly; Soldan, Anja; Soldea, Octavian; Solomon, Paul; Solomon, Alan; Som, Subhojit; Song, Zhuang; Song, Shide; Sosova, Iveta; Soydemir, Melih; Spampinato, Maria Vittoria; Speier, William; Sperling, Reisa; Spiegel, R.; Spies, Lothar; Springate, Beth; Spychalla, Anthony; Staff, Roger; Steenland, Nelson; Steffener, Jason; Stern, Yaakov; Stokman, Harro; Stolzenberg, Ethan; Stricker, Nikki; Stühler, Elisabeth; Su, Saisai; Suen, Summit; Sugishita, Morihiro; Suk, Heung-Il; Sukkar, Rafid; Sullivan, Sukkar; Sun, Mingzhu; Sun, Jia; Sun, Yu; Sun, Ying; Sundell, Karen; Sutphen, Courtney; Svetnik, Vladimir; Swan, Melanie; Symons, Sean; Szafranska, Katarzyna; Szigeti, Kinga; Szoeke, Cassandra; Sørensen, Lauge; T, Genish; Takeuchi, Tomoko; Tanaka, Shoji; Tanaka, Rie; Tanchi, Chaturaphat; Tancredi, Daniel; Tang, Qi; Tanzi, Rudolph; Tarnow, Eugen; Tartaglia, Maria Carmela; Tarver, Erika; Tassy, Dominique; Tauber, Dominique; Taylor-Reinwald, Lisa; Teipel, Stefan; Teng, Edmond; Termenon, Maite; Terriza, Felipe; Thambisetty, Madhav; Thames, April; Thatavarti, Raja Sekhar; Thiele, Frank; Thomas, Ronald; Thomas, Charlene; Thomas, Benjamin; Thompson, Paul; Thompson, Wesley; Thornton-Wells, Tricia; Thorvaldsson, Valgeir; Tokuda, Takahiko; Toledo, Juan B.; Toma, Ahmed; Tomita, Naoki; Toro, Roberto; Torrealdea, Patxi; Toschi, Nicola; Tosto, Giuseppe; Toussaint, Paule; Toyoshiba, Hiroyoshi; Tractenberg, Rochelle E.; Triggs, Tyler; Trittschuh, Emily; Trotta, Gabriele; Truong Huu, Tram; Truran, Diana; Tsalikakis, Dimitrios; Tsanas, Athanasios; Tsang, Candy; Tufail, Ahsan; Tung, Joyce; Turken, And; Turner, Raymond; Tyagi, Puneet; Ueda, Yoji; Uematsu, Daisuke; Ullrich, Lauren; Umar, Nisser; Ungar, Leo; Valenzuela, Olga; van de Nes, Joseph; van der Brug, Marcel; van der Lijn, Fedde; van Hecke, Wim; van Horn, John; van Leemput, Koen; van Train, Kenneth; Varkuti, Balint; Vasanawala, Minal; Veeraraghavan, Harini; Vellay, Stephane; Vemuri, Prashanthi; Verma, Manish; Vidoni, Eric; Louis, Louis; Vinyes, Georgina; Visser, Pieter Jelle; Vitek, Michael; Vogel, Simon; Voineskos, Aristotle; Vos, Stephanie; Vounou, Maria; Wade, Sara; Walsh, Alexander; Wang, Ze; Wang, Angela; Wang, Li; Wang, Yaping; Wang, Tiger; Wang, Li-San; Wang, Xu; Wang, Zheyu; Wang, Tianyao; Wang, Yongmei Michelle; Wang, Song; Wang, Lei; Wang, Lubin; Wang, Squall; Wang, Jingyan; Ward, Michael; Ward, Andrew; Watson, David; Wefel, Jeffrey; Weiner, Michael; Wenzel, Fabian; Wesnes, Keith; Shawn, Shawn; Westlye, Lars T.; Wheland, David; Whitcher, Brandon; White, Brooke; Whitlow, Christopher; Wilhelmsen, Kirk; Beth, Beth; Wilson, Lorraine; Wingo, Thomas; Wirth, Miranka; Wishart, Heather; Wiste, Heather; Wittemer, Elizabeth; Wolf, Henrike; Wolke, Ira; Wolz, Robin; Wong, Koon; Woo, Ellen; Woo, Jongwook; Woods, Lynn; Worth, Andrew; Wu, Xiaoying; Wu, Yanjun; Wu, Liang; Wu, Ellen; Wyman, Bradley; Xie, Sharon; Xu, Yonghong; Xu, Yi-Zheng; Xu, Shunbin; Xu, Jun; Xu, Steven; Yamada, Tomoko; Yamashita, Fumio; Yan, Yunyi; Yang, Zijiang; Yang, Hyun Duk; Yang, Edward; Yang, Chung-Yi; Yang, Wenlu; Yang, Hyuna; Yang, Eric; Yassa, Michael; Yavorsky, Christian; Ye, Byoung Seok; Yee, Laura; Yokoyama, Jennifer; Yokoyama, Takao; Stewart, Stewart; Younhyun, Jung; Yu, C. Q.; Yu, Peng; Yuan, Ying; Yuen, Bob; Yushkevich, Paul; Zaborszky, Laszlo; Zagorodnov, Vitali; Zahodne, Laura; Zarei, Mojtaba; Zeimpekis, Konstantinos; Zeitzer, Jamie; Zelinski, Elizabeth; Zeskind, Benjamin; Zhan, Xhu; Zhang, Tianhao; Zhang, Zhiguo; Zhang, Xiaoqun; Zhang, Ying; Zhang, Jing; Zhang, Daoqiang; Zhang, Lijun; Zhang, Kate; Zhang, Linda; Zhang, Zhe; Zhang, Ping; Zhao, Peng; Zhou, Luping; Zhou, Yongxia; Zhou, Bin; Zhu, Xuyan; Zhu, Hongtu; Zhu, Linling; Zhu, Zangen; Ziegler, Gabriel; Zilka, Samantha; Zisserman, Andrew; Zito, Giancarlo; Zu, Zito; Zulfigar, Annam

    2012-01-01

    Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures

  1. Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume.

    NARCIS (Netherlands)

    Carmichael, O.; Xie, J.; Fletcher, E.; Singh, B.; DeCarli, C.; Olde Rikkert, M.; et al.,

    2012-01-01

    Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures

  2. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment.

    Science.gov (United States)

    Papma, Janne M; Smits, Marion; de Groot, Marius; Mattace Raso, Francesco U; van der Lugt, Aad; Vrooman, Henri A; Niessen, Wiro J; Koudstaal, Peter J; van Swieten, John C; van der Veen, Frederik M; Prins, Niels D

    2017-09-01

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI.

  3. Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.

    LENUS (Irish Health Repository)

    Frodl, T

    2012-01-01

    Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and\\/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.

  4. Hippocampal Gαq/11 but not Gαo-coupled receptors are altered in aging

    Science.gov (United States)

    McQuail, Joseph A.; Davis, Kathleen N.; Miller, Frances; Hampson, Robert E.; Deadwyler, Samuel A.; Howlett, Allyn C.; Nicolle, Michelle M.

    2013-01-01

    Normal aging may limit the signaling efficacy of certain GPCRs by disturbing the function of specific Gα-subunits and leading to deficient modulation of intracellular functions that subserve synaptic plasticity, learning and memory. Evidence suggests that Gαq/11 is more sensitive to the effects of aging relative to other Gα-subunits, including Gαo. To test this hypothesis, the functionality of Gαq/11 and Gαo were compared in the hippocampus of young (6 months) and aged (24 months) F344×BNF1 hybrid rats assessed for spatial learning ability. Basal GTPγS-binding to Gαq/11 was significantly elevated in aged rats relative to young and but not reliably associated with spatial learning. mAChR stimulation of Gαq/11 with oxotremorine-M produced equivocal GTPγS-binding between age groups although values tended to be lower in the aged hippocampus and were inversely related to basal activity. Downstream Gαq/11 function was measured in hippocampal subregion CA1 by determining changes in [Ca2+]i after mAChR and mGluR (DHPG) stimulation. mAChR-stimulated peak change in [Ca2+]i was lower in aged CA1 relative to young while mGluR-mediated integrated [Ca2+]i responses tended to be larger in aged. GPCR modulation of [Ca2+]i was observed to depend on intracellular stores to a greater degree in aged than young. In contrast, measures of Gαo-mediated GTPγS-binding were stable across age, including basal, mAChR-, GABABR (baclofen)-stimulated levels. Overall, the data indicate that aging selectively modulates the activity of Gαq/11 within the hippocampus leading to deficient modulation of [Ca2+]i following stimulation of mAChRs but these changes are not related to spatial learning. PMID:23347951

  5. Magnetic Resonance Imaging-Based Measurement of Hippocampal Volume in Posttraumatic Stress Disorder Related to Childhood Physical and Sexual Abuse—A Preliminary Report

    Science.gov (United States)

    Bremner, J. Douglas; Randall, Penny; Vermetten, Eric; Staib, Lawrence; Bronen, Richard A.; Mazure, Carolyn; Capelli, Sandi; McCarthy, Gregory; Innis, Robert B.; Charney, Dennis S.

    2011-01-01

    We have previously reported smaller hippocampal volume and deficits in short-term memory in patients with combat-related posttraumatic stress disorder (PTSD) relative to comparison subjects. The purpose of this study was to compare hippocampal volume in adult survivors of childhood abuse to matched controls. Magnetic resonance imaging was used to measure volume of the hippocampus in adult survivors of childhood abuse (n = 17) and healthy subjects (n = 17) matched on a case-by-case basis for age, sex, race, handedness, years of education, body size, and years of alcohol abuse. All patients met criteria for PTSD secondary to childhood abuse. PTSD patients had a 12% smaller left hippocampal volume relative to the matched controls (p < .05), without smaller volumes of comparison regions (amygdala, caudate, and temporal lobe). The findings were significant after controlling for alcohol, age, and education, with multiple linear regression. These findings suggest that a decrease in left hippocampal volume is associated with abuse-related PTSD. PMID:8988792

  6. Altered Chloride Homeostasis Decreases the Action Potential Threshold and Increases Hyperexcitability in Hippocampal Neurons

    DEFF Research Database (Denmark)

    Sørensen, Andreas T; Ledri, Marco; Melis, Miriam

    2017-01-01

    neurons, and promote AP generation. It is generally recognized that altered chloride homeostasis per se has no effect on the AP threshold. Here, we demonstrate that chloride overload of mouse principal CA3 pyramidal neurons not only makes these cells more excitable through GABAA receptor activation...... homeostasis. This finding further broadens the spectrum of neuronal plasticity regulated by ionic compositions across the cellular membrane....

  7. Oxygen glucose deprivation in rat hippocampal slice cultures results in alterations in carnitine homeostasis and mitochondrial dysfunction.

    Directory of Open Access Journals (Sweden)

    Thomas F Rau

    Full Text Available Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD decreased the levels of free carnitines (FC and increased the acylcarnitine (AC: FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC∶FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD.

  8. Maternal cocaine administration in mice alters DNA methylation and gene expression in hippocampal neurons of neonatal and prepubertal offspring.

    Directory of Open Access Journals (Sweden)

    Svetlana I Novikova

    2008-04-01

    Full Text Available Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8-19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3 or 30 (P30 days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI(2 microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression analysis, were evaluated in hippocampal pyramidal neurons excised by laser capture microdissection. Following maternal cocaine exposure, global DNA methylation was significantly decreased at P3 and increased at P30. Among the 492 CGIs whose methylation was significantly altered by cocaine at P3, 34% were hypermethylated while 66% were hypomethylated. Several of these CGIs contained promoter regions for genes implicated in crucial cellular functions. Endogenous expression of selected genes linked to the abnormally methylated CGIs was correspondingly decreased or increased by as much as 4-19-fold. By P30, some of the cocaine-associated effects at P3 endured, reversed to opposite directions, or disappeared. Further, additional sets of abnormally methylated targets emerged at P30 that were not observed at P3. Taken together, these observations indicate that maternal cocaine exposure during the second and third trimesters of gestation could produce potentially profound structural and functional modifications in the epigenomic programs of neonatal and prepubertal mice.

  9. Early mood behavioral changes following exposure to monotonous environment during isolation stress is associated with altered hippocampal synaptic plasticity in male rats.

    Science.gov (United States)

    Das, Saroj Kumar; Baitharu, Iswar; Barhwal, Kalpana; Hota, Sunil Kumar; Singh, Shashi Bala

    2016-01-26

    Social isolation stress and its effect on mood have been well reported, but the effect of monotony (a state of repetition of events for a considerable period of time without variation) on mood and hippocampal synaptic plasticity needs to be addressed. Present study was conducted on male Sprague-Dawley rats. Singly housed (SH) rats were subjected to monotony stress by physical, visual and pheromonal separation in specially designed animal segregation chamber. Fluoxetine (a selective serotonin reuptake inhibitor) was administered orally. Behavioral assessment showed anxiety and depression like traits in SH group. Monotony stress exposure to SH group resulted in increased pyknosis, decreased apical dendritic arborization and increased asymmetric (excitatory) synapses with the corresponding decrease in the symmetric (inhibitory) synapses in the hippocampal CA3 region. Monotonous environment during isolation stress also decreased the serotonin level and reduced the expression of synaptophysin and pCREB in the hippocampus. Fluoxetine administration to singly housed rats resulted in amelioration of altered mood along with improvement in serotonin and decrease in excitatory synaptic density but no change in altered inhibitory synaptic density in the hippocampus. These findings suggest that monotony during isolation contributes to early impairment in mood state by altering hippocampal synaptic density and neuronal morphology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome.

    Science.gov (United States)

    Dinel, Anne-Laure; André, Caroline; Aubert, Agnès; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie

    2011-01-01

    Converging clinical data suggest that peripheral inflammation is likely involved in the pathogenesis of the neuropsychiatric symptoms associated with metabolic syndrome (MetS). However, the question arises as to whether the increased prevalence of behavioral alterations in MetS is also associated with central inflammation, i.e. cytokine activation, in brain areas particularly involved in controlling behavior. To answer this question, we measured in a mouse model of MetS, namely the diabetic and obese db/db mice, and in their healthy db/+ littermates emotional behaviors and memory performances, as well as plasma levels and brain expression (hippocampus; hypothalamus) of inflammatory cytokines. Our results shows that db/db mice displayed increased anxiety-like behaviors in the open-field and the elevated plus-maze (i.e. reduced percent of time spent in anxiogenic areas of each device), but not depressive-like behaviors as assessed by immobility time in the forced swim and tail suspension tests. Moreover, db/db mice displayed impaired spatial recognition memory (hippocampus-dependent task), but unaltered object recognition memory (hippocampus-independent task). In agreement with the well-established role of the hippocampus in anxiety-like behavior and spatial memory, behavioral alterations of db/db mice were associated with increased inflammatory cytokines (interleukin-1β, tumor necrosis factor-α and interleukin-6) and reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus but not the hypothalamus. These results strongly point to interactions between cytokines and central processes involving the hippocampus as important contributing factor to the behavioral alterations of db/db mice. These findings may prove valuable for introducing novel approaches to treat neuropsychiatric complications associated with MetS.

  11. Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Dinel

    Full Text Available Converging clinical data suggest that peripheral inflammation is likely involved in the pathogenesis of the neuropsychiatric symptoms associated with metabolic syndrome (MetS. However, the question arises as to whether the increased prevalence of behavioral alterations in MetS is also associated with central inflammation, i.e. cytokine activation, in brain areas particularly involved in controlling behavior. To answer this question, we measured in a mouse model of MetS, namely the diabetic and obese db/db mice, and in their healthy db/+ littermates emotional behaviors and memory performances, as well as plasma levels and brain expression (hippocampus; hypothalamus of inflammatory cytokines. Our results shows that db/db mice displayed increased anxiety-like behaviors in the open-field and the elevated plus-maze (i.e. reduced percent of time spent in anxiogenic areas of each device, but not depressive-like behaviors as assessed by immobility time in the forced swim and tail suspension tests. Moreover, db/db mice displayed impaired spatial recognition memory (hippocampus-dependent task, but unaltered object recognition memory (hippocampus-independent task. In agreement with the well-established role of the hippocampus in anxiety-like behavior and spatial memory, behavioral alterations of db/db mice were associated with increased inflammatory cytokines (interleukin-1β, tumor necrosis factor-α and interleukin-6 and reduced expression of brain-derived neurotrophic factor (BDNF in the hippocampus but not the hypothalamus. These results strongly point to interactions between cytokines and central processes involving the hippocampus as important contributing factor to the behavioral alterations of db/db mice. These findings may prove valuable for introducing novel approaches to treat neuropsychiatric complications associated with MetS.

  12. Hippocampal volume change measurement: Quantitative assessment of the reproducibility of expert manual outlining and the automated methods FreeSurfer and FIRST

    NARCIS (Netherlands)

    Mulder, E.R.; de Jong, R.A.; Knol, D.L.; van Schijndel, R.A.; Cover, K.S.; Visser, P.J.; Barkhof, F.; Vrenken, H.

    2014-01-01

    Background: To measure hippocampal volume change in Alzheimer's disease (AD) or mild cognitive impairment (MCI), expert manual delineation is often used because of its supposed accuracy. It has been suggested that expert outlining yields poorer reproducibility as compared to automated methods, but

  13. Altered hippocampal arteriole structure and function in a rat model of preeclampsia: Potential role in impaired seizure-induced hyperemia.

    Science.gov (United States)

    Johnson, Abbie C; Cipolla, Marilyn J

    2017-08-01

    We investigated the effect of experimental preeclampsia on hyperemia during seizure in the hippocampus and vascular function and structure of hippocampal arterioles using Sprague Dawley rats (n = 14/group) that were nonpregnant, pregnant (d20), or had experimental preeclampsia (induced by a high cholesterol diet d7-20). Hyperemia was measured via hydrogen clearance basally and during pentylenetetrazol-induced seizure (40-130 mg/kg i.v.). Reactivity of isolated and pressurized hippocampal arterioles to KCl, nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester and the nitric oxide donor sodium nitroprusside were investigated. Capillary density was quantified via immunohistochemistry. Cerebral blood flow increased during seizure vs. baseline in pregnant (118 ± 14 vs. 87 ± 9 mL/100 g/min; p  0.05), suggesting impaired seizure-induced hyperemia in preeclampsia. Hippocampal arterioles from preeclamptic rats had less basal tone, and dilated less to 15 mM KCl (9 ± 8%) vs. pregnant (61 ± 27%) and nonpregnant rats (20 ± 11%). L-NAME had no effect on hippocampal arterioles in any group, but dilation to sodium nitroprusside was similar. Structurally, hippocampal arterioles from preeclamptic rats underwent inward hypotrophic remodeling and capillary rarefaction. Impaired seizure-induced hyperemia, vascular dysfunction, and limited vasodilatory reserve of hippocampal arterioles could potentiate hippocampal injury in preeclampsia especially during eclampsia.

  14. Changes in hippocampal volume and neuron number co-occur with memory decline in old homing pigeons (Columba livia).

    Science.gov (United States)

    Coppola, Vincent J; Kanyok, Nate; Schreiber, Austin J; Flaim, Mary E; Bingman, Verner P

    2016-05-01

    The mammalian hippocampus is particularly susceptible to age-related structural changes, which have been used to explain, in part, age-related memory decline. These changes are generally characterized by atrophy (e.g., a decrease in volume and number of synaptic contacts). Recent studies have reported age-related spatial memory deficits in older pigeons similar to those seen in older mammals. However, to date, little is known about any co-occurring changes in the aging avian hippocampal formation (HF). In the current study, it was found that the HF of older pigeons was actually larger and contained more neurons than the HF of younger pigeons, a finding that suggests that the pattern of structural changes during aging in the avian HF is different from that seen in the mammalian hippocampus. A working hypothesis for relating the observed structural changes with spatial-cognitive decline is offered. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Addictive nicotine alters local circuit inhibition during the induction of in vivo hippocampal synaptic potentiation.

    Science.gov (United States)

    Zhang, Tao A; Tang, Jianrong; Pidoplichko, Volodymyr I; Dani, John A

    2010-05-05

    The drug addiction process shares many commonalities with normal learning and memory. Addictive drugs subvert normal synaptic plasticity mechanisms, and the consequent synaptic changes underlie long-lasting modifications in behavior that accrue during the progression from drug use to addiction. Supporting this hypothesis, it was recently shown that nicotine administered to freely moving mice induces long-term synaptic potentiation of the perforant path connection to granule cells of the dentate gyrus. The perforant path carries place and spatial information that links the environment to drug taking. An example of that association is the nicotine-induced synaptic potentiation of the perforant path that was found to underlie nicotine-conditioned place preference. The present study examines the influence of nicotine over local GABAergic inhibition within the dentate gyrus during the drug-induced synaptic potentiation. In vivo recordings from freely moving mice suggested that both feedforward and feedback inhibition onto granules cells were diminished by nicotine during the induction of synaptic potentiation. In vitro brain slice studies indicated that nicotine altered local circuit inhibition within the dentate gyrus leading to disinhibition of granule cells. These changes in local inhibition contributed to nicotine-induced in vivo synaptic potentiation, thus, likely contributed to drug-associated memories. Through this learning process, environmental features become cues that motivate conditioned drug-seeking and drug-taking behaviors.

  16. Progressive Decline in Hippocampal CA1 Volume in Individuals at Ultra-High-Risk for Psychosis Who Do Not Remit: Findings from the Longitudinal Youth at Risk Study.

    Science.gov (United States)

    Ho, New Fei; Holt, Daphne J; Cheung, Mike; Iglesias, Juan Eugenio; Goh, Alex; Wang, Mingyuan; Lim, Joseph Kw; de Souza, Joshua; Poh, Joann S; See, Yuen Mei; Adcock, Alison R; Wood, Stephen J; Chee, Michael Wl; Lee, Jimmy; Zhou, Juan

    2017-05-01

    Most individuals identified as ultra-high-risk (UHR) for psychosis do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia. Here we aimed to determine whether patterns of volume change of CA1 are different in UHR individuals who do or do not achieve symptomatic remission. Structural MRI scans were acquired at baseline and at 1-2 follow-up time points (at 12-month intervals) from 147 UHR and healthy control subjects. An automated method (based on an ex vivo atlas of ultra-high-resolution hippocampal tissue) was used to delineate the hippocampal subfields. Over time, a greater decline in bilateral CA1 subfield volumes was found in the subgroup of UHR subjects whose subthreshold symptoms persisted (n=40) and also those who developed clinical psychosis (n=12), compared with UHR subjects who remitted (n=41) and healthy controls (n=54). No baseline differences in volumes of the overall hippocampus or its subfields were found among the groups. Moreover, the rate of volume decline of CA1, but not of other hippocampal subfields, in the non-remitters was associated with increasing symptom severity over time. Thus, these findings indicate that there is deterioration of CA1 volume in persistently symptomatic UHR individuals in proportion to symptomatic progression.

  17. Gestational treatment with methylazoxymethanol (MAM) that disrupts hippocampal-dependent memory does not alter behavioural response to cocaine.

    Science.gov (United States)

    Featherstone, Robert E; Burton, Christie L; Coppa-Hopman, Romina; Rizos, Zoë; Sinyard, Judy; Kapur, Shitij; Fletcher, Paul J

    2009-10-01

    Schizophrenia is associated with increased rates of substance abuse that are thought to be the result of changes in cortical and mesolimbic dopamine activity. Previous work has shown that gestational methylazoxymethanol acetate (MAM) treatment induces increased mesolimbic dopamine activity when given around the time of embryonic day 17 (ED17), suggesting that MAM treatment may model some aspects of schizophrenia. Given that increased dopaminergic activity facilitates aspects of drug self-administration and reinstatement of drug seeking, the current experiments sought to assess cocaine self-administration in MAM treated animals. Experiment 1 examined the acquisition of cocaine self-administration in ED17 MAM and saline treated rats using a sub-threshold dose of cocaine. In experiment 2 ED17 MAM and saline treated animals were trained to self-administer cocaine and were then assessed under varying doses of cocaine (dose-response), followed by extinction and drug-induced reinstatement of responding. A subset of these animals was trained on a win-shift radial maze task, designed to detect impairments in hippocampal-dependent memory. In experiment 3, MAM and saline treated animals were assessed on a progressive ratio schedule of cocaine delivery. Finally, in experiment 4 MAM and saline treated animals were assessed on cocaine-induced locomotor activity across a range of doses of cocaine. MAM treatment disrupted performance of the win-shift task but did not alter cocaine self-administration or cocaine-induced locomotion. Implications of these results for the MAM model of schizophrenia are discussed.

  18. Chronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis.

    Science.gov (United States)

    de Andrade, J S; Céspedes, I C; Abrão, R O; Dos Santos, T B; Diniz, L; Britto, L R G; Spadari-Bratfisch, R C; Ortolani, D; Melo-Thomas, L; da Silva, R C B; Viana, M B

    2013-08-01

    Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. In unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. In stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. In stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. 17β-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes.

    Science.gov (United States)

    Mitrović, Nataša; Zarić, Marina; Drakulić, Dunja; Martinović, Jelena; Sévigny, Jean; Stanojlović, Miloš; Nedeljković, Nadežda; Grković, Ivana

    2017-03-01

    17β-Estradiol (E2) rapidly, by binding to membrane estrogen receptors, activates cell signaling cascades which induce formation of new dendritic spines in the hippocampus of males as in females, but the interaction with other metabolic processes, such as extracellular adenine nucleotides metabolism, are currently unknown. Extracellular adenine nucleotides play significant roles, controlling excitatory glutamatergic synapses and development of neural circuits and synaptic plasticity. Their precise regulation in the synaptic cleft is tightly controlled by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, we sought to clarify whether a single systemic injection of E2 in male rats is accompanied by changes in the expression of the pre- and postsynaptic proteins and downstream kinases linked to E2-induced synaptic rearrangement as well as alterations in NTPDase/eN pathway in the hippocampal synaptosomes. Obtained data showed activation of mammalian target of rapamycin and upregulation of key synaptic proteins necessary for spine formation, 24 h after systemic E2 administration. In E2-mediated conditions, we found downregulation of NTPDase1 and NTPDase2 and attenuation of adenine nucleotide hydrolysis by NTPDase/eN enzyme chain, without changes in NTPDase3 properties and augmentation of synaptic tissue-nonspecific alkaline phosphatase (TNAP) activity. Despite reduced NTPDase activities, increased TNAP activity probably prevents toxic accumulation of ATP in the extracellular milieu and also hydrolyzes accumulated ADP due to unchanged NTPDase3 activity. Thus, our initial evaluation supports idea of specific roles of different ectonucleotidases and their coordinated actions in E2-mediated spine remodeling and maintenance.

  20. Effects of melatonin on prenatal dexamethasone-induced epigenetic alterations in hippocampal morphology and reelin and glutamic acid decarboxylase 67 levels.

    Science.gov (United States)

    Lui, Chun-Chung; Hsu, Mei-Hsin; Kuo, Ho-Chang; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Tain, You-Lin; Chang, Kow-Aung; Huang, Li-Tung

    2015-01-01

    Prenatal glucocorticoid exposure causes brain damage in adult offspring; however, the underlying mechanisms remain unclear. Melatonin has been shown to have beneficial effects in compromised pregnancies. Pregnant Sprague-Dawley rats were administered vehicle (VEH) or dexamethasone between gestation days 14 and 21. The programming effects of prenatal dexamethasone exposure on the brain were assessed at postnatal days (PND) 7, 42, and ∼120. Melatonin was administered from PND21 to the rats exposed to dexamethasone, and the outcome was assessed at ∼PND120. In total, there were four groups: VEH, vehicle plus melatonin (VEHM), prenatal dexamethasone-exposure (DEX), and prenatal dexamethasone exposure plus melatonin (DEXM). Spatial memory, gross hippocampal morphology, and hippocampal biochemistry were examined. Spatial memory assessed by the Morris water maze showed no significant differences among the four groups. Brain magnetic resonance imaging showed that all rats with prenatal dexamethasone exposure (DEX + DEXM) exhibited increased T2-weighted signals in the hippocampus. There were no significant differences in the levels of mRNA expression of hippocampal reln, which encodes reelin, and GAD1, which encodes glutamic acid decarboxylase 67, at PND7. At both PND42 and ∼PND120, reln and GAD1 mRNA expression levels were decreased. At ∼PND120, melatonin restored the reduced levels of hippocampal reln and GAD1 mRNA expression in the DEXM group. In addition, melatonin restored the reln mRNA expression levels by (1) reducing DNA methyltransferase 1 (DNMT1) mRNA expression and (2) reducing the binding of DNMT1 and the methyl-CpG binding protein 2 (MeCP2) to the reln promoter. The present study showed that prenatal dexamethasone exposure induced gross alterations in hippocampal morphology and reduced the levels of hippocampal mRNA expression of reln and GAD1. Spatial memory was unimpaired. Thus, melatonin had a beneficial effect in restoring hippocampal reln m

  1. The opposite effects of nandrolone decanoate and exercise on anxiety levels in rats may involve alterations in hippocampal parvalbumin-positive interneurons.

    Directory of Open Access Journals (Sweden)

    Dragica Selakovic

    Full Text Available The aim of this study was to evaluate the behavioral effects of chronic (six weeks nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose administration (in order to mimic heavy human abuse, and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break, applied alone and simultaneously with ND, in male rats (n = 40. Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone and in elevated plus maze (EPM test (decrease in frequency and cumulative duration in open arms, and total exploratory activity, that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region, followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters, and in evoked beam-walking test (increase in time to cross the beam, compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols.

  2. PCB 136 Atropselectively Alters Morphometric and Functional Parameters of Neuronal Connectivity in Cultured Rat Hippocampal Neurons via Ryanodine Receptor-Dependent Mechanisms

    Science.gov (United States)

    Yang, Dongren; Kania-Korwel, Izabela; Ghogha, Atefeh; Chen, Hao; Stamou, Marianna; Bose, Diptiman D.; Pessah, Isaac N.; Lehmler, Hans-Joachim; Lein, Pamela J.

    2014-01-01

    We recently demonstrated that polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyRs), and this activity promotes Ca2+-dependent dendritic growth in cultured neurons. Many ortho-substituted congeners display axial chirality, and we previously reported that the chiral congener PCB 136 (2,2′,3,3′,6,6′-hexachlorobiphenyl) atropselectively sensitizes RyRs. Here, we test the hypothesis that PCB 136 atropisomers differentially alter dendritic growth and other parameters of neuronal connectivity influenced by RyR activity. (−)-PCB 136, which potently sensitizes RyRs, enhances dendritic growth in primary cultures of rat hippocampal neurons, whereas (+)-PCB 136, which lacks RyR activity, has no effect on dendritic growth. The dendrite-promoting activity of (−)-PCB 136 is observed at concentrations ranging from 0.1 to 100nM and is blocked by pharmacologic RyR antagonism. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB 136 atropisomers in hippocampal cultures indicates that atropselective effects on dendritic growth are not due to differential partitioning of atropisomers into cultured cells. Imaging of hippocampal neurons loaded with Ca2+-sensitive dye demonstrates that (−)-PCB 136 but not (+)-PCB 136 increases the frequency of spontaneous Ca2+ oscillations. Similarly, (−)-PCB 136 but not (+)-PCB 136 increases the activity of hippocampal neurons plated on microelectrode arrays. These data support the hypothesis that atropselective effects on RyR activity translate into atropselective effects of PCB 136 atropisomers on neuronal connectivity, and suggest that the variable atropisomeric enrichment of chiral PCBs observed in the human population may be a significant determinant of individual susceptibility for adverse neurodevelopmental outcomes following PCB exposure. PMID:24385416

  3. Altered Gray Matter Volume and White Matter Integrity in College Students with Mobile Phone Dependence.

    Science.gov (United States)

    Wang, Yongming; Zou, Zhiling; Song, Hongwen; Xu, Xiaodan; Wang, Huijun; d'Oleire Uquillas, Federico; Huang, Xiting

    2016-01-01

    Mobile phone dependence (MPD) is a behavioral addiction that has become an increasing public mental health issue. While previous research has explored some of the factors that may predict MPD, the underlying neural mechanisms of MPD have not been investigated yet. The current study aimed to explore the microstructural variations associated with MPD as measured with functional Magnetic Resonance Imaging (fMRI). Gray matter volume (GMV) and white matter (WM) integrity [four indices: fractional anisotropy (FA); mean diffusivity (MD); axial diffusivity (AD); and radial diffusivity (RD)] were calculated via voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis, respectively. Sixty-eight college students (42 female) were enrolled and separated into two groups [MPD group, N = 34; control group (CG), N = 34] based on Mobile Phone Addiction Index (MPAI) scale score. Trait impulsivity was also measured using the Barratt Impulsiveness Scale (BIS-11). In light of underlying trait impulsivity, results revealed decreased GMV in the MPD group relative to controls in regions such as the right superior frontal gyrus (sFG), right inferior frontal gyrus (iFG), and bilateral thalamus (Thal). In the MPD group, GMV in the above mentioned regions was negatively correlated with scores on the MPAI. Results also showed significantly less FA and AD measures of WM integrity in the MPD group relative to controls in bilateral hippocampal cingulum bundle fibers (CgH). Additionally, in the MPD group, FA of the CgH was also negatively correlated with scores on the MPAI. These findings provide the first morphological evidence of altered brain structure with mobile phone overuse, and may help to better understand the neural mechanisms of MPD in relation to other behavioral and substance addiction disorders.

  4. Altered gray matter volume and white matter integrity in college students with mobile phone dependence

    Directory of Open Access Journals (Sweden)

    Yongming eWang

    2016-05-01

    Full Text Available Mobile phone dependence (MPD is a behavioral addiction that has become an increasing public mental health issue. While previous research has explored some of the factors that may predict MPD, the underlying neural mechanisms of MPD have not been investigated yet. The current study aimed to explore the microstructural variations associated with MPD as measured with functional Magnetic Resonance Imaging (fMRI. Gray matter volume (GMV and white matter (WM integrity (four indexes: fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, AD; and radial diffusivity, RD were calculated via voxel-based morphometry (VBM and tract-based spatial statistics (TBSS analysis, respectively. Sixty-eight college students (42 female were enrolled and separated into two groups (MPD group, N=34; control group, N=34 based on Mobile Phone Addiction Index (MPAI scale score. Trait impulsivity was also measured using the Barrett Impulsivity Scale (BIS-11. In light of underlying trait impulsivity, results revealed decreased GMV in the MPD group relative to controls in regions such as the right superior frontal gyrus (sFG, right inferior frontal gyrus (iFG, and bilateral thalamus (Thal. In the MPD group, GMV in the above mentioned regions was negatively correlated with scores on the MPAI. Results also showed significantly less FA and AD measures of white matter integrity in the MPD group relative to controls in bilateral hippocampal cingulum bundle fibers (CgH. Additionally, in the MPD group, FA of the CgH was also negatively correlated with scores on the MPAI. These findings provide the first morphological evidence of altered brain structure with phone-overuse, and may help to better understand the neural mechanisms of MPD in relation with other behavioral and substance addiction disorders.

  5. Knockout of Amyloid β Protein Precursor (APP) Expression Alters Synaptogenesis, Neurite Branching and Axonal Morphology of Hippocampal Neurons.

    Science.gov (United States)

    Southam, Katherine A; Stennard, Fiona; Pavez, Cassandra; Small, David H

    2018-03-23

    The function of the β-A4 amyloid protein precursor (APP) of Alzheimer's disease (AD) remains unclear. APP has a number of putative roles in neuronal differentiation, survival, synaptogenesis and cell adhesion. In this study, we examined the development of axons, dendrites and synapses in cultures of hippocampus neutrons derived from APP knockout (KO) mice. We report that loss of APP function reduces the branching of cultured hippocampal neurons, resulting in reduced synapse formation. Using a compartmentalised culture approach, we found reduced axonal outgrowth in cultured hippocampal neurons and we also identified abnormal growth characteristics of isolated hippocampal neuron axons. Although APP has previously been suggested to play an important role in promoting cell adhesion, we surprisingly found that APPKO hippocampal neurons adhered more strongly to a poly-L-lysine substrate and their neurites displayed an increased density of focal adhesion puncta. The findings suggest that the function of APP has an important role in both dendritic and axonal growth and that endogenous APP may regulate substrate adhesion of hippocampal neurons. The results may explain neuronal and synaptic morphological abnormalities in APPKO mice and the presence of abnormal APP expression in dystrophic neurites around amyloid deposits in AD.

  6. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    Energy Technology Data Exchange (ETDEWEB)

    Papma, Janne M.; Koudstaal, Peter J.; Swieten, John C. van [Erasmus MC - University Medical Center Rotterdam, Department of Neurology, Rotterdam (Netherlands); Smits, Marion; Lugt, Aad van der [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Groot, Marius de; Vrooman, Henri A. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Erasmus MC - University Medical Center Rotterdam, Department of Medical Informatics, Rotterdam (Netherlands); Mattace Raso, Francesco U. [Erasmus MC - University Medical Center Rotterdam, Department of Geriatrics, Rotterdam (Netherlands); Niessen, Wiro J. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Erasmus MC - University Medical Center Rotterdam, Department of Medical Informatics, Rotterdam (Netherlands); Delft University of Technology, Faculty of Applied Sciences, Delft (Netherlands); Veen, Frederik M. van der [Erasmus University Rotterdam, Institute of Psychology, Rotterdam (Netherlands); Prins, Niels D. [VU University Medical Center, Alzheimer Center, Department of Neurology, Amsterdam (Netherlands)

    2017-09-15

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. (orig.)

  7. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    International Nuclear Information System (INIS)

    Papma, Janne M.; Koudstaal, Peter J.; Swieten, John C. van; Smits, Marion; Lugt, Aad van der; Groot, Marius de; Vrooman, Henri A.; Mattace Raso, Francesco U.; Niessen, Wiro J.; Veen, Frederik M. van der; Prins, Niels D.

    2017-01-01

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. (orig.)

  8. Lateralization of temporal lobe epilepsy using a novel uncertainty analysis of MR diffusion in hippocampus, cingulum, and fornix, and hippocampal volume and FLAIR intensity.

    Science.gov (United States)

    Nazem-Zadeh, Mohammad-Reza; Schwalb, Jason M; Elisevich, Kost V; Bagher-Ebadian, Hassan; Hamidian, Hajar; Akhondi-Asl, Ali-Reza; Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid

    2014-07-15

    To analyze the utility of a quantitative uncertainty analysis approach for evaluation and comparison of various MRI findings for the lateralization of epileptogenicity in mesial temporal lobe epilepsy (mTLE), including novel diffusion-based analyses. We estimated the hemispheric variation uncertainty (HVU) of hippocampal T1 volumetry and FLAIR (Fluid Attenuated Inversion Recovery) intensity. Using diffusion tensor images of 23 nonepileptic subjects, we estimated the HVU levels of mean diffusivity (MD) in the hippocampus, and fractional anisotropy (FA) in the posteroinferior cingulum and crus of fornix. Imaging from a retrospective cohort of 20 TLE patients who had undergone surgical resection with Engel class I outcomes was analyzed to determine whether asymmetry of preoperative volumetrics, FLAIR intensities, and MD values in hippocampi, as well as FA values in posteroinferior cingula and fornix crura correctly predicted laterality of seizure onset. Ten of the cohort had pathologically proven mesial temporal sclerosis (MTS). Seven of these patients had undergone extraoperative electrocorticography (ECoG) for lateralization or to rule out extra-temporal foci. HVU was estimated to be 3.1×10(-5) for hippocampal MD, 0.027 for FA in posteroinferior cingulum, 0.018 for FA in crus of fornix, 0.069 for hippocampal normalized volume, and 0.099 for hippocampal normalized FLAIR intensity. Using HVU analysis, a higher hippocampal MD value, lower FA within the posteroinferior cingulum and crus of fornix, shrinkage in hippocampal volume, and higher hippocampal FLAIR intensity were observed beyond uncertainty on the side ipsilateral to seizure onset for 10, 10, 9, 9, and 10 out of 10 pathology-proven MTS patients, respectively. Considering all 20 TLE patients, these numbers were 18, 15, 14, 13, and 16, respectively. However, consolidating the lateralization results of HVU analysis on these quantities by majority voting has detected the epileptogenic side for 19 out of 20 cases

  9. Sex differences in resilience to childhood maltreatment: effects of trauma history on hippocampal volume, general cognition and subclinical psychosis in healthy adults.

    Science.gov (United States)

    Samplin, Erin; Ikuta, Toshikazu; Malhotra, Anil K; Szeszko, Philip R; Derosse, Pamela

    2013-09-01

    Recent data suggests that a history of childhood maltreatment is associated with reductions in hippocampal volume in healthy adults. Because this association is also evident in adults with psychiatric illness, it has been suggested that reductions in hippocampal volume associated with childhood maltreatment may be a risk factor for psychiatric illness. Such an interpretation suggests that healthy adults with a history of childhood maltreatment are more resilient to the effects of maltreatment. Current models of resilience suggest, however, that resiliency should be measured across multiple domains of functioning. The present study sought to investigate childhood maltreatment in relationship to hippocampal volumes in healthy adults and to address the question of whether the putative resiliency extends to other domains of functioning. Sixty-seven healthy Caucasian adults were assessed for a history of childhood emotional abuse, emotional neglect and physical abuse and received high resolution structural MR imaging scans. Participants with and without histories of abuse or neglect were compared on measures of total hippocampal volume, general cognitive ability and subclinical psychopathology. Our results suggest that childhood emotional abuse is associated with reduced hippocampus volume in males, but not in females. However, emotional abuse was associated with higher levels of subclinical psychopathology in both males and females. These data suggest that while females may be more resilient to the neurological effects of childhood maltreatment, they are not more resilient to the psychiatric symptoms associated with childhood maltreatment. Further research is needed to elucidate the mechanisms involved in these different levels of resilience. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Interaction between BDNF rs6265 Met allele and low family cohesion is associated with smaller left hippocampal volume in pediatric bipolar disorder.

    Science.gov (United States)

    Zeni, Cristian Patrick; Mwangi, Benson; Cao, Bo; Hasan, Khader M; Walss-Bass, Consuelo; Zunta-Soares, Giovana; Soares, Jair C

    2016-01-01

    Genetic and environmental factors are implicated in the onset and evolution of pediatric bipolar disorder, and may be associated to structural brain abnormalities. The aim of our study was to assess the impact of the interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism and family functioning on hippocampal volumes of children and adolescents with bipolar disorder, and typically-developing controls. We evaluated the family functioning cohesion subscale using the Family Environment Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural brain imaging in 29 children and adolescents with bipolar disorder, and 22 healthy controls. We did not find significant differences between patients with BD or controls in left or right hippocampus volume (p=0.44, and p=0.71, respectively). However, we detected a significant interaction between low scores on the cohesion subscale and the presence of the Met allele at BNDF on left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None of the factors independently (BDNF Val66Met, cohesion scores) was significantly associated with hippocampal volume differences. small sample size, cross-sectional study. These results may lead to a better understanding of the impact of the interaction between genes and environment factors on brain structures associated to bipolar disorder and its manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Acute 5-HT7 receptor activation increases NMDA-evoked currents and differentially alters NMDA receptor subunit phosphorylation and trafficking in hippocampal neurons.

    Science.gov (United States)

    Vasefi, Maryam S; Yang, Kai; Li, Jerry; Kruk, Jeff S; Heikkila, John J; Jackson, Michael F; MacDonald, John F; Beazely, Michael A

    2013-05-14

    N-methyl-D-aspartate (NMDA) receptors are regulated by several G protein-coupled receptors (GPCRs) as well as receptor tyrosine kinases. Serotonin (5-HT) type 7 receptors are expressed throughout the brain including the thalamus and hippocampus. Long-term (2-24 h) activation of 5-HT7 receptors promotes the expression of neuroprotective growth factor receptors, including the platelet-derived growth factor (PDGF) β receptors which can protect neurons against NMDA-induced neurotoxicity. In contrast to long-term activation of 5-HT7 receptors, acute (5 min) treatment of isolated hippocampal neurons with the 5-HT7 receptor agonist 5-carboxamidotryptamine (5-CT) enhances NMDA-evoked peak currents and this increase in peak currents is blocked by the 5-HT7 receptor antagonist, SB 269970. In hippocampal slices, acute 5-HT7 receptor activation increases NR1 NMDA receptor subunit phosphorylation and differentially alters the phosphorylation state of the NR2B and NR2A subunits. NMDA receptor subunit cell surface expression is also differentially altered by 5-HT7 receptor agonists: NR2B cell surface expression is decreased whereas NR1 and NR2A surface expression are not significantly altered. In contrast to the negative regulatory effects of long-term activation of 5-HT7 receptors on NMDA receptor signaling, acute activation of 5-HT7 receptors promotes NMDA receptor activity. These findings highlight the potential for temporally differential regulation of NMDA receptors by the 5-HT7 receptor.

  12. Identification of common variants associated with human hippocampal and intracranial volumes

    NARCIS (Netherlands)

    Stein, J.L.; Medland, S.E.; Arias-Vasquez, A.; Hibar, D.P.; Senstad, R.E.; Winkler, A.M.; Toro, R.; Appel, K.; Bartecek, R.; Bergmann, O.; Hottenga, J.J.; Boomsma, D.I.; Montgomery, G.W.; de Geus, E.J.C.; Hulshoff Pol, H.E.; Kahn, R.S.; Penninx, B.W.J.H.; Sämann, P.G.; Saykin, A.J.; Schumann, G.; Smoller, J.W.; Wardlaw, J.M.; Weale, M.E.; Martin, N.G.; Franke, B.; Wright, M.J.; Thompson, P.M.

    2012-01-01

    Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal

  13. Identification of common variants associated with human hippocampal and intracranial volumes.

    NARCIS (Netherlands)

    Stein, J.L.; Medland, S.E.; Arias Vasquez, A.; Hibar, D.P.; Senstad, R.E.; Winkler, A.M.; Toro, R.; Appel, K.; Bartecek, R.; Bergmann, O.; Bernard, M.; Brown, A.A.; Cannon, D.M.; Chakravarty, M.M.; Christoforou, A.; Domin, M.; Grimm, O.; Hollinshead, M.; Holmes, A.J.; Homuth, G.; Hottenga, J.J.; Langan, C.; Lopez, L.M.; Hansell, N.K.; Hwang, K.S.; Kim, S.; Laje, G.; Lee, P.H.; Liu, X.; Loth, E.; Lourdusamy, A.; Mattingsdal, M.; Mohnke, S.; Maniega, S.M.; Nho, K.; Nugent, A.C.; O'Brien, C.; Papmeyer, M.; Putz, B.; Ramasamy, A.; Rasmussen, J.; Rijpkema, M.J.P.; Risacher, S.L.; Roddey, J.C.; Rose, E.J.; Ryten, M.; Shen, L.; Sprooten, E.; Strengman, E.; Teumer, A.; Trabzuni, D.; Turner, J.; Eijk, K. van; Erp, T.G. van; Tol, M.J. van; Wittfeld, K.; Wolf, C. de; Woudstra, S.; Aleman, A.; Alhusaini, S.; Almasy, L.; Binder, E.B.; Brohawn, D.G.; Cantor, R.M.; Carless, M.A.; Corvin, A.; Czisch, M.; Curran, J.E.; Davies, G.; Almeida, M.A. de; Delanty, N.; Depondt, C.; Duggirala, R.; Dyer, T.D.; Erk, S.; Fagerness, J.; Fox, P.T.; Freimer, N.B.; Gill, M.; Goring, H.H.; Hagler, D.J.; Hoehn, D.; Holsboer, F.; Hoogman, M.; Hosten, N.; Jahanshad, N.; Johnson, M.P.; Kasperaviciute, D.; Kent Jr., J.W.; Kochunov, P.; Lancaster, J.L.; Lawrie, S.M.; Liewald, D.C.; Mandl, R.C.W.; Matarin, M.; Mattheisen, M.; Meisenzahl, E.; Melle, I.; Moses, E.K.; Muhleisen, T.W.; Nauck, M.; Nothen, Markus; Olvera, R.L.; Pandolfo, M.; Pike, G.B.; Puls, R.; Reinvang, I.; Renteria, M.E.; Rietschel, M.; Roffman, J.L.; Royle, N.A.; Rujescu, D.; Savitz, J.; Schnack, H.G.; Schnell, K.; Seiferth, N.; Smith, C.; Steen, V.M.; Valdes Hernandez, M.C.; Heuvel, M. van den; Wee, N.J. van der; Haren, N.E.M. van; Veltman, J.A.; Volzke, H.; Walker, R.; Westlye, L.T.; Whelan, C.D.; Agartz, I.; Boomsma, D.I.; Cavalleri, G.L.; Dale, A.M.; Djurovic, S.; Drevets, W.C.; Hagoort, P.; Hall, J.; Heinz, A.; Jack Jr., C.R.; Foroud, T.M.; Hellard, S. Le; Macciardi, F.; Montgomery, G.W.; Poline, J.B.; Porteous, D.J.; Sisodiya, S.M.; Starr, J.M.; Sussmann, J.; Toga, A.W.; Veltman, D.J.; Walter, H.; Weiner, M.W.; Bis, J.C.; Ikram, M.A.; Smith, A.V.; Gudnason, V.; Tzourio, C.; Vernooij, M.W.; Launer, L.J.; DeCarli, C.; Seshadri, S.; Andreassen, O.A.; Apostolova, L.G.; Bastin, M.E.; Blangero, J.; Brunner, H.G.; Buckner, R.L.; Cichon, S.; Coppola, G.; Zubicaray, G.I. de; Deary, I.J.; Donohoe, G.; Geus, E.J. de; Espeseth, T.; Fernandez, G.S.E.; Glahn, D.C.; Grabe, H.J.; Hardy, J.; Hulshoff Pol, H.E.; Jenkinson, M.; Kahn, R.S.; McDonald, C.; McIntosh, A.M.; McMahon, F.J.; McMahon, K.L.; Meyer-Lindenberg, A.; Morris, D.W.; Muller-Myhsok, B.; Nichols, T.E.; Ophoff, R.A.; Paus, T.; Pausova, Z.; Penninx, B.W.J.H.; Potkin, S.G.; Samann, P.G.; Saykin, A.J.; Schumann, G.; Smoller, J.W.; Wardlaw, J.M.; Weale, M.E.; Martin, N.G.; Franke, B.; Wright, M.J.; Thompson, P.M.; Klaasen, A.; et al.,

    2012-01-01

    Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal

  14. Automated cross-sectional and longitudinal hippocampal volume measurement in mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Leung, Kelvin K; Barnes, Josephine; Ridgway, Gerard R; Bartlett, Jonathan W; Clarkson, Matthew J; Macdonald, Kate; Schuff, Norbert; Fox, Nick C; Ourselin, Sebastien

    2010-07-15

    Volume and change in volume of the hippocampus are both important markers of Alzheimer's disease (AD). Delineation of the structure on MRI is time-consuming and therefore reliable automated methods are required. We describe an improvement (multiple-atlas propagation and segmentation (MAPS)) to our template library-based segmentation technique. The improved technique uses non-linear registration of the best-matched templates from our manually segmented library to generate multiple segmentations and combines them using the simultaneous truth and performance level estimation (STAPLE) algorithm. Change in volume over 12months (MAPS-HBSI) was measured by applying the boundary shift integral using MAPS regions. Methods were developed and validated against manual measures using subsets from Alzheimer's Disease Neuroimaging Initiative (ADNI). The best method was applied to 682 ADNI subjects, at baseline and 12-month follow-up, enabling assessment of volumes and atrophy rates in control, mild cognitive impairment (MCI) and AD groups, and within MCI subgroups classified by subsequent clinical outcome. We compared our measures with those generated by Surgical Navigation Technologies (SNT) available from ADNI. The accuracy of our volumes was one of the highest reported (mean(SD) Jaccard Index 0.80(0.04) (N=30)). Both MAPS baseline volume and MAPS-HBSI atrophy rate distinguished between control, MCI and AD groups. Comparing MCI subgroups (reverters, stable and converters): volumes were lower and rates higher in converters compared with stable and reverter groups (pmethods give accurate and reliable volumes and atrophy rates across the clinical spectrum from healthy aging to AD. Copyright 2010 Elsevier Inc. All rights reserved.

  15. A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

    OpenAIRE

    Stomby, Andreas; Otten, Julia; Ryberg, Mats; Nyberg, Lars; Olsson, Tommy; Boraxbekk, Carl-Johan

    2017-01-01

    Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume wa...

  16. Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression

    Science.gov (United States)

    Raghavan, Neha S.; Chen, Hao; Schipma, Matthew; Luo, Wendy; Chung, Sarah; Wang, Lei; Redei, Eva E.

    2018-01-01

    Major depressive disorder (MDD) is a debilitating illness that affects twice as many women than men postpuberty. This female bias is thought to be caused by greater heritability of MDD in women and increased vulnerability induced by female sex hormones. We tested this hypothesis by removing the ovaries from prepubertal Wistar Kyoto (WKY) more immobile (WMI) females, a genetic animal model of depression, and its genetically close control, the WKY less immobile (WLI). In adulthood, prepubertally ovariectomized (PrePubOVX) animals and their Sham-operated controls were tested for depression- and anxiety-like behaviors, using the routinely employed forced swim and open field tests, respectively, and RNA-sequencing was performed on their hippocampal RNA. Our results confirmed that the behavioral and hippocampal expression changes that occur after prepubertal ovariectomy are the consequences of an interaction between genetic predisposition to depressive behavior and ovarian hormone-regulated processes. Lack of ovarian hormones during and after puberty in the WLIs led to increased depression-like behavior. In WMIs, both depression- and anxiety-like behaviors worsened by prepubertal ovariectomy. The unbiased exploration of the hippocampal transcriptome identified sets of differentially expressed genes (DEGs) between the strains and treatment groups. The relatively small number of hippocampal DEGs resulting from the genetic differences between the strains confirmed the genetic relatedness of these strains. Nevertheless, the differences in DEGs between the strains in response to prepubertal ovariectomy identified different molecular processes, including the importance of glucocorticoid receptor-mediated mechanisms, that may be causative of the increased depression-like behavior in the presence or absence of genetic predisposition. This study contributes to the understanding of hormonal maturation-induced changes in affective behaviors and the hippocampal transcriptome as it

  17. Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression

    Directory of Open Access Journals (Sweden)

    Neha S. Raghavan

    2018-01-01

    Full Text Available Major depressive disorder (MDD is a debilitating illness that affects twice as many women than men postpuberty. This female bias is thought to be caused by greater heritability of MDD in women and increased vulnerability induced by female sex hormones. We tested this hypothesis by removing the ovaries from prepubertal Wistar Kyoto (WKY more immobile (WMI females, a genetic animal model of depression, and its genetically close control, the WKY less immobile (WLI. In adulthood, prepubertally ovariectomized (PrePubOVX animals and their Sham-operated controls were tested for depression- and anxiety-like behaviors, using the routinely employed forced swim and open field tests, respectively, and RNA-sequencing was performed on their hippocampal RNA. Our results confirmed that the behavioral and hippocampal expression changes that occur after prepubertal ovariectomy are the consequences of an interaction between genetic predisposition to depressive behavior and ovarian hormone-regulated processes. Lack of ovarian hormones during and after puberty in the WLIs led to increased depression-like behavior. In WMIs, both depression- and anxiety-like behaviors worsened by prepubertal ovariectomy. The unbiased exploration of the hippocampal transcriptome identified sets of differentially expressed genes (DEGs between the strains and treatment groups. The relatively small number of hippocampal DEGs resulting from the genetic differences between the strains confirmed the genetic relatedness of these strains. Nevertheless, the differences in DEGs between the strains in response to prepubertal ovariectomy identified different molecular processes, including the importance of glucocorticoid receptor-mediated mechanisms, that may be causative of the increased depression-like behavior in the presence or absence of genetic predisposition. This study contributes to the understanding of hormonal maturation-induced changes in affective behaviors and the hippocampal

  18. Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction.

    Science.gov (United States)

    Chengyang, Li; Daqing, Huang; Jianlin, Qi; Haisheng, Chang; Qingqing, Meng; Jin, Wang; Jiajia, Liu; Enmao, Ye; Yongcong, Shao; Xi, Zhang

    2017-08-01

    Acute sleep restriction heavily influences cognitive function, affecting executive processes such as attention, response inhibition, and memory. Previous neuroimaging studies have suggested a link between hippocampal activity and short-term memory function. However, the specific contribution of the hippocampus to the decline of short-term memory following sleep restriction has yet to be established. In the current study, we utilized resting-state functional magnetic resonance imaging (fMRI) to examine the association between hippocampal functional connectivity (FC) and the decline of short-term memory following total sleep deprivation (TSD). Twenty healthy adult males aged 20.9 ± 2.3 years (age range, 18-24 years) were enrolled in a within-subject crossover study. Short-term memory and FC were assessed using a Delay-matching short-term memory test and a resting-state fMRI scan before and after TSD. Seed-based correlation analysis was performed using fMRI data for the left and right hippocampus to identify differences in hippocampal FC following TSD. Subjects demonstrated reduced alertness and a decline in short-term memory performance following TSD. Moreover, fMRI analysis identified reduced hippocampal FC with the superior frontal gyrus (SFG), temporal regions, and supplementary motor area. In addition, an increase in FC between the hippocampus and bilateral thalamus was observed, the extent of which correlated with short-term memory performance following TSD. Our findings indicate that the disruption of hippocampal-cortical connectivity is linked to the decline in short-term memory observed after acute sleep restriction. Such results provide further evidence that support the cognitive impairment model of sleep deprivation.

  19. GSK-3β Overexpression Alters the Dendritic Spines of Developmentally Generated Granule Neurons in the Mouse Hippocampal Dentate Gyrus

    Science.gov (United States)

    Pallas-Bazarra, Noemí; Kastanauskaite, Asta; Avila, Jesús; DeFelipe, Javier; Llorens-Martín, María

    2017-01-01

    The dentate gyrus (DG) plays a crucial role in hippocampal-related memory. The most abundant cellular type in the DG, namely granule neurons, are developmentally generated around postnatal day P6 in mice. Moreover, a unique feature of the DG is the occurrence of adult hippocampal neurogenesis, a process that gives rise to newborn granule neurons throughout life. Adult-born and developmentally generated granule neurons share some maturational aspects but differ in others, such as in their positioning within the granule cell layer. Adult hippocampal neurogenesis encompasses a series of plastic changes that modify the function of the hippocampal trisynaptic network. In this regard, it is known that glycogen synthase kinase 3β (GSK-3β) regulates both synaptic plasticity and memory. By using a transgenic mouse overexpressing GSK-3β in hippocampal neurons, we previously demonstrated that the overexpression of this kinase has deleterious effects on the maturation of newborn granule neurons. In the present study, we addressed the effects of GSK-3β overexpression on the morphology and number of dendritic spines of developmentally generated granule neurons. To this end, we performed intracellular injections of Lucifer Yellow in developmentally generated granule neurons of wild-type and GSK-3β-overexpressing mice and analyzed the number and morphologies of dendritic spines (namely, stubby, thin and mushroom). GSK-3β overexpression led to a general reduction in the number of dendritic spines. In addition, it caused a slight reduction in the percentage, head diameter and length of thin spines, whereas the head diameter of mushroom spines was increased. PMID:28344548

  20. Hippocampal volume change measurement: quantitative assessment of the reproducibility of expert manual outlining and the automated methods FreeSurfer and FIRST.

    Science.gov (United States)

    Mulder, Emma R; de Jong, Remko A; Knol, Dirk L; van Schijndel, Ronald A; Cover, Keith S; Visser, Pieter J; Barkhof, Frederik; Vrenken, Hugo

    2014-05-15

    To measure hippocampal volume change in Alzheimer's disease (AD) or mild cognitive impairment (MCI), expert manual delineation is often used because of its supposed accuracy. It has been suggested that expert outlining yields poorer reproducibility as compared to automated methods, but this has not been investigated. To determine the reproducibilities of expert manual outlining and two common automated methods for measuring hippocampal atrophy rates in healthy aging, MCI and AD. From the Alzheimer's Disease Neuroimaging Initiative (ADNI), 80 subjects were selected: 20 patients with AD, 40 patients with mild cognitive impairment (MCI) and 20 healthy controls (HCs). Left and right hippocampal volume change between baseline and month-12 visit was assessed by using expert manual delineation, and by the automated software packages FreeSurfer (longitudinal processing stream) and FIRST. To assess reproducibility of the measured hippocampal volume change, both back-to-back (BTB) MPRAGE scans available for each visit were analyzed. Hippocampal volume change was expressed in μL, and as a percentage of baseline volume. Reproducibility of the 1-year hippocampal volume change was estimated from the BTB measurements by using linear mixed model to calculate the limits of agreement (LoA) of each method, reflecting its measurement uncertainty. Using the delta method, approximate p-values were calculated for the pairwise comparisons between methods. Statistical analyses were performed both with inclusion and exclusion of visibly incorrect segmentations. Visibly incorrect automated segmentation in either one or both scans of a longitudinal scan pair occurred in 7.5% of the hippocampi for FreeSurfer and in 6.9% of the hippocampi for FIRST. After excluding these failed cases, reproducibility analysis for 1-year percentage volume change yielded LoA of ±7.2% for FreeSurfer, ±9.7% for expert manual delineation, and ±10.0% for FIRST. Methods ranked the same for reproducibility of 1

  1. Developmental Differences in Relations between Episodic Memory and Hippocampal Subregion Volume during Early Childhood

    Science.gov (United States)

    Riggins, Tracy; Blankenship, Sarah L.; Mulligan, Elizabeth; Rice, Katherine; Redcay, Elizabeth

    2015-01-01

    Episodic memory shows striking improvement during early childhood. However, neural contributions to these behavioral changes are not well understood. This study examined associations between episodic memory and volume of subregions (head, body, and tail) of the hippocampus--a structure known to support episodic memory in school-aged children and…

  2. Identification of common variants associated with human hippocampal and intracranial volumes

    NARCIS (Netherlands)

    Stein, Jason L.; Medland, Sarah E.; Vasquez, Alejandro Arias; Hibar, Derrek P.; Senstad, Rudy E.; Winkler, Anderson M.; Toro, Roberto; Appel, Katja; Bartecek, Richard; Bergmann, Orjan; Bernard, Manon; Brown, Andrew A.; Cannon, Dara M.; Chakravarty, M. Mallar; Christoforou, Andrea; Domin, Martin; Grimm, Oliver; Hollinshead, Marisa; Holmes, Avram J.; Homuth, Georg; Hottenga, Jouke-Jan; Langan, Camilla; Lopez, Lorna M.; Hansell, Narelle K.; Hwang, Kristy S.; Kim, Sungeun; Laje, Gonzalo; Lee, Phil H.; Liu, Xinmin; Loth, Eva; Lourdusamy, Anbarasu; Mattingsdal, Morten; Mohnke, Sebastian; Maniega, Susana Munoz; Nho, Kwangsik; Nugent, Allison C.; O'Brien, Carol; Papmeyer, Martina; Putz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rijpkema, Mark; Risacher, Shannon L.; Roddey, J. Cooper; Rose, Emma J.; Ryten, Mina; Shen, Li; Sprooten, Emma; Strengman, Eric; Teumer, Alexander; Trabzuni, Daniah; Turner, Jessica; van Eijk, Kristel; van Erp, Theo G. M.; van Tol, Marie-Jose; Wittfeld, Katharina; Wolf, Christiane; Woudstra, Saskia; Aleman, Andre; Alhusaini, Saud; Almasy, Laura; Binder, Elisabeth B.; Brohawn, David G.; Cantor, Rita M.; Carless, Melanie A.; Corvin, Aiden; Czisch, Michael; Curran, Joanne E.; Davies, Gail; de Almeida, Marcio A. A.; Delanty, Norman; Depondt, Chantal; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fagerness, Jesen; Fox, Peter T.; Freimer, Nelson B.; Gill, Michael; Goering, Harald H. H.; Hagler, Donald J.; Hoehn, David; Holsboer, Florian; Hoogman, Martine; Hosten, Norbert; Jahanshad, Neda; Johnson, Matthew P.; Kasperaviciute, Dalia; Kent, Jack W.; Kochunov, Peter; Lancaster, Jack L.; Lawrie, Stephen M.; Liewald, David C.; Mandl, Rene; Matarin, Mar; Mattheisen, Manuel; Meisenzahl, Eva; Melle, Ingrid; Moses, Eric K.; Muehleisen, Thomas W.; Nauck, Matthias; Noethen, Markus M.; Olvera, Rene L.; Pandolfo, Massimo; Pike, G. Bruce; Puls, Ralf; Reinvang, Ivar; Renteria, Miguel E.; Rietschel, Marcella; Roffman, Joshua L.; Royle, Natalie A.; Rujescu, Dan; Savitz, Jonathan; Schnack, Hugo G.; Schnell, Knut; Seiferth, Nina; Smith, Colin; Steen, Vidar M.; Hernandez, Maria C. Valdes; Van den Heuvel, Martijn; van der Wee, Nic J.; Van Haren, Neeltje E. M.; Veltman, Joris A.; Voelzke, Henry; Walker, Robert; Westlye, Lars T.; Whelan, Christopher D.; Agartz, Ingrid; Boomsma, Dorret I.; Cavalleri, Gianpiero L.; Dale, Anders M.; Djurovic, Srdjan; Drevets, Wayne C.; Hagoort, Peter; Hall, Jeremy; Heinz, Andreas; Jack, Clifford R.; Foroud, Tatiana M.; Le Hellard, Stephanie; Macciardi, Fabio; Montgomery, Grant W.; Poline, Jean Baptiste; Porteous, David J.; Sisodiya, Sanjay M.; Starr, John M.; Sussmann, Jessika; Toga, Arthur W.; Veltman, Dick J.; Walter, Henrik; Weiner, Michael W.; Bis, Joshua C.; Ikram, M. Arfan; Smith, Albert V.; Gudnason, Vilmundur; Tzourio, Christophe; Vernooij, Meike W.; Launer, Lenore J.; DeCarli, Charles; Seshadri, Sudha; Andreassen, Ole A.; Apostolova, Liana G.; Bastin, Mark E.; Blangero, John; Brunner, Han G.; Buckner, Randy L.; Cichon, Sven; Coppola, Giovanni; de Zubicaray, Greig I.; Deary, Ian J.; Donohoe, Gary; de Geus, Eco J. C.; Espeseth, Thomas; Fernandez, Guillen; Glahn, David C.; Grabe, Hans J.; Hardy, John; Pol, Hilleke E. Hulshoff; Jenkinson, Mark; Kahn, Rene S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Meyer-Lindenberg, Andreas; Morris, Derek W.; Mueller-Myhsok, Bertram; Nichols, Thomas E.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W.; Potkin, Steven G.; Saemann, Philipp G.; Saykin, Andrew J.; Schumann, Gunter; Smoller, Jordan W.; Wardlaw, Joanna M.; Weale, Michael E.; Martin, Nicholas G.; Franke, Barbara; Wright, Margaret J.; Thompson, Paul M.

    Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease(1,2) and is reduced in schizophrenia(3), major depression(4) and

  3. Hippocampal volume is positively associated with behavioural inhibition (BIS) in a large community-based sample of mid-life adults: the PATH through life study.

    Science.gov (United States)

    Cherbuin, Nicolas; Windsor, Tim D; Anstey, Kaarin J; Maller, Jerome J; Meslin, Chantal; Sachdev, Perminder S

    2008-09-01

    The fields of personality research and neuropsychology have developed with very little overlap. Gray and McNaughton were among the first to recognize that personality traits must have neurobiological correlates and developed models relating personality factors to brain structures. Of particular note was their description of associations between conditioning, inhibition and activation of behaviours, and specific neural structures such as the hippocampus, amygdala and the prefrontal cortex. The aim of this study was to determine whether personality constructs representing the behavioural inhibition and activation systems (BIS/BAS) were associated with volumetric measures of the hippocampus and amygdala in humans. Amygdalar and hippocampal volumes were measured in 430 brain scans of cognitively intact community-based volunteers. Linear associations between brain volumes and the BIS/BAS measures were assessed using multiple regression, controlling for age, sex, education, intra-cranial and total brain volume. Results showed that hippocampal volumes were positively associated with BIS sensitivity and to a lesser extent with BAS sensitivity. No association was found between amygdalar volume and either the BIS or BAS. These findings add support to the model of Gray and McNaughton, which proposes a role of the hippocampus in the regulation of defensive/approach behaviours and trait anxiety but suggest an absence of associations between amygdala volume and BIS/BAS measures.

  4. Verbal and visual memory performance and hippocampal volumes, measured by 3-Tesla magnetic resonance imaging, in patients with Cushing's syndrome.

    Science.gov (United States)

    Resmini, Eugenia; Santos, Alicia; Gómez-Anson, Beatriz; Vives, Yolanda; Pires, Patricia; Crespo, Iris; Portella, Maria J; de Juan-Delago, Manel; Barahona, Maria-José; Webb, Susan M

    2012-02-01

    Cushing's syndrome (CS) affects cognition and memory. Our objective was to evaluate memory and hippocampal volumes (HV) on 3-tesla magnetic resonance imaging (3T MRI) in CS patients and controls. Thirty-three CS patients (11 active, 22 cured) and 34 controls matched for age, sex, and education underwent Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex Figure memory tests. Gray matter and HV were calculated on 3T MRI, using FreeSurfer image analyses software. No differences in HV were observed between active and cured CS or controls. Memory performance was worse in CS patients than controls (P visual memory (P = 0.04) than controls. In 12 CS patients, memory was below normative cutoff values for verbal (n = 6, cured), visual memory (n = 10, six cured) or both (n = 4); these patients with severe memory impairments showed smaller HV compared with their matched controls (P = 0.02 with verbal impairment; P = 0.03 with visual impairment). They were older (P = 0.04), had shorter education (P = 0.02), and showed a trend toward longer duration of hypercortisolism (P = 0.07) than the remaining CS patients. Total (P = 0.004) and cortical (P = 0.03) brain gray matter volumes were decreased in CS compared with controls, indicating brain atrophy, whereas subcortical gray matter (which includes HV) was reduced only in the 12 patients with severe memory impairment. Verbal and visual memory is worse in CS patients than controls, even after biochemical cure. HV was decreased only in those whose memory scores were below normative cutoff values.

  5. Interplay of hippocampal volume and hypothalamus-pituitary-adrenal axis function as markers of stress vulnerability in men at ultra-high risk for psychosis.

    Science.gov (United States)

    Pruessner, M; Bechard-Evans, L; Pira, S; Joober, R; Collins, D L; Pruessner, J C; Malla, A K

    2017-02-01

    Altered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results. Study participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol. Cortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size). Our findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.

  6. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic...... enzyme NSE, suggesting increased anaerobic metabolism. Neuronal cell adhesion molecule (NCAM) decreased in pyriform cortex and amygdala of kindled rats, indicating neuronal degeneration....

  7. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze

    OpenAIRE

    Hernández-Pérez, J. Jesús; Gutiérrez-Guzmán, Blanca E.; López-Vázquez, Miguel Á.; Olvera-Cortés, María E.

    2015-01-01

    Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which a...

  8. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze.

    OpenAIRE

    Jesús J. Hernández-Pérez; Blanca Erika Gutiérrez-Guzmán; Miguel Ángel López-Vázquez; Miguel Ángel López-Vázquez; María Esther Olvera-Cortés

    2015-01-01

    Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which a...

  9. Lateralized hippocampal volume increase following high-frequency left prefrontal repetitive transcranial magnetic stimulation in patients with major depression.

    Science.gov (United States)

    Hayasaka, Shunsuke; Nakamura, Motoaki; Noda, Yoshihiro; Izuno, Takuji; Saeki, Takashi; Iwanari, Hideo; Hirayasu, Yoshio

    2017-11-01

    Repetitive transcranial magnetic stimulation (rTMS) has been applied as a treatment for patients with treatment-resistant depression in recent years, and a large body of evidence has demonstrated its therapeutic efficacy through stimulating neuronal plasticity. The aim of this study was to investigate structural alterations in the hippocampus (HIPP) and amygdala (AM) following conventional rTMS in patients with depression. Twenty-eight patients with depression underwent 10 daily 20-Hz left prefrontal rTMS over 2 weeks. The left dorsolateral prefrontal cortex (DLPFC) was identified using magnetic resonance imaging-guided neuronavigation prior to stimulation. Magnetic resonance imaging scans were obtained at baseline and after the completion of rTMS sessions. The therapeutic effects of rTMS were evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D 17 ), and the volumes of the HIPP and AM were measured by a manual tracing method. Statistical analyses revealed a significant volume increase in the left HIPP (+3.4%) after rTMS but no significant volume change in the AM. No correlation was found between the left HIPP volume increase and clinical improvement, as measured by the HAM-D 17 . The present study demonstrated that conventional left prefrontal rTMS increases the HIPP volume in the stimulated side, indicating a remote neuroplastic effect through the cingulum bundle. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

  10. Altered Synaptic Marker Abundance in the Hippocampal Stratum Oriens of Ts65Dn Mice is Associated with Exuberant Expression of Versican

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    Matthew D Howell

    2012-01-01

    Full Text Available DS (Down syndrome, resulting from trisomy of chromosome 21, is the most common cause of genetic mental retardation; however, the molecular mechanisms underlying the cognitive deficits are poorly understood. Growing data indicate that changes in abundance or type of CSPGs (chondroitin sulfate proteoglycans in the ECM (extracellular matrix can influence synaptic structure and plasticity. The purpose of this study was to identify changes in synaptic structure in the hippocampus in a model of DS, the Ts65Dn mouse, and to determine the relationship to proteoglycan abundance and/or cleavage and cognitive disability. We measured synaptic proteins by ELISA and changes in lectican expression and processing in the hippocampus of young and old Ts65Dn mice and LMCs (littermate controls. In young (5 months old Ts65Dn hippocampal extracts, we found a significant increase in the postsynaptic protein PSD-95 (postsynaptic density 95 compared with LMCs. In aged (20 months old Ts65Dn hippocampus, this increase was localized to hippocampal stratum oriens extracts compared with LMCs. Aged Ts65Dn mice exhibited impaired hippocampal-dependent spatial learning and memory in the RAWM (radial-arm water maze and a marked increase in levels of the lectican versican V2 in stratum oriens that correlated with the number of errors made in the final RAWM block. Ts65Dn stratum oriens PNNs (perineuronal nets, an extension of the ECM enveloping mostly inhibitory interneurons, were dispersed over a larger area compared with LMC mice. Taken together, these data suggest a possible association with alterations in the ECM and inhibitory neurotransmission in the Ts65Dn hippocampus which could contribute to cognitive deficits.

  11. Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI.

    Science.gov (United States)

    Waddell, Jaylyn; Hanscom, Marie; Shalon Edwards, N; McKenna, Mary C; McCarthy, Margaret M

    2016-01-01

    Hypoxia-ischemia (HI) of the brain in near-term and term infants is a leading cause of infant mortality and lifelong disability but current therapeutic approaches remain limited. Males consistently display greater vulnerability to the deleterious consequences of HI in both humans and animal models. Neurogenesis increases after neonatal HI and offers a potential therapeutic target for recovery. The steroid hormone estradiol has been extensively explored as a neuroprotectant in adult models of stroke but with mixed results. Less consideration has been afforded to this naturally occurring agent in the developing brain, which has unique challenges from the adult. Using a model of term HI in the rat we have explored the impact of this insult on cell genesis in the hippocampus of males and females and the ability of estradiol treatment immediately after insult to restore function. Both short-term (3 days) and long-term (7 days) post-injury were assessed and revealed that only females had markedly increased cell genesis on the short-term but both sexes were increased long-term. A battery of behavioral tests revealed motor impairment in males and compromised episodic memory while both sexes were modestly impaired in spatial memory. Juvenile social play was also depressed in both sexes after HI. Estradiol therapy improved behavioral performance in both sexes but did not reverse a deficit in hippocampal volume ipsilateral to the insult. Thus the effects of estradiol do not appear to be via cell death or proliferation but rather involve other components of neural functioning. Published by Elsevier Inc.

  12. Altered NMDA receptor function in primary cultures of hippocampal neurons from mice lacking the Homer2 gene.

    Science.gov (United States)

    Smothers, C Thetford; Szumlinski, Karen K; Worley, Paul F; Woodward, John J

    2016-01-01

    N-Methyl-D-Aspartate (NMDA) receptors are inhibited during acute exposure to ethanol and are involved in changes in neuronal plasticity following repeated ethanol exposure. The postsynaptic scaffolding protein Homer2 can regulate the cell surface expression of NMDA receptors in vivo, and mice with a null mutation of the Homer2 gene exhibit an alcohol-avoiding and -intolerant phenotype that is accompanied by a lack of ethanol-induced glutamate sensitization. Thus, Homer2 deletion may perturb the function or acute ethanol sensitivity of the NMDA receptor. In this study, the function and ethanol sensitivity of glutamate receptors in cultured hippocampal neurons from wild-type (WT) and Homer2 knock-out (KO) mice were examined at 7 and 14 days in vitro (DIV) using standard whole-cell voltage-clamp electrophysiology. As compared with wild-type controls, NMDA receptor current density was reduced in cultured hippocampal neurons from Homer2 KO mice at 14 DIV, but not at 7 DIV. There were no genotype-dependent changes in whole-cell capacitance or in currents evoked by kainic acid. The GluN2B-selective antagonist ifenprodil inhibited NMDA-evoked currents to a similar extent in both wild-type and Homer2 KO neurons and inhibition was greater at 7 versus 14 DIV. NMDA receptor currents from both WT and KO mice were inhibited by ethanol (10-100 mM) and the degree of inhibition did not differ as a function of genotype. In conclusion, NMDA receptor function, but not ethanol sensitivity, is reduced in hippocampal neurons lacking the Homer2 gene. © 2015 Wiley Periodicals, Inc.

  13. The neurotoxin 1-methyl-4-phenylpyridinium (MPP+ alters hippocampal excitatory synaptic transmission by modulation of the GABAergic system

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    YuYing eHuang

    2015-08-01

    Full Text Available The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP induces Parkinson’s disease (PD-like symptoms following administration to mice, monkeys and humans. A common view is that MPTP is metabolized to 1-methyl-4-phenylpyridinium ion (MPP+ to induce its neurodegenerative effects on dopaminergic neurons in the substantia nigra. Moreover, the hippocampus contains dopaminergic fibers, which are projecting from the ventral tegmental area, substantia nigra and pars compacta and contain the whole machinery required for dopamine synthesis making them sensitive to MPTP and MPP+. Here we present data showing that acute bath-application of MPP+ elicited a dose-dependent facilitation followed by a depression of synaptic transmission of hippocampal Schaffer collaterals-CA1 synapses in mice. The effects of MPP+ were not mediated by D1/D5- and D2-like receptor activation. Inhibition of the dopamine transporters (DAT did not prevent but increased the depression of excitatory postsynaptic field potentials. In the search for a possible mechanism, we observed that MPP+ reduced the appearance of polyspikes in population spikes recorded in str. pyramidale and increased the frequency of miniature inhibitory postsynaptic currents. The acute effect of MPP+ on synaptic transmission was attenuated by co-application of a GABAA receptor antagonist. Taking these data together, we suggest that MPP+ affects hippocampal synaptic transmission by enhancing some aspects of

  14. Computational study of hippocampal-septal theta rhythm changes due to β-amyloid-altered ionic channels.

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    Xin Zou

    Full Text Available Electroencephagraphy (EEG of many dementia patients has been characterized by an increase in low frequency field potential oscillations. One of the characteristics of early stage Alzheimer's disease (AD is an increase in theta band power (4-7 Hz. However, the mechanism(s underlying the changes in theta oscillations are still unclear. To address this issue, we investigate the theta band power changes associated with β-Amyloid (Aβ peptide (one of the main markers of AD using a computational model, and by mediating the toxicity of hippocampal pyramidal neurons. We use an established biophysical hippocampal CA1-medial septum network model to evaluate four ionic channels in pyramidal neurons, which were demonstrated to be affected by Aβ. They are the L-type Ca²⁺ channel, delayed rectifying K⁺ channel, A-type fast-inactivating K⁺ channel and large-conductance Ca²⁺-activated K⁺ channel. Our simulation results demonstrate that only the Aβ inhibited A-type fast-inactivating K⁺ channel can induce an increase in hippocampo-septal theta band power, while the other channels do not affect theta rhythm. We further deduce that this increased theta band power is due to enhanced synchrony of the pyramidal neurons. Our research may elucidate potential biomarkers and therapeutics for AD. Further investigation will be helpful for better understanding of AD-induced theta rhythm abnormalities and associated cognitive deficits.

  15. Genetic deletion of TREK-1 or TWIK-1/TREK-1 potassium channels does not alter the basic electrophysiological properties of mature hippocampal astrocytes in situ

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    Yixing eDu

    2016-02-01

    Full Text Available We have recently shown that a linear current-to-voltage (I-V relationship of membrane conductance (passive conductance reflects the intrinsic property of K+ channels in mature astrocytes. While passive conductance is known to underpin a highly negative and stable membrane potential (VM essential for the basic homeostatic function of astrocytes, a complete repertoire of the involved K+ channels remains elusive. TREK-1 two-pore domain K+ channel (K2P is highly expressed in astrocytes, and covalent association of TREK-1 with TWIK-1, another highly expressed astrocytic K2P, has been reported as a mechanism underlying the trafficking of this heterodimer channel to the membrane and contributing to astrocytes’ passive conductance. To decipher the individual contribution of TREK-1 and address whether the appearance of passive conductance is conditional to the co-expression of TWIK-1/TREK-1 in astrocytes, TREK-1 single and TWIK-1/TREK-1 double gene knockout mice were used in the present study. The relative quantity of mRNA encoding other astrocyte K+ channels, such as Kir4.1, Kir5.1, and TREK-2, was not altered in these gene knockout mice. Whole-cell recording from hippocampal astrocytes in situ revealed no detectable changes in astrocyte passive conductance, VM, or membrane input resistance (Rin in either kind of gene knockout mouse. Additionally, TREK-1 proteins were mainly located in the intracellular compartments of the hippocampus. Altogether, genetic deletion of TREK-1 alone or together with TWIK-1 produced no obvious alteration in the basic electrophysiological properties of hippocampal astrocytes. Thus, future research focusing on other K+ channels may shed light on this long-standing and important question in astrocyte physiology.

  16. Alterations in maxillary sinus volume among oral and nasal breathers.

    Science.gov (United States)

    Agacayak, Kamil Serkan; Gulsun, Belgin; Koparal, Mahmut; Atalay, Yusuf; Aksoy, Orhan; Adiguzel, Ozkan

    2015-01-02

    Oral breathing causes many changes in the facial anatomical structures in adult patients. In this study we aimed to determine the effects of long-term oral breathing (>5 years) on the maxillary sinus volumes among adult male patients. We accessed medical records of 586 patients who had undergone cone beam computed tomography (CBCT) for any reason between September 2013 and April 2014. Patients who had undergone cone-beam dental volumetric tomography scans for any reason and who had answered a questionnaire about breathing were screened retrospectively. Cone beam dental volumetric tomography (I-Cat, Imaging Sciences International, Hatfield, PA, USA) was used to take the images of the maxillo-facial area at a setting of 120 kVp and 3.7 mA. This study involved male patients older than 21 years of age. The study included a total of 239 male patients, of which 68 were oral breathers and 171 were nasal breathers. The mean age of the oral breathers was 48.4 years and that of the nasal breathers was 46.7 years and the difference was not statistically significant (p>0.05). The mean maxillary sinus volumes of the oral and nasal breathers were 9043.49±1987.90 and 10851.77±2769.37, respectively, and the difference in maxillary sinus volume between the 2 groups was statistically significant (poral breathers (>5 years) was significantly lower than in nasal breathers, but it remains unclear whether this is due to malfunctioning of the nasal cavity or due to the underlying pathological condition.

  17. Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats.

    Science.gov (United States)

    Zamberletti, Erica; Gabaglio, Marina; Grilli, Massimo; Prini, Pamela; Catanese, Alberto; Pittaluga, Anna; Marchi, Mario; Rubino, Tiziana; Parolaro, Daniela

    2016-09-01

    Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition. Poorer memory performance and psychotic-like behaviors were present after adolescent THC treatment in male rats, without alterations in the emotional component. At cellular level, the expression of the NMDA receptor subunit, GluN2B, as well as the levels of the AMPA subunits, GluA1 and GluA2, were significantly increased in hippocampal post-synaptic fractions from THC-exposed rats compared to controls. Furthermore, increases in the levels of the pre-synaptic marker, synaptophysin, and the post-synaptic marker, PSD95, were also present. Interestingly, KCl-induced [(3)H]D-ASP release from hippocampal synaptosomes, but not gliosomes, was significantly enhanced in THC-treated rats compared to controls. Moreover, in the same brain region, adolescent THC treatment also resulted in a persistent neuroinflammatory state, characterized by increased expression of the astrocyte marker, GFAP, increased levels of the pro-inflammatory markers, TNF-α, iNOS and COX-2, as well as a concomitant reduction of the anti-inflammatory cytokine, IL-10. Notably, none of these alterations was observed in the prefrontal cortex (PFC). Together with our previous findings in females, these data suggest that the sex-dependent detrimental effects induced by adolescent THC exposure on adult behavior may rely on its

  18. Impaired spatial pattern separation performance in temporal lobe epilepsy is associated with visuospatial memory deficits and hippocampal volume loss.

    Science.gov (United States)

    Reyes, Anny; Holden, Heather M; Chang, Yu-Hsuan A; Uttarwar, Vedang S; Sheppard, David P; DeFord, Nicole E; DeJesus, Shannon Yandall; Kansal, Leena; Gilbert, Paul E; McDonald, Carrie R

    2018-03-01

    Individuals with chronic temporal lobe epilepsy (TLE) experience episodic memory deficits that may be progressive in nature. These memory decrements have been shown to increase with the extent of hippocampal damage, a hallmark feature of TLE. Pattern separation, a neural computational mechanism thought to play a role in episodic memory formation, has been shown to be negatively affected by aging and in individuals with known hippocampal dysfunction. Despite the link between poor pattern separation performance and episodic memory deficits, behavioral pattern separation has not been examined in patients with TLE. We examined pattern separation performance in a group of 22 patients with medically-refractory TLE and 20 healthy adults, using a task hypothesized to measure spatial pattern separation with graded levels of spatial interference. We found that individuals with TLE showed less efficient spatial pattern separation performance relative to healthy adults. Poorer spatial pattern separation performance in TLE was associated with poorer visuospatial memory, but only under high interference conditions. In addition, left hippocampal atrophy was associated with poor performance in the high interference condition in TLE. These data suggest that episodic memory impairments in patients with chronic, refractory TLE may be partially due to less efficient pattern separation, which likely reflects their underlying hippocampal dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Cannabis-related hippocampal volumetric abnormalities specific to subregions in dependent users.

    Science.gov (United States)

    Chye, Yann; Suo, Chao; Yücel, Murat; den Ouden, Lauren; Solowij, Nadia; Lorenzetti, Valentina

    2017-07-01

    Cannabis use is associated with neuroanatomical alterations in the hippocampus. While the hippocampus is composed of multiple subregions, their differential vulnerability to cannabis dependence remains unknown. The objective of the study is to investigate gray matter alteration in each of the hippocampal subregions (presubiculum, subiculum, cornu ammonis (CA) subfields CA1-4, and dentate gyrus (DG)) as associated with cannabis use and dependence. A total of 35 healthy controls (HC), 22 non-dependent (CB-nondep), and 39 dependent (CB-dep) cannabis users were recruited. We investigated group differences in hippocampal subregion volumes between HC, CB-nondep, and CB-dep users. We further explored the association between CB use variables (age of onset of regular use, monthly use, lifetime use) and hippocampal subregions in CB-nondep and CB-dep users separately. The CA1, CA2/3, CA4/DG, as well as total hippocampal gray matter were reduced in volume in CB-dep but not in CB-nondep users, relative to HC. The right CA2/3 and CA4/DG volumes were also negatively associated with lifetime cannabis use in CB-dep users. Our results suggest a regionally and dependence-specific influence of cannabis use on the hippocampus. Hippocampal alteration in cannabis users was specific to the CA and DG regions and confined to dependent users.

  20. Enhanced Stress Response in 5-HT1AR Overexpressing Mice: Altered HPA Function and Hippocampal Long-Term Potentiation.

    Science.gov (United States)

    Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Díaz, Álvaro; Garro-Martínez, Emilio; Linge, Raquel; Castro, Elena; Haberzettl, Robert; Fink, Heidrun; Bert, Bettina; Brosda, Jan; Romero, Beatriz; Crespo-Facorro, Benedicto; Pazos, Ángel

    2017-11-15

    Postsynaptic 5-HT 1A receptors (5-HT 1A R) play an important role in anxiety and stress, although their contribution is still controversial. Previous studies report that mice overexpressing postsynaptic 5-HT 1A Rs show no changes in basal anxiety, though the influence of stress conditions has not been addressed yet. In this study, we used this animal model to evaluate the role of 5-HT 1A Rs in anxiety response after pre-exposure to an acute stressor. Under basal conditions, 5-HT 1A R overexpressing animals presented high corticosterone levels and a lower mineralocorticoid/glucocorticoid receptor ratio. After pre-exposure to a single stressor, they showed a high anxiety-like response, associated with a blunted increase in corticosterone levels and higher c-Fos activation in the prefrontal cortex. Moreover, these mice also presented a lack of downregulation of hippocampal long-term potentiation after stress exposure. Therefore, higher postsynaptic 5-HT 1A R activation might predispose to a high anxious phenotype and an impaired stress coping behavior.

  1. Early postnatal respiratory viral infection alters hippocampal neurogenesis, cell fate, and neuron morphology in the neonatal piglet.

    Science.gov (United States)

    Conrad, Matthew S; Harasim, Samantha; Rhodes, Justin S; Van Alstine, William G; Johnson, Rodney W

    2015-02-01

    Respiratory viral infections are common during the neonatal period in humans, but little is known about how early-life infection impacts brain development. The current study used a neonatal piglet model as piglets have a gyrencephalic brain with growth and development similar to human infants. Piglets were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) to evaluate how chronic neuroinflammation affects hippocampal neurogenesis and neuron morphology. Piglets in the neurogenesis study received one bromodeoxyuridine injection on postnatal day (PD) 7 and then were inoculated with PRRSV. Piglets were sacrificed at PD 28 and the number of BrdU+ cells and cell fate were quantified in the dentate gyrus. PRRSV piglets showed a 24% reduction in the number of newly divided cells forming neurons. Approximately 15% of newly divided cells formed microglia, but this was not affected by sex or PRRSV. Additionally, there was a sexual dimorphism of new cell survival in the dentate gyrus where males had more cells than females, and PRRSV infection caused a decreased survival in males only. Golgi impregnation was used to characterize dentate granule cell morphology. Sholl analysis revealed that PRRSV caused a change in inner granule cell morphology where the first branch point was extended further from the cell body. Males had more complex dendritic arbors than females in the outer granule cell layer, but this was not affected by PRRSV. There were no changes to dendritic spine density or morphology distribution. These findings suggest that early-life viral infection can impact brain development. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Hippocampal Gαq/₁₁ but not Gαo-coupled receptors are altered in aging.

    Science.gov (United States)

    McQuail, Joseph A; Davis, Kathleen N; Miller, Frances; Hampson, Robert E; Deadwyler, Samuel A; Howlett, Allyn C; Nicolle, Michelle M

    2013-07-01

    Normal aging may limit the signaling efficacy of certain GPCRs by disturbing the function of specific Gα-subunits and leading to deficient modulation of intracellular functions that subserve synaptic plasticity, learning and memory. Evidence suggests that Gαq/₁₁ is more sensitive to the effects of aging relative to other Gα-subunits, including Gαo. To test this hypothesis, the functionality of Gαq/₁₁ and Gαo were compared in the hippocampus of young (6 months) and aged (24 months) F344 × BNF₁ hybrid rats assessed for spatial learning ability. Basal GTPγS-binding to Gαq/₁₁ was significantly elevated in aged rats relative to young and but not reliably associated with spatial learning. mAChR stimulation of Gαq/₁₁ with oxotremorine-M produced equivocal GTPγS-binding between age groups although values tended to be lower in the aged hippocampus and were inversely related to basal activity. Downstream Gαq/₁₁ function was measured in hippocampal subregion CA₁ by determining changes in [Ca(2+)]i after mAChR and mGluR (DHPG) stimulation. mAChR-stimulated peak change in [Ca(2+)]i was lower in aged CA₁ relative to young while mGluR-mediated integrated [Ca(2+)]i responses tended to be larger in aged. GPCR modulation of [Ca(2+)]i was observed to depend on intracellular stores to a greater degree in aged than young. In contrast, measures of Gαo-mediated GTPγS-binding were stable across age, including basal, mAChR-, GABABR (baclofen)-stimulated levels. Overall, the data indicate that aging selectively modulates the activity of Gαq/₁₁ within the hippocampus leading to deficient modulation of [Ca(2+)]i following stimulation of mAChRs but these changes are not related to spatial learning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Detection the changes of hippocampal volume and the lateral ventricle vein in the patients with depression with susceptibility weighted imaging and morphological measurement

    International Nuclear Information System (INIS)

    Song Huihui; Li Yuefeng; Wang Dongqing; Wei Chuanshe; Duan Ruigen; Zhao Tian; Zhao Liang; Jiang Ping

    2013-01-01

    Objective: To study the hippocampal structure in the patients with depression in varying degrees of severity with the combination of the susceptibility weighted imaging (SWI) and morphological measurement. Methods: Sixty patients (divided equally into mild, moderate and major group as the conditions of the severity of depression) and 20 healthy controls were scanned using the three dimensional fast low angle shot imaging sequence (3D-FLASH) and SWI. Then the morphological images were manually segmented and delineated by three doctors. The hippocampal volumes were calculated and standardized. The maximum diameter, length and the branching numbers of the Inferior ventricular vein which were clear demonstrated in the SWI were measured. The changes in the venous system and morphology among the three different degrees of severity in depression and the healthy controls were contrastively analyzed by the one-way analysis of variance. Results: Left and right hippocampal volumes: the mild group were 2246 ± 147, 2271 ± 151; the moderate group were 2028 ± 65, 2038 ± 57; the major group were 1965 ± 129, 1962 ± 110; the healthy control were 2287 ± 160, 2305 ± 171. There were statistically significant differences among the four groups (F = 7.45, 8.55, P < 0.01). The hippocampal volumes of depressive patients were smaller than that of the healthy controls, with the biggest variability occurred in the major depressive patients (Dunnett-t = -7.04, -7.54, P < 0.01) and the second in the moderate group (Dunnett-t = -6.73, -6.64, P < 0.01). There were no statistical significant difference between the mild group and the control (Dunnett-t = -0.85, -0.67, P > 0.05). The diameter,length and branch numbers of the lateral ventricle vein: the mild group were (0.94 ± 0.09) mm, (12.0 ± 1.07) mm and 3.67 ± 1.03 ; the moderate group were (0.81 ± 0.04) mm, (10.2 ± 1.25) mm and 2.00 ± 0.89 ; the major group were (0.70 ± 0.08) mm, (8.6 ± 1.40) mm and 1.83 ± 0.75 ; the healthy

  4. Subregional Hippocampal Morphology and Psychiatric Outcome in Adolescents Who Were Born Very Preterm and at Term.

    Directory of Open Access Journals (Sweden)

    James H Cole

    Full Text Available The hippocampus has been reported to be structurally and functionally altered as a sequel of very preterm birth (<33 weeks gestation, possibly due its vulnerability to hypoxic-ischemic damage in the neonatal period. We examined hippocampal volumes and subregional morphology in very preterm born individuals in mid- and late adolescence and their association with psychiatric outcome.Structural brain magnetic resonance images were acquired at two time points (baseline and follow-up from 65 ex-preterm adolescents (mean age = 15.5 and 19.6 years and 36 term-born controls (mean age=15.0 and 19.0 years. Hippocampal volumes and subregional morphometric differences were measured from manual tracings and with three-dimensional shape analysis. Psychiatric outcome was assessed with the Rutter Parents' Scale at baseline, the General Health Questionnaire at follow-up and the Peters Delusional Inventory at both time points.In contrast to previous studies we did not find significant difference in the cross-sectional or longitudinal hippocampal volumes between individuals born preterm and controls, despite preterm individual having significantly smaller whole brain volumes. Shape analysis at baseline revealed subregional deformations in 28% of total bilateral hippocampal surface, reflecting atrophy, in ex-preterm individuals compared to controls, and in 22% at follow-up. In ex-preterm individuals, longitudinal changes in hippocampal shape accounted for 11% of the total surface, while in controls they reached 20%. In the whole sample (both groups larger right hippocampal volume and bilateral anterior surface deformations at baseline were associated with delusional ideation scores at follow-up.This study suggests a dynamic association between cross-sectional hippocampal volumes, longitudinal changes and surface deformations and psychosis proneness.

  5. Effects of aerobic exercise on cognition and hippocampal volume in Alzheimer's disease: study protocol of a randomized controlled trial (The FIT-AD trial).

    Science.gov (United States)

    Yu, Fang; Bronas, Ulf G; Konety, Suma; Nelson, Nathaniel W; Dysken, Maurice; Jack, Clifford; Wyman, Jean F; Vock, David; Smith, Glenn

    2014-10-11

    Alzheimer's disease, a global public health issue, accounts for 60 to 80% of all dementias. Alzheimer's disease primarily causes cognitive impairment and drugs have only modest short-term effects, highlighting a pressing need to develop effective interventions. Aerobic exercise holds promise for treating cognitive impairment in Alzheimer's disease through biologically sound mechanisms. Nonetheless, aerobic exercise studies in Alzheimer's disease are limited with mixed findings. This pilot randomized controlled trial will investigate the effects of a 6-month, individualized, moderate-intensity cycling intervention (20 to 50 minutes per session, 3 times a week) on cognition and hippocampal volume in community-dwelling older adults with mild-to-moderate Alzheimer's disease. The specific aims are to: 1) determine the immediate effect of the cycling intervention on cognition in Alzheimer's disease; 2) examine if the cycling intervention slows cognitive decline in Alzheimer's disease from baseline to 12 months; and 3) assess the effect of aerobic exercise on hippocampal volume over 12 months. Ninety subjects will be randomized on a 2:1 allocation ratio to cycling or attention control (low-intensity stretching) and followed for another 6 months. Allocations will be concealed to all investigators and outcome assessors will be blinded to group assignments and previous data. Cognition will be measured by the Alzheimer's disease Assessment Scale-Cognition at baseline before randomization and at 3, 6, 9, and 12 months. Hippocampal volume will be measured by magnetic resonance imaging at baseline and 6 and 12 months. The sample size of 90 will give 80% power to detect a 2.5-point difference in within-group changes in the Alzheimer's disease Assessment Scale-Cognition at 6 months for the cycling group. Findings from this study will address the critical gap of exercise efficacy in Alzheimer's disease and use of magnetic resonance imaging as an outcome measure in clinical trials

  6. Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case-control study in long-term survivors from cancer in the head and neck region.

    Science.gov (United States)

    Olsson, Erik; Eckerström, Carl; Berg, Gertrud; Borga, Magnus; Ekholm, Sven; Johannsson, Gudmundur; Ribbelin, Susanne; Starck, Göran; Wysocka, Anna; Löfdahl, Elisabet; Malmgren, Helge

    2012-11-29

    An earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients' lowered QoL was coupled to a reduction in hippocampal volume. Patients (11 men and 4 women, age 31-65) treated for head and neck cancer 4-10 years earlier and with no sign of recurrence or pituitary dysfunction, and 15 matched controls were included. The estimated radiation doses to the basal brain including the hippocampus (1.5 - 9.3 Gy) had been calculated in the earlier study. The hippocampal volumetry was done on coronal sections from a 1.5 T MRI scanner. Measurements were done by two independent raters, blinded to patients and controls, using a custom method for computer assisted manual segmentation. The volumes were normalized for intracranial volume which was also measured manually. The paired t test and Wilcoxon's signed rank test were used for the main statistical analysis. There was no significant difference with respect to left, right or total hippocampal volume between patients and controls. All mean differences were close to zero, and the two-tailed 95% confidence interval for the difference in total, normalized volume does not include a larger than 8% deficit in the patients. The study gives solid evidence against the hypothesis that the patients' lowered quality of life was due to a major reduction of hippocampal volume.

  7. Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case–control study in long-term survivors from cancer in the head and neck region

    Science.gov (United States)

    2012-01-01

    Background An earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients’ lowered QoL was coupled to a reduction in hippocampal volume. Methods Patients (11 men and 4 women, age 31–65) treated for head and neck cancer 4–10 years earlier and with no sign of recurrence or pituitary dysfunction, and 15 matched controls were included. The estimated radiation doses to the basal brain including the hippocampus (1.5 – 9.3 Gy) had been calculated in the earlier study. The hippocampal volumetry was done on coronal sections from a 1.5 T MRI scanner. Measurements were done by two independent raters, blinded to patients and controls, using a custom method for computer assisted manual segmentation. The volumes were normalized for intracranial volume which was also measured manually. The paired t test and Wilcoxon’s signed rank test were used for the main statistical analysis. Results There was no significant difference with respect to left, right or total hippocampal volume between patients and controls. All mean differences were close to zero, and the two-tailed 95% confidence interval for the difference in total, normalized volume does not include a larger than 8% deficit in the patients. Conclusion The study gives solid evidence against the hypothesis that the patients’ lowered quality of life was due to a major reduction of hippocampal volume. PMID:23193977

  8. A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

    DEFF Research Database (Denmark)

    Stomby, Andreas; Otten, Julia; Ryberg, Mats

    2017-01-01

    Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized...... to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group...... of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing...

  9. Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis.

    Science.gov (United States)

    Ebrahimzadeh Bideskan, Alireza; Mohammadipour, Abbas; Fazel, Alireza; Haghir, Hossein; Rafatpanah, Houshang; Hosseini, Mahmoud; Rajabzadeh, Aliakbar

    2017-07-05

    The usage of Titanium dioxide nanoparticles (TiO 2 -NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO 2 -NPs during developmental period has been associated with hippocampal injury and with a decrease in learning and memory status of the offspring. However, little is known about its injury mechanism. This paper describes the in vivo neurotoxic effects of TiO 2 -NPs on rat offspring hippocampus during developmental period. Pregnant and lactating Wistar rats received intragastric TiO 2 -NPs (100mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21 and postnatal day (PD) 2 to (PD) 21 respectively. Animals in the control groups received an equal volume of distilled water via gavage. At the end of the treatment process, offspring were deeply anesthetized and sacrificed. Then brains of each group were collected and sections of the rat offspring's brains were stained using TUNEL staining (for detection of apoptotic cells) and immunostaining (for neurogenesis). Moreover, the right hippocampus (n=6 per each group) were removed from the right hemisphere for evaluating the expression of Bax and Bcl-2 level. Results of histopatological examination by TUNEL staining showed that maternal exposure to TiO 2 -NPs during pregnancy and lactation periods increased apoptotic cells significantly (P<0.01) in the offspring hippocampus. The immunolabeling of double cortin (DCX) protein as neurogenesis marker also showed that TiO 2 -NPs reduced neurogenesis in the hippocampus of the offspring (P<0.05). Moreover, in comparison with the control group, the mRNA levels of Bax and Bcl-2 in the TiO 2 -NPs group significantly increased and decreased, respectively (P<0.01). These findings provide strong evidence that maternal exposure to TiO 2 -NPs significantly impact hippocampal neurogenesis and apoptosis in the offspring. The potential impact of nanoparticle exposure for millions of pregnant mothers and

  10. Volume regulated anion channel currents of rat hippocampal neurons and their contribution to oxygen-and-glucose deprivation induced neuronal death.

    Directory of Open Access Journals (Sweden)

    Huaqiu Zhang

    2011-02-01

    Full Text Available Volume-regulated anion channels (VRAC are widely expressed chloride channels that are critical for the cell volume regulation. In the mammalian central nervous system, the physiological expression of neuronal VRAC and its role in cerebral ischemia are issues largely unknown. We show that hypoosmotic medium induce an outwardly rectifying chloride conductance in CA1 pyramidal neurons in rat hippocampal slices. The induced chloride conductance was sensitive to some of the VRAC inhibitors, namely, IAA-94 (300 µM and NPPB (100 µM, but not to tamoxifen (10 µM. Using oxygen-and-glucose deprivation (OGD to simulate ischemic conditions in slices, VRAC activation appeared after OGD induced anoxic depolarization (AD that showed a progressive increase in current amplitude over the period of post-OGD reperfusion. The OGD induced VRAC currents were significantly inhibited by inhibitors for glutamate AMPA (30 µM NBQX and NMDA (40 µM AP-5 receptors in the OGD solution, supporting the view that induction of AD requires an excessive Na(+-loading via these receptors that in turn to activate neuronal VRAC. In the presence of NPPB and DCPIB in the post-OGD reperfusion solution, the OGD induced CA1 pyramidal neuron death, as measured by TO-PRO-3-I staining, was significantly reduced, although DCPIB did not appear to be an effective neuronal VRAC blocker. Altogether, we show that rat hippocampal pyramidal neurons express functional VRAC, and ischemic conditions can initial neuronal VRAC activation that may contribute to ischemic neuronal damage.

  11. Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

    Science.gov (United States)

    Kalyan-Masih, Priya; Vega-Torres, Julio David; Haddad, Elizabeth; Rainsbury, Sabrina; Baghchechi, Mohsen

    2016-01-01

    Abstract Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders. PMID:27844058

  12. Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes.

    Science.gov (United States)

    Kalyan-Masih, Priya; Vega-Torres, Julio David; Miles, Christina; Haddad, Elizabeth; Rainsbury, Sabrina; Baghchechi, Mohsen; Obenaus, Andre; Figueroa, Johnny D

    2016-01-01

    Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress ( p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders.

  13. Intrinsic cellular and molecular properties of in vivo hippocampal synaptic plasticity are altered in the absence of key synaptic matrix molecules.

    Science.gov (United States)

    Jansen, Stephan; Gottschling, Christine; Faissner, Andreas; Manahan-Vaughan, Denise

    2017-08-01

    Hippocampal synaptic plasticity comprises a key cellular mechanism for information storage. In the hippocampus, both long-term potentiation (LTP) and long-term depression (LTD) are triggered by synaptic Ca 2+ -elevations that are typically mediated by the opening of voltage-gated cation channels, such as N-methyl-d-aspartate receptors (NMDAR), in the postsynaptic density. The integrity of the post-synaptic density is ensured by the extracellular matrix (ECM). Here, we explored whether synaptic plasticity is affected in adult behaving mice that lack the ECM proteins brevican, neurocan, tenascin-C, and tenascin-R (KO). We observed that the profiles of synaptic potentiation and depression in the dentate gyrus (DG) were profoundly altered compared to plasticity profiles in wild-type littermates (WT). Specifically, synaptic depression was amplified in a frequency-dependent manner and although late-LTP (>24 hr) was expressed following strong afferent tetanization, the early component of LTP (4 hr) elicited by weaker tetanization was equivalent in WT and KO animals. Furthermore, this latter form of LTP was NMDAR-dependent in WT but not KO mice. Scrutiny of DG receptor expression revealed significantly lower levels of both the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor, of the metabotropic glutamate receptor, mGlu5 and of the L-type calcium channel, Ca v 1.3 in KO compared to WT animals. Homer 1a and of the P/Q-type calcium channel, Ca v 1.2 were unchanged in KO mice. Taken together, findings suggest that in mice that lack multiple ECM proteins, synaptic plasticity is intact, but is fundamentally different. © 2017 Wiley Periodicals, Inc.

  14. A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes.

    Science.gov (United States)

    Stomby, Andreas; Otten, Julia; Ryberg, Mats; Nyberg, Lars; Olsson, Tommy; Boraxbekk, Carl-Johan

    2017-01-01

    Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference ( n = 6). The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798.

  15. Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia.

    Science.gov (United States)

    Logue, Mark W; van Rooij, Sanne J H; Dennis, Emily L; Davis, Sarah L; Hayes, Jasmeet P; Stevens, Jennifer S; Densmore, Maria; Haswell, Courtney C; Ipser, Jonathan; Koch, Saskia B J; Korgaonkar, Mayuresh; Lebois, Lauren A M; Peverill, Matthew; Baker, Justin T; Boedhoe, Premika S W; Frijling, Jessie L; Gruber, Staci A; Harpaz-Rotem, Ilan; Jahanshad, Neda; Koopowitz, Sheri; Levy, Ifat; Nawijn, Laura; O'Connor, Lauren; Olff, Miranda; Salat, David H; Sheridan, Margaret A; Spielberg, Jeffrey M; van Zuiden, Mirjam; Winternitz, Sherry R; Wolff, Jonathan D; Wolf, Erika J; Wang, Xin; Wrocklage, Kristen; Abdallah, Chadi G; Bryant, Richard A; Geuze, Elbert; Jovanovic, Tanja; Kaufman, Milissa L; King, Anthony P; Krystal, John H; Lagopoulos, Jim; Bennett, Maxwell; Lanius, Ruth; Liberzon, Israel; McGlinchey, Regina E; McLaughlin, Katie A; Milberg, William P; Miller, Mark W; Ressler, Kerry J; Veltman, Dick J; Stein, Dan J; Thomaes, Kathleen; Thompson, Paul M; Morey, Rajendra A

    2018-02-01

    Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma. Published by Elsevier Inc.

  16. A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Andreas Stomby

    2017-12-01

    Full Text Available Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12 with and without high intensity exercise (PDEX, n = 12 for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference (n = 6. The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798.

  17. Effects of ApoE-epsilon4 allele load and age on the rates of grey matter and hippocampal volumes loss in a longitudinal cohort of 1186 healthy elderly persons.

    Science.gov (United States)

    Crivello, Fabrice; Lemaître, Hervé; Dufouil, Carole; Grassiot, Blandine; Delcroix, Nicolas; Tzourio-Mazoyer, Nathalie; Tzourio, Christophe; Mazoyer, Bernard

    2010-11-15

    In a sample of 1186 healthy subjects aged 65 to 89 years who were scanned twice with MRI 3.6 years apart, we studied the effects of age and ApoE-epsilon4 allele load on the rate of atrophy of grey matter and hippocampus. Rates of grey matter and hippocampal volumes loss were computed from T1-weighted magnetic resonance images using voxel-based morphometry and region of interest analysis. Longitudinal analysis showed that an age-related annual rate of grey matter volume loss was only seen in epsilon4 homozygotes only (n=14) whereas no age effect was seen epsilon4 heterozygotes (n=239) and in noncarriers (n=933). ApoE-epsilon4 homozygotes also had a significantly larger rate of hippocampal volume loss than heterozygotes or noncarriers. During the same period, no effect or interaction of ApoE genotype and age was observed on cognitive decline, as assessed by the Mini Mental State Examination (MMSE). These data do not suggest an epsilon4 gene dose effect on the rate of hippocampal volume loss in healthy elderly subjects as most of the effect was limited to homozygotes. Hippocampal volume loss may not be a good imaging marker to understand the effect of the ApoE-epsilon4 allele on the risk of dementia in a population-based setting. It could be hypothesized that the impact of a single ApoE-epsilon4 allele on brain structures is largely delayed in time. Copyright 2010 Elsevier Inc. All rights reserved.

  18. The origin and history of alteration and carbonatization of the Yucca Mountain ignimbrites. Volume I

    International Nuclear Information System (INIS)

    Szymanski, J.S.

    1992-04-01

    This document contains Volume I of the report entitled The Origin and History of Alteration and Carbonatization of the Yucca Mountain Ignimbrites by Jerry S. Szymanski and a related correspondence with comments by Donald E. Livingston. In the Great Basin, the flow of terrestrial heat through the crust is affected in part by the flow of fluids. At Yucca Mountain, the role of fluids in crustal heat transport is manifested at the surface by youthful calcretes, sinters, bedrock veins, hydrothermal eruption breccias and hydrothermal alteration. This report discusses evidence for recent metasomatism high in the stratigraphic section at Yucca Mountain. Over the last several hundred years, episodes of calcite emplacement contemporaneous with local mafic volcanism have occurred at intervals that are not long in comparison with the isolation time required for a High-Level Radioactive Waste repository

  19. The origin and history of alteration and carbonatization of the Yucca Mountain ignimbrites. Volume I

    Energy Technology Data Exchange (ETDEWEB)

    Szymanski, J.S.

    1992-04-01

    This document contains Volume I of the report entitled The Origin and History of Alteration and Carbonatization of the Yucca Mountain Ignimbrites by Jerry S. Szymanski and a related correspondence with comments by Donald E. Livingston. In the Great Basin, the flow of terrestrial heat through the crust is affected in part by the flow of fluids. At Yucca Mountain, the role of fluids in crustal heat transport is manifested at the surface by youthful calcretes, sinters, bedrock veins, hydrothermal eruption breccias and hydrothermal alteration. This report discusses evidence for recent metasomatism high in the stratigraphic section at Yucca Mountain. Over the last several hundred years, episodes of calcite emplacement contemporaneous with local mafic volcanism have occurred at intervals that are not long in comparison with the isolation time required for a High-Level Radioactive Waste repository.

  20. Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

    Science.gov (United States)

    Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

    2011-03-01

    Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

  1. The hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety.

    Science.gov (United States)

    Scott, Julia A; Goodrich-Hunsaker, Naomi; Kalish, Kristopher; Lee, Aaron; Hunsaker, Michael R; Schumann, Cynthia M; Carmichael, Owen T; Simon, Tony J

    2016-04-01

    Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an elevated risk for schizophrenia, which increases with history of childhood anxiety. Altered hippocampal morphology is a common neuroanatomical feature of 22q11.2DS and idiopathic schizophrenia. Relating hippocampal structure in children with 22q11.2DS to anxiety and impaired cognitive ability could lead to hippocampus-based characterization of psychosis-proneness in this at-risk population. We measured hippocampal volume using a semiautomated approach on MRIs collected from typically developing children and children with 22q11.2DS. We then analyzed hippocampal morphology with Localized Components Analysis. We tested the modulating roles of diagnostic group, hippocampal volume, sex and age on local hippocampal shape components. Lastly, volume and shape components were tested as covariates of IQ and anxiety. We included 48 typically developing children and 69 children with 22q11.2DS in our study. Hippocampal volume was reduced bilaterally in children with 22q11.2DS, and these children showed greater variation in the shape of the anterior hippocampus than typically developing children. Children with 22q11.2DS had greater inward deformation of the anterior hippocampus than typically developing children. Greater inward deformation of the anterior hippocampus was associated with greater severity of anxiety, specifically fear of physical injury, within the 22q11.2DS group. Shape alterations are not specific to hippocampal subfields. Alterations in the structure of the anterior hippocampus likely affect function and may impact limbic circuitry. We suggest these alterations potentially contribute to anxiety symptoms in individuals with 22q11.2DS through modulatory pathways. Altered hippocampal morphology may be uniquely linked to anxiety risk factors for schizophrenia, which could be a powerful neuroanatomical marker of schizophrenia risk and hence protection.

  2. History of mild traumatic brain injury is associated with deficits in relational memory, reduced hippocampal volume, and less neural activity later in life

    Directory of Open Access Journals (Sweden)

    Jim M Monti

    2013-08-01

    Full Text Available Evidence suggests that a history of head trauma is associated with memory deficits later in life. The majority of previous research has focused on moderate-to-severe traumatic brain injury (TBI, but recent evidence suggests that even a mild TBI (mTBI can interact with the aging process and produce reductions in memory performance. This study examined the association of mTBI with memory and the brain by comparing young and middle-aged adults who have had mTBI in their recent (several years ago and remote (several decades ago past, respectively, with control subjects on a face-scene relational memory paradigm while they underwent functional magnetic resonance imaging. Hippocampal volumes were also examined from high-resolution structural images. Results indicated middle-aged adults with a head injury in their remote past had impaired memory compared to gender, age, and education matched control participants, consistent with previous results in the study of memory, aging, and TBI. The present findings extended previous results by demonstrating that these individuals also had smaller bilateral hippocampi, and had reduced neural activity during memory performance in cortical regions important for memory retrieval. These results indicate that a history of mTBI may be one of the many factors that negatively influence cognitive and brain health in aging.

  3. Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings.

    Science.gov (United States)

    Greven, Corina U; Bralten, Janita; Mennes, Maarten; O'Dwyer, Laurence; van Hulzen, Kimm J E; Rommelse, Nanda; Schweren, Lizanne J S; Hoekstra, Pieter J; Hartman, Catharina A; Heslenfeld, Dirk; Oosterlaan, Jaap; Faraone, Stephen V; Franke, Barbara; Zwiers, Marcel P; Arias-Vasquez, Alejandro; Buitelaar, Jan K

    2015-05-01

    Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder. It has been linked to reductions in total brain volume and subcortical abnormalities. However, owing to heterogeneity within and between studies and limited sample sizes, findings on the neuroanatomical substrates of ADHD have shown considerable variability. Moreover, it remains unclear whether neuroanatomical alterations linked to ADHD are also present in the unaffected siblings of those with ADHD. To examine whether ADHD is linked to alterations in whole-brain and subcortical volumes and to study familial underpinnings of brain volumetric alterations in ADHD. In this cross-sectional study, we included participants from the large and carefully phenotyped Dutch NeuroIMAGE sample (collected from September 2009-December 2012) consisting of 307 participants with ADHD, 169 of their unaffected siblings, and 196 typically developing control individuals (mean age, 17.21 years; age range, 8-30 years). Whole-brain volumes (total brain and gray and white matter volumes) and volumes of subcortical regions (nucleus accumbens, amygdala, caudate nucleus, globus pallidus, hippocampus, putamen, thalamus, and brainstem) were derived from structural magnetic resonance imaging scans using automated tissue segmentation. Regression analyses revealed that relative to control individuals, participants with ADHD had a 2.5% smaller total brain (β = -31.92; 95% CI, -52.69 to -11.16; P = .0027) and a 3% smaller total gray matter volume (β = -22.51; 95% CI, -35.07 to -9.96; P = .0005), while total white matter volume was unaltered (β = -10.10; 95% CI, -20.73 to 0.53; P = .06). Unaffected siblings had total brain and total gray matter volumes intermediate to participants with ADHD and control individuals. Significant age-by-diagnosis interactions showed that older age was linked to smaller caudate (P brain volume) in control individuals, whereas age was unrelated to these volumes in

  4. MK-801 (Dizocilpine) Regulates Multiple Steps of Adult Hippocampal Neurogenesis and Alters Psychological Symptoms via Wnt/β-Catenin Signaling in Parkinsonian Rats.

    Science.gov (United States)

    Singh, Sonu; Mishra, Akanksha; Srivastava, Neha; Shukla, Shubha

    2017-03-15

    Adult hippocampal neurogenesis is directly involved in regulation of stress, anxiety, and depression that are commonly observed nonmotor symptoms in Parkinson's disease (PD). These symptoms do not respond to pharmacological dopamine replacement therapy. Excitotoxic damage to neuronal cells by N-methyl-d-aspartate (NMDA) receptor activation is also a major contributing factor in PD development, but whether it regulates hippocampal neurogenesis and nonmotor symptoms in PD is yet unexplored. Herein, for the first time, we studied the effect of MK-801, an NMDA receptor antagonist, on adult hippocampal neurogenesis and behavioral functions in 6-OHDA (6-hydroxydopamine) induced rat model of PD. MK-801 treatment (0.2 mg/kg, ip) increased neural stem cell (NSC) proliferation, self-renewal capacity, long-term survival, and neuronal differentiation in the hippocampus of rat model of PD. MK-801 potentially enhanced long-term survival, improved dendritic arborization of immature neurons, and reduced 6-OHDA induced neurodegeneration via maintaining the NSC pool in hippocampus, leading to decreased anxiety and depression-like phenotypes in the PD model. MK-801 inhibited glycogen synthase kinase-3β (GSK-3β) through up-regulation of Wnt-3a, which resulted in the activation of Wnt/β-catenin signaling leading to enhanced hippocampal neurogenesis in PD model. Additionally, MK-801 treatment protected the dopaminergic (DAergic) neurons in the nigrostriatal pathway and improved motor functions by increasing the expression of Nurr-1 and Pitx-3 in the PD model. Therefore, MK-801 treatment serves as a valuable tool to enhance hippocampal neurogenesis in PD, but further studies are needed to revisit the role of MK-801 in the neurodegenerative disorder before proposing a potential therapeutic candidate.

  5. White matter disruption at the prodromal stage of Alzheimer's disease: Relationships with hippocampal atrophy and episodic memory performance

    Directory of Open Access Journals (Sweden)

    Florence Rémy

    2015-01-01

    Full Text Available White matter tract alterations have been consistently described in Alzheimer's disease (AD. In particular, limbic fronto-temporal connections, which are critical to episodic memory function, may degenerate early in the course of the disease. However the relation between white matter tract degeneration, hippocampal atrophy and episodic memory impairment at the earliest stages of AD is still unclear. In this magnetic resonance imaging study, white matter integrity and hippocampal volumes were evaluated in patients with amnestic mild cognitive impairment due to AD (Albert et al., 2011 (n = 22 and healthy controls (n = 15. Performance in various episodic memory tasks was also evaluated in each participant. Relative to controls, patients showed a significant reduction of white matter fractional anisotropy (FA and increase of radial diffusivity (RD in the bilateral uncinate fasciculus, parahippocampal cingulum and fornix. Within the patient group, significant intra-hemispheric correlations were notably found between hippocampal grey matter volume and FA in the uncinate fasciculus, suggesting a relationship between atrophy and disconnection of the hippocampus. Moreover, episodic recognition scores were related with uncinate fasciculus FA across patients. These results indicate that fronto-hippocampal connectivity is reduced from the earliest pre-demential stages of AD. Disruption of fronto-hippocampal connections may occur progressively, in parallel with hippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory.

  6. Cisapride does not alter gastric volume or pH in patients undergoing ambulatory surgery.

    LENUS (Irish Health Repository)

    Lydon, A

    2012-02-03

    PURPOSE: To evaluate the efficacy of 20 mg cisapride p.o. in reducing residual gastric volume and pH in adult ambulatory surgical patients. METHODS: Using a prospective randomised double-blind controlled design, we administered either 20 mg cisapride p.o. or placebo preoperatively to 64 ASA 1-2 ambulatory surgical patients. Following induction of anesthesia we measured volume and pH of residual gastric contents, using blind aspiration through an orogastric tube. Parametric data were analysed using unpaired, one tail Students\\' t test. Non-parametric data were analysed using Fishers Exact test and Chi square analysis. Statistical significance was accepted at the probability level of < 0.05. RESULTS: Residual gastric volumes were similar in the two groups (19.5 +\\/- 23.8, 23.9 +\\/- 24.4 ml), in the cisapride and placebo groups respectively, P=0.24). Data shown are mean (+\\/- SD). The proportions of patients with a residual gastric volume exceeding 0.4 ml x kg(-1) were similar in the two groups (4 of 28, and 8 of 23 patients in the cisapride and placebo groups respectively, P=0.09). The pH of the residual gastric contents were similar in the cisapride and placebo groups (1.6 +\\/- 0.5, 1.4 +\\/- 0.5, respectively, P=0.26). The proportions of patients with pH < 2.5 was also similar in the cisapride and placebo groups (21 of 25, and 20 of 21 patients respectively, P=0.2). CONCLUSIONS: Preoperative administration of 20 mg cisapride p.o. to patients scheduled for outpatient surgery does not alter either the volume or the pH of gastric contents. Its use in this setting is of no apparent clinical benefit.

  7. Effect of partial volume correction on muscarinic cholinergic receptor imaging with single-photon emission tomography in patients with temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Weckesser, M.; Ziemons, K.; Griessmeier, M.; Sonnenberg, F.; Langen, K.J.; Mueller-Gaertner, H.W.; Hufnagel, A.; Elger, C.E.; Hacklaender, T.; Holschbach, M.

    1997-01-01

    Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [ 123 I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration. (orig.). With 2 figs., 2 tabs

  8. The alteration of gray matter volume and cognitive control in adolescents with internet gaming disorder

    Directory of Open Access Journals (Sweden)

    Hongmei eWang

    2015-03-01

    Full Text Available Objective: Internet gaming disorder (IGD has been investigated by many behavioral and neuroimaging studies, for it has became one of the main behavior disorders among adolescents. However, few studies focused on the relationship between alteration of gray matter volume (GMV and cognitive control feature in IGD adolescents. Methods: Twenty-eight participants with IAD and twenty-eight healthy age and gender matched controls participated in the study. Brain morphology of adolescents with IGD and healthy controls was investigated using an optimized voxel-based morphometry (VBM technique. Cognitive control performances were measured by Stroop task, and correlation analysis was performed between brain structural change and behavioral performance in IGD group. Results: The results showed that GMV of the bilateral anterior cingulate cortex (ACC, precuneus, supplementary motor area (SMA, superior parietal cortex, left dorsal lateral prefrontal cortex (DLPFC, left insula, and bilateral cerebellum decreased in the IGD participants compared with healthy controls. Moreover, GMV of the ACC was negatively correlated with the incongruent response errors of Stroop task in IGD group. Conclusion: Our results suggest that the alteration of GMV is associated with the performance change of cognitive control in adolescents with IGD, which indicating substantial brain image effects induced by IGD.

  9. Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats.

    Science.gov (United States)

    Blanco, Eduardo; Galeano, Pablo; Holubiec, Mariana I; Romero, Juan I; Logica, Tamara; Rivera, Patricia; Pavón, Francisco J; Suarez, Juan; Capani, Francisco; Rodríguez de Fonseca, Fernando

    2015-01-01

    Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA.

  10. Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats

    Science.gov (United States)

    Blanco, Eduardo; Galeano, Pablo; Holubiec, Mariana I.; Romero, Juan I.; Logica, Tamara; Rivera, Patricia; Pavón, Francisco J.; Suarez, Juan; Capani, Francisco; Rodríguez de Fonseca, Fernando

    2015-01-01

    Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA. PMID:26578900

  11. DEVELOPMENTAL HYPOTHYROIDISM IMPAIRS HIPPOCAMPAL LEARNING AND SYNAPTIC TRANSMISSION IN VIVO.

    Science.gov (United States)

    A number of environmental chemicals have been reported to alter thyroid hormone (TH) function. It is well established that severe hypothyroidism during critical periods of brain development leads to alterations in hippocampal structure and learning deficits, yet evaluation of ...

  12. The Alterations of IL-1Beta, IL-6, and TGF-Beta Levels in Hippocampal CA3 Region of Chronic Restraint Stress Rats after Electroacupuncture (EA Pretreatment

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    Tianwei Guo

    2014-01-01

    Full Text Available Immunological reactions induced by proinflammatory cytokines have been involved in the pathogenesis of depressive disorders. Recent studies showed that Electroacupuncture (EA was able to reduce depressive symptoms; however, the underlying mechanism and its potential targets remain unknown. In the present study, we used a 21-day chronic restraint stress rats as a model to investigate how EA could alleviate depression. Open field test was carried out to evaluate the depressive symptoms at selected time points. At the end of study, immunohistochemistry (IHC was performed to detect the expressions of IL-1beta, IL-6, and TGF-beta in hippocampal CA3 region. We found that chronic restraint stress significantly decreased behavioral activities, whereas EA stimulation at points Baihui (GV 20 and Yintang (GV 29 showed protective effect during the test period. In addition, the IL-1beta, IL-6, and TGF-beta increased in rats exposed to chronic restraint stress, while EA downregulated the levels of IL-1beta and IL-6. These findings implied that EA pretreatment could alleviate depression through modulating IL-1beta and IL-6 expression levels in hippocampal CA3 region.

  13. In a Canine Pneumonia Model of Exchange-Transfusion, Altering the Age but Not the Volume of Older Red Blood Cells Markedly Alters Outcome

    Science.gov (United States)

    Cortés-Puch, Irene; Remy, Kenneth E.; Solomon, Steven B.; Sun, Junfeng; Wang, Dong; Al-Hamad, Mariam; Kelly, Seth M.; Sinchar, Derek; Bellavia, Landon; Kanias, Tamir; Popovsky, Mark A.; Kim-Shapiro, Daniel B.; Klein, Harvey G.; Natanson, Charles

    2015-01-01

    Background Massive exchange-transfusion of 42-day-old red blood cells (RBCs) in a canine model of S. aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin bound iron (TBI), non-transferrin bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7-day-old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs. Study Design and Methods Two-year-old purpose-bred infected beagles were transfused with increasing volumes (5-10, 20-40, or 60-80 mL/kg) of either 42- or 7-day-old RBCs (n=36) or 80 mL/kg of either unwashed or washed RBCs with increasing storage age (14, 21, 28, or 35 days) (n=40). Results All volumes transfused (5-80 mL/kg) of 42-day-old RBCs, resulted in alike (i.e., not significantly different) increases in TBI during transfusion as well as in CFH, lung injury, and mortality rates after transfusion. Transfusion of 80 mL/kg of RBCs stored for 14, 21, 28 and 35 days resulted in increased CFH and NTBI in between levels found at 7 and 42 days of storage. However, washing RBCs of intermediate ages (14-35 days) does not alter NTBI and CFH levels or mortality rates. Conclusions Preclinical data suggest that any volume of 42-day-old blood potentially increases risks during established infection. In contrast, even massive volumes of 7-day-old blood result in minimal CFH and NTBI levels and risks. In contrast to the extremes of storage, washing blood stored for intermediate ages does not alter risks of transfusion or NTBI and CFH clearance. PMID:26469998

  14. Subclinical depressive symptoms during late midlife and structural brain alterations

    DEFF Research Database (Denmark)

    Osler, Merete; Sørensen, Lauge; Rozing, Maarten

    2018-01-01

    at age 51, 56, and 59 years, magnetic resonance imaging was performed at age 59. All data processing was performed using the Freesurfer software package except for the texture-scores that were computed using in-house software. Structural brain alterations and associations between depressive symptoms......We explored whether depressive symptoms measured three times during midlife were associated with structural brain alterations quantified using magnetic resonance imaging measurements of volume, cortical thickness, and intensity texture. In 192 men born in 1953 with depressive symptoms measured...... and brain structure outcomes were tested using Pearson's correlation, t test, and linear regression. Depressive symptoms at age 51 showed clear inverse correlations with total gray matter, pallidum, and hippocampal volume with the strongest estimate for hippocampal volume (r = -.22, p 

  15. Regional hippocampal involvement and cognitive impairment in pediatric multiple sclerosis.

    Science.gov (United States)

    Rocca, Maria A; Morelli, Maria E; Amato, Maria P; Moiola, Lucia; Ghezzi, Angelo; Veggiotti, Pierangelo; Capra, Ruggero; Pagani, Elisabetta; Portaccio, Emilio; Fiorino, Agnese; Pippolo, Lorena; Pera, Maria C; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

    2016-04-01

    We assessed global and regional hippocampal volume abnormalities in pediatric multiple sclerosis (MS) patients and their correlations with clinical, neuropsychological and magnetic resonance imaging metrics. From 53 pediatric MS patients and 18 healthy controls, global hippocampal volume was computed using a manual tracing procedure. Regional hippocampal volume modifications were assessed using a radial mapping analysis. MS patients with abnormal performance in three or more tests of a neuropsychological battery for children were classified as cognitively impaired. Global hippocampal volume was reduced in MS patients compared with controls, but did not correlate with clinical, neuropsychological and magnetic resonance imaging measures. Compared to controls, MS patients experienced bilateral radial atrophy of the cornu ammonis, subiculum and dentate gyrus subfields as well as radial hypertrophy of the dentate gyrus subfield. Regional hippocampal volume modifications correlated with brain T2 lesion volume as well as attention and language abilities. Global hippocampal volume did not differ between cognitively impaired (n=12) and cognitively preserved MS patients. Compared to cognitively preserved, cognitively impaired MS patients had atrophy of the subiculum and dentate gyrus subfields of the right hippocampus. Hippocampal subregions have different vulnerability to damage in pediatric MS. Regional rather than global hippocampal involvement contributes to global cognitive impairment as well as to deficits of selected cognitive tests. © The Author(s), 2015.

  16. Early detection of Alzheimer's disease using MRI hippocampal texture

    DEFF Research Database (Denmark)

    Sørensen, Lauge; Igel, Christian; Hansen, Naja Liv

    2016-01-01

    Cognitive impairment in patients with Alzheimer's disease (AD) is associated with reduction in hippocampal volume in magnetic resonance imaging (MRI). However, it is unknown whether hippocampal texture changes in persons with mild cognitive impairment (MCI) that does not have a change...... in hippocampal volume. We tested the hypothesis that hippocampal texture has association to early cognitive loss beyond that of volumetric changes. The texture marker was trained and evaluated using T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and subsequently...

  17. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    NARCIS (Netherlands)

    Papma, Janne M.; Smits, Marion; De Groot, Marius; Mattace-Raso, Francesco U. S.; van der Lugt, Aad; Vrooman, Henri A.; Niessen, W.J.; Koudstaal, Peter J.; van Swieten, John C.; van der Veen, Frederik M.; Prins, Niels D.

    2017-01-01

    Objectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the

  18. Hippocampal network activity is transiently altered by induction of long-term potentiation in the dentate gyrus of freely behaving rats

    Directory of Open Access Journals (Sweden)

    Arthur Bikbaev

    2007-12-01

    Full Text Available A role for oscillatory activity in hippocampal neuronal networks has been proposed in sensory encoding, cognitive functions and synaptic plasticity. In the hippocampus, theta (5–10 Hz and gamma (30–100 Hz oscillations may provide a mechanism for temporal encoding of information, and the basis for formation and retrieval of memory traces. Long-term potentiation (LTP of synaptic transmission, a candidate cellular model of synaptic information storage, is typically induced by high-frequency tetanisation (HFT of afferent pathways. Taking into account the role of oscillatory activity in the processing of information, dynamic changes may occur in hippocampal network activity in the period during HFT and/or soon after it. These changes in rhythmic activity may determine or, at least, contribute to successful potentiation and, in general, to formation of memory. We have found that short-term potentiation (STP and LTP as well LTPfailure are characterised with different profiles of changes in theta and gamma frequencies. Potentiation of synaptic transmission was associated with a significant increase in the relative theta power and mean amplitude of theta cycles in the period encompassing 300 seconds after HFT. Where LTP or STP, but not failure of potentiation, occurred, this facilitation of theta was accompanied by transient increases in gamma power and in the mean amplitude of gamma oscillations within a single theta cycle. Our data support that specific, correlated changes in these parameters are associated with successful synaptic potentiation. These findings suggest that changes in theta-gamma activity associated with induction of LTP may enable synaptic information storage in the hippocampus.

  19. Multimodal assessments of the hippocampal formation in schizophrenia and bipolar disorder: Evidences from neurobehavioral measures and functional and structural MRI

    Directory of Open Access Journals (Sweden)

    Christian Knöchel

    2014-01-01

    Full Text Available A potential clinical and etiological overlap between schizophrenia (SZ and bipolar disorder (BD has long been a subject of discussion. Imaging studies imply functional and structural alterations of the hippocampus in both diseases. Thus, imaging this core memory region could provide insight into the pathophysiology of these disorders and the associated cognitive deficits. To examine possible shared alterations in the hippocampus, we conducted a multi-modal assessment, including functional and structural imaging as well as neurobehavioral measures of memory performance in BD and SZ patients compared with healthy controls. We assessed episodic memory performance, using tests of verbal and visual learning (HVLT, BVMT in three groups of participants: BD patients (n = 21, SZ patients (n = 21 and matched (age, gender, education healthy control subjects (n = 21. In addition, we examined hippocampal resting state functional connectivity, hippocampal volume using voxel-based morphometry (VBM and fibre integrity of hippocampal connections using diffusion tensor imaging (DTI. We found memory deficits, changes in functional connectivity within the hippocampal network as well as volumetric reductions and altered white matter fibre integrity across patient groups in comparison with controls. However, SZ patients when directly compared with BD patients were more severely affected in several of the assessed parameters (verbal learning, left hippocampal volumes, mean diffusivity of bilateral cingulum and right uncinated fasciculus. The results of our study suggest a graded expression of verbal learning deficits accompanied by structural alterations within the hippocampus in BD patients and SZ patients, with SZ patients being more strongly affected. Our findings imply that these two disorders may share some common pathophysiological mechanisms. The results could thus help to further advance and integrate current pathophysiological models of SZ and BD.

  20. Evidence for regional hippocampal damage in patients with schizophrenia

    International Nuclear Information System (INIS)

    Singh, Sadhana; Khushu, Subash; Kumar, Pawan; Goyal, Satnam; Bhatia, Triptish; Deshpande, Smita N.

    2018-01-01

    Schizophrenia patients show cognitive and mood impairments, including memory loss and depression, suggesting damage in the brain regions. The hippocampus is a brain structure that is significantly involved in memory and mood function and shows impairment in schizophrenia. In the present study, we examined the regional hippocampal changes in schizophrenia patients using voxel-based morphometry (VBM), Freesurfer, and proton magnetic resonance spectroscopy ( 1 H MRS) procedures. 1 H MRS and high-resolution T1-weighted magnetic resonance imaging were collected in both healthy control subjects (N = 28) and schizophrenia patients (N = 28) using 3-Tesla whole body MRI system. Regional hippocampal volume was analyzed using VBM and Freesufer procedures. The relative ratios of the neurometabolites were calculated using linear combination model (LCModel). Compared to controls, schizophrenia patients showed significantly decreased gray matter volume in the hippocampus. Schizophrenia patients also showed significantly reduced glutamate (Glu) and myo-inositol (mI) ratios in the hippocampus. Additionally, significant positive correlation between gray matter volume and Glu/tCr was also observed in the hippocampus in schizophrenia. Our findings provide an evidence for a possible association between structural deficits and metabolic alterations in schizophrenia patients. (orig.)

  1. Xenon Reduces Neuronal Hippocampal Damage and Alters the Pattern of Microglial Activation after Experimental Subarachnoid Hemorrhage: A Randomized Controlled Animal Trial

    Directory of Open Access Journals (Sweden)

    Michael Veldeman

    2017-09-01

    observed for the ipsilateral hippocampal regions CA3 and DG, when compared to the control group. In xenon-treated animals, a lower microglial cell count was observed suggesting an immunomodulatory effect generated by xenon. As for now, these results cannot be generalized as only some hippocampal regions are affected. Future studies should assess the time and localization dependency of xenon’s beneficial properties after SAH.

  2. Hippocampal Sclerosis: Causes and Prevention.

    Science.gov (United States)

    Walker, Matthew Charles

    2015-06-01

    Hippocampal sclerosis is the commonest cause of drug-resistant epilepsy in adults, and is associated with alterations to structures and networks beyond the hippocampus.In addition to being a cause of epilepsy, the hippocampus is vulnerable to damage from seizure activity. In particular, prolonged seizures (status epilepticus) can result in hippocampal sclerosis. The hippocampus is also vulnerable to other insults including traumatic brain injury, and inflammation. Hippocampal sclerosis can occur in association with other brain lesions; the prevailing view is that it is probably a secondary consequence. In such instances, successful surgical treatment usually involves the resection of both the lesion and the involved hippocampus. Experimental data have pointed to numerous neuroprotective strategies to prevent hippocampal sclerosis. Initial neuroprotective strategies aimed at glutamate receptors may be effective, but later, metabolic pathways, apoptosis, reactive oxygen species, and inflammation are involved, perhaps necessitating the use of interventions aimed at multiple targets. Some of the therapies that we use to treat status epilepticus may neuroprotect. However, prevention of neuronal death does not necessarily prevent the later development of epilepsy or cognitive deficits. Perhaps, the most important intervention is the early, aggressive treatment of seizure activity, and the prevention of prolonged seizures. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Intermittent fasting promotes prolonged associative interactions during synaptic tagging/capture by altering the metaplastic properties of the CA1 hippocampal neurons.

    Science.gov (United States)

    Dasgupta, Ananya; Kim, Joonki; Manakkadan, Anoop; Arumugam, Thiruma V; Sajikumar, Sreedharan

    2017-12-19

    Metaplasticity is the inherent property of a neuron or neuronal population to undergo activity-dependent changes in neural function that modulate subsequent synaptic plasticity. Here we studied the effect of intermittent fasting (IF) in governing the interactions of associative plasticity mechanisms in the pyramidal neurons of rat hippocampal area CA1. Late long-term potentiation and its associative mechanisms such as synaptic tagging and capture at an interval of 120 min were evaluated in four groups of animals, AL (Ad libitum), IF12 (daily IF for 12 h), IF16 (daily IF for 16 h) and EOD (every other day IF for 24 h). IF had no visible effect on the early or late plasticity but it manifested a critical role in prolonging the associative interactions between weak and strong synapses at an interval of 120 min in IF16 and EOD animals. However, both IF12 and AL did not show associativity at 120 min. Plasticity genes such as Bdnf and Prkcz, which are well known for their expressions in late plasticity and synaptic tagging and capture, were significantly upregulated in IF16 and EOD in comparison to AL. Specific inhibition of brain derived neurotropic factor (BDNF) prevented the prolonged associativity expressed in EOD. Thus, daily IF for 16 h or more can be considered to enhance the metaplastic properties of synapses by improving their associative interactions that might translate into animprovedmemoryformation. Copyright © 2017. Published by Elsevier Inc.

  4. Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats

    Directory of Open Access Journals (Sweden)

    Ga-Young Choi

    2017-01-01

    Full Text Available Curcumin is a major diarylheptanoid component of Curcuma longa with traditional usage for anxiety and depression. It has been known for the anti-inflammatory, antistress, and neurotropic effects. Here we examined curcumin effect in neural plasticity and cell viability. 60-channel multielectrode array was applied on organotypic hippocampal slice cultures (OHSCs to monitor the effect of 10 μM curcumin in long-term depression (LTD through low-frequency stimulation (LFS to the Schaffer collaterals and commissural pathways. Cell viability was assayed by propidium iodide uptake test in OHSCs. In addition, the influence of oral curcumin administration on rat behavior was assessed with the forced swim test (FST. Finally, protein expression levels of brain-derived neurotrophic factor (BDNF and cyclooxygenase-2 (COX-2 were measured by Western blot in chronically stressed rats. Our results demonstrated that 10 μM curcumin attenuated LTD and reduced cell death. It also recovered the behavior immobility of FST, rescued the attenuated BDNF expression, and inhibited the enhancement of COX-2 expression in stressed animals. These findings indicate that curcumin can enhance postsynaptic electrical reactivity and cell viability in intact neural circuits with antidepressant-like effects, possibly through the upregulation of BDNF and reduction of inflammatory factors in the brain.

  5. Alterations in white matter volume and its correlation with clinical characteristics in patients with generalized anxiety disorder

    International Nuclear Information System (INIS)

    Moon, Chung-Man; Jeong, Gwang-Woo

    2015-01-01

    Only a few morphological studies have focused on changes in white matter (WM) volume in patients with generalized anxiety disorder (GAD). We evaluated alterations in WM volume and its correlation with symptom severity and duration of illness in adults with GAD. The 44 subjects were comprised of 22 patients with GAD (13 males and nine females) diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and 22 age-matched healthy controls (13 males and nine females). High-resolution magnetic resonance imaging (MRI) data were processed by voxel-based morphometry (VBM) analysis based on diffeomorphic anatomical registration using the exponentiated Lie algebra (DARTEL) algorithm in SPM8. Patients with GAD showed significantly reduced WM volume, particularly in the dorsolateral prefrontal cortex (DLPFC), anterior limb of the internal capsule (ALIC), and midbrain. In addition, DLPFC volume was negatively correlated with GAD-7 score and illness duration. ALIC volume was negatively correlated with GAD-7 score. Female patients had significantly less orbitofrontal cortex volume compared to that in male patients. The findings demonstrate localized changes in WM volume associated with cognitive and emotional dysfunction in patients with GAD. The finding will be helpful for understanding the neuropathology in patients with GAD. (orig.)

  6. Alterations in white matter volume and its correlation with clinical characteristics in patients with generalized anxiety disorder

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Chung-Man [Chonnam National University Hospital, Research Institute for Medical Imaging, Gwangju (Korea, Republic of); Jeong, Gwang-Woo [Chonnam National University Hospital, Research Institute for Medical Imaging, Gwangju (Korea, Republic of); Chonnam National University Medical School, Department of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2015-11-15

    Only a few morphological studies have focused on changes in white matter (WM) volume in patients with generalized anxiety disorder (GAD). We evaluated alterations in WM volume and its correlation with symptom severity and duration of illness in adults with GAD. The 44 subjects were comprised of 22 patients with GAD (13 males and nine females) diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and 22 age-matched healthy controls (13 males and nine females). High-resolution magnetic resonance imaging (MRI) data were processed by voxel-based morphometry (VBM) analysis based on diffeomorphic anatomical registration using the exponentiated Lie algebra (DARTEL) algorithm in SPM8. Patients with GAD showed significantly reduced WM volume, particularly in the dorsolateral prefrontal cortex (DLPFC), anterior limb of the internal capsule (ALIC), and midbrain. In addition, DLPFC volume was negatively correlated with GAD-7 score and illness duration. ALIC volume was negatively correlated with GAD-7 score. Female patients had significantly less orbitofrontal cortex volume compared to that in male patients. The findings demonstrate localized changes in WM volume associated with cognitive and emotional dysfunction in patients with GAD. The finding will be helpful for understanding the neuropathology in patients with GAD. (orig.)

  7. Update on Hippocampal Sclerosis.

    Science.gov (United States)

    Dutra, Juliana R; Cortés, Etty P; Vonsattel, Jean Paul G

    2015-10-01

    The diagnostic hallmarks of hippocampal sclerosis (HS) are severe volume loss of the hippocampus, severe neuronal loss, and reactive gliosis involving primarily two especially vulnerable fields, CA1 and the subiculum. Occasionally, HS may be the only neuropathological change detected in older individuals with dementia and is known as pure HS. In the majority of cases, HS occurs in the setting of other degenerative changes, usually Alzheimer's disease (AD). In these cases, it is classified as combined HS. Although a clinical profile for HS has been identified, its similarities with AD make the diagnosis during life quite challenging; thus, the diagnosis is often made postmortem. The pathogenesis of HS is not completely understood, but the strong association with transactive response DNA-binding protein 43 (TDP-43), in approximately 90%, and the recent discovery of genetic risk factors are important contributions to a better understanding of the disease process.

  8. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure

    DEFF Research Database (Denmark)

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R

    2015-01-01

    of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally...... late pregnancy results in a stable loss of hippocampal neurons and a progressive reduction of hippocampal volume....

  9. Operationalizing hippocampal volume as an enrichment biomarker for amnestic MCI trials: effect of algorithm, test-retest variability and cut-point on trial cost, duration and sample size

    Science.gov (United States)

    Yu, P.; Sun, J.; Wolz, R.; Stephenson, D.; Brewer, J.; Fox, N.C.; Cole, P.E.; Jack, C.R.; Hill, D.L.G.; Schwarz, A.J.

    2014-01-01

    Objective To evaluate the effect of computational algorithm, measurement variability and cut-point on hippocampal volume (HCV)-based patient selection for clinical trials in mild cognitive impairment (MCI). Methods We used normal control and amnestic MCI subjects from ADNI-1 as normative reference and screening cohorts. We evaluated the enrichment performance of four widely-used hippocampal segmentation algorithms (FreeSurfer, HMAPS, LEAP and NeuroQuant) in terms of two-year changes in MMSE, ADAS-Cog and CDR-SB. We modeled the effect of algorithm, test-retest variability and cut-point on sample size, screen fail rates and trial cost and duration. Results HCV-based patient selection yielded not only reduced sample sizes (by ~40–60%) but also lower trial costs (by ~30–40%) across a wide range of cut-points. Overall, the dependence on the cut-point value was similar for the three clinical instruments considered. Conclusion These results provide a guide to the choice of HCV cut-point for aMCI clinical trials, allowing an informed trade-off between statistical and practical considerations. PMID:24211008

  10. Operationalizing hippocampal volume as an enrichment biomarker for amnestic mild cognitive impairment trials: effect of algorithm, test-retest variability, and cut point on trial cost, duration, and sample size.

    Science.gov (United States)

    Yu, Peng; Sun, Jia; Wolz, Robin; Stephenson, Diane; Brewer, James; Fox, Nick C; Cole, Patricia E; Jack, Clifford R; Hill, Derek L G; Schwarz, Adam J

    2014-04-01

    The objective of this study was to evaluate the effect of computational algorithm, measurement variability, and cut point on hippocampal volume (HCV)-based patient selection for clinical trials in mild cognitive impairment (MCI). We used normal control and amnestic MCI subjects from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) as normative reference and screening cohorts. We evaluated the enrichment performance of 4 widely used hippocampal segmentation algorithms (FreeSurfer, Hippocampus Multi-Atlas Propagation and Segmentation (HMAPS), Learning Embeddings Atlas Propagation (LEAP), and NeuroQuant) in terms of 2-year changes in Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Sum of Boxes (CDR-SB). We modeled the implications for sample size, screen fail rates, and trial cost and duration. HCV based patient selection yielded reduced sample sizes (by ∼40%-60%) and lower trial costs (by ∼30%-40%) across a wide range of cut points. These results provide a guide to the choice of HCV cut point for amnestic MCI clinical trials, allowing an informed tradeoff between statistical and practical considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Intrinsic alterations in the partial molar volume on the protein denaturation: surficial Kirkwood-Buff approach.

    Science.gov (United States)

    Yu, Isseki; Takayanagi, Masayoshi; Nagaoka, Masataka

    2009-03-19

    The partial molar volume (PMV) of the protein chymotrypsin inhibitor 2 (CI2) was calculated by all-atom MD simulation. Denatured CI2 showed almost the same average PMV value as that of native CI2. This is consistent with the phenomenological question of the protein volume paradox. Furthermore, using the surficial Kirkwood-Buff approach, spatial distributions of PMV were analyzed as a function of the distance from the CI2 surface. The profiles of the new R-dependent PMV indicate that, in denatured CI2, the reduction in the solvent electrostatic interaction volume is canceled out mainly by an increment in thermal volume in the vicinity of its surface. In addition, the PMV of the denatured CI2 was found to increase in the region in which the number density of water atoms is minimum. These results provide a direct and detailed picture of the mechanism of the protein volume paradox suggested by Chalikian et al.

  12. Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Monika Burns

    Full Text Available Helicobacter pylori (H.pylori, a bacterial pathogen, is a causative agent of gastritis and peptic ulcer disease and is a strong risk factor for development of gastric cancer. Environmental conditions, such as poor dietary iron resulting in iron deficiency anemia (IDA, enhance H.pylori virulence and increases risk for gastric cancer. IDA affects billions of people worldwide, and there is considerable overlap between regions of high IDA and high H.pylori prevalence. The primary aims of our study were to evaluate the effect of H.pylori infection on behavior, iron metabolism, red blood cell indices, and behavioral outcomes following comorbid H. pylori infection and dietary iron deficiency in a mouse model. C57BL/6 female mice (n = 40 were used; half were placed on a moderately iron deficient (ID diet immediately post-weaning, and the other half were maintained on an iron replete (IR diet. Half were dosed with H.pylori SS1 at 5 weeks of age, and the remaining mice were sham-dosed. There were 4 study groups: a control group (-Hp, IR diet as well as 3 experimental groups (-Hp, ID diet; +Hp, IR diet; +Hp,ID diet. All mice were tested in an open field apparatus at 8 weeks postinfection. Independent of dietary iron status, H.pylori -infected mice performed fewer exploratory behaviors in the open field chamber than uninfected mice (p<0.001. Hippocampal gene expression of myelination markers and dopamine receptor 1 was significantly downregulated in mice on an ID diet (both p<0.05, independent of infection status. At 12 months postinfection, hematocrit (Hct and hemoglobin (Hgb concentration were significantly lower in +Hp, ID diet mice compared to all other study groups. H.pylori infection caused IDA in mice maintained on a marginal iron diet. The mouse model developed in this study is a useful model to study the neurologic, behavioral, and hematologic impact of the common human co-morbidity of H. pylori infection and IDA.

  13. Sleep deprivation and hippocampal vulnerability: changes in neuronal plasticity, neurogenesis and cognitive function.

    Science.gov (United States)

    Kreutzmann, J C; Havekes, R; Abel, T; Meerlo, P

    2015-11-19

    Despite the ongoing fundamental controversy about the physiological function of sleep, there is general consensus that sleep benefits neuronal plasticity, which ultimately supports brain function and cognition. In agreement with this are numerous studies showing that sleep deprivation (SD) results in learning and memory impairments. Interestingly, such impairments appear to occur particularly when these learning and memory processes require the hippocampus, suggesting that this brain region may be particularly sensitive to the consequences of sleep loss. Although the molecular mechanisms underlying sleep and memory formation remain to be investigated, available evidence suggests that SD may impair hippocampal neuronal plasticity and memory processes by attenuating intracellular cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling which may lead to alterations in cAMP response element binding protein (CREB)-mediated gene transcription, neurotrophic signaling, and glutamate receptor expression. When restricted sleep becomes a chronic condition, it causes a reduction of hippocampal cell proliferation and neurogenesis, which may eventually lead to a reduction in hippocampal volume. Ultimately, by impairing hippocampal plasticity and function, chronically restricted and disrupted sleep contributes to cognitive disorders and psychiatric diseases. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Hippocampal "gliosis only" on MR imaging represents a distinct entity in epilepsy patients.

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    Hattingen, Elke; Enkirch, Simon Jonas; Jurcoane, Alina; Kruse, Maximilian; Delev, Daniel; Grote, Alexander; Becker, Albert

    2018-02-01

    The purpose of this study is to evaluate whether patients with drug-resistant mesial temporal lobe epilepsy (TLE) due to hippocampal "gliosis only" have different MRI features than those with hippocampal sclerosis (HS). Most TLE patients have HS corresponding to severe neuronal loss and gliosis, but a few have "gliosis only" without significant reduction of neuronal density. We analyzed the morphology of cerebral 3 T MRIs (T1, T2, and FLAIR) of 103 patients with HS and 20 with "gliosis only" concerning hippocampal and amygdala aspect, volumes, and signal intensity (SI) using Fisher's exact test, Student's t test, and principal component analysis. Visually, the ipsilateral hippocampus was hyperintense in both groups, but SI was markedly increased in 74% of HS and in 25% of "gliosis only" patients; the ipsilateral hippocampus was smaller in 92% of HS and in 50% of "gliosis only" patients, and its internal architecture was lost in 57% of HS and 5% of "gliosis only" patients; the contralateral hippocampal SI was altered in 25% of HS and in 70% of "gliosis only" patients (all p w signal intensity, preservation of internal architecture, and more contralateral affection.

  15. Childhood maltreatment, psychopathology, and the development of hippocampal subregions during adolescence.

    Science.gov (United States)

    Whittle, Sarah; Simmons, Julian G; Hendriksma, Sylke; Vijayakumar, Nandita; Byrne, Michelle L; Dennison, Meg; Allen, Nicholas B

    2017-02-01

    It is well established that childhood maltreatment has a detrimental impact on the brain, particularly the hippocampus. However, the hippocampus is a functionally and structurally heterogeneous region, and little is known about how maltreatment might affect hippocampal subregion development throughout important periods of plasticity. This study investigated whether childhood maltreatment was associated with the development of hippocampal subregion volumes from early to late adolescence. It also investigated associations between onset of psychiatric disorder and hippocampal subregion volume development. One hundred and sixty-six (85 male) adolescents took part in three magnetic resonance imaging assessments during adolescence (mean age at each assessment: 12.79 [ SD 0.43] years, 16.70 [ SD 0.52] years, and 19.08 [ SD 0.46] years), provided a self-report of childhood maltreatment, and were assessed for Axis I psychopathology. Childhood maltreatment was associated with the development of right total and left cornu ammonis 4 (CA4-DG) volumes from early to late adolescence. Early and late onset psychopathology was associated with the development of right presubiculum and right cornu ammonis 1 (CA1) volumes, respectively. Maltreatment findings appeared to be specific to males, whereas psychopathology findings appeared to be specific to females. These findings provide evidence for possible deleterious effects of childhood maltreatment and early onset psychiatric disorder on the development of different subregions of the hippocampus. Altered development of the right CA1, on the other hand, might precede the development of late-adolescent onset psychopathology. Our results highlight the importance of considering development in research examining associations between stress, mental illness, and hippocampal morphology.

  16. Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Overweight and Increased Adiposity at Adulthood in Male Rat Offspring.

    Science.gov (United States)

    Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosarío Noemí; Alén, Francisco; Antón, María; Decara, Juan; Arco, Rocío; Ouro, Daniel; Orio, Laura; Suárez, Juan; Lutz, Beat; Gómez de Heras, Raquel; Rodríguez de Fonseca, Fernando

    2016-01-01

    Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult male offspring. We found that calorie-restricted dams tended to have a reduced litter size, although the offspring showed normal weight at birth. Pups from calorie-restricted dams also exhibited a strong decrease in the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), arachidonic acid (AA) and palmitoylethanolamide (PEA) in the hypothalamus at birth. Additionally, pups from diet-restricted dams displayed reduced levels of AEA in the hippocampus without significant differences in the olfactory bulb. Moreover, offspring exhibited increased weight gain, body weight and adiposity in adulthood as well as increased anxiety-related responses. We propose that endocannabinoid signaling is altered by a maternal caloric restriction implemented during the preconceptional and pregnancy periods, which might lead to modifications of the hypothalamic and hippocampal circuits, potentially contributing to the long-term effects found in the adult offspring.

  17. Rhinal-hippocampal EEG coherence is reduced during human sleep.

    NARCIS (Netherlands)

    Fell, J.; Staedtgen, M.; Burr, W.; Kockelmann, E.; Helmstaedter, C.; Schaller, C.; Elger, C.E.; Fernandez, G.S.E.

    2003-01-01

    The deficiency of declarative memory compared with waking state is an often overlooked characteristic of sleep. Here, we investigated whether rhinal-hippocampal coherence, an electrophysiological correlate of declarative memory formation, is significantly altered during sleep as compared with waking

  18. Electroencephalography reveals lower regional blood perfusion and atrophy of the temporoparietal network associated with memory deficits and hippocampal volume reduction in mild cognitive impairment due to Alzheimer’s disease

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    Moretti DV

    2015-02-01

    Full Text Available Davide Vito MorettiNational Institute for the research and cure of Alzheimer’s disease, S. John of God, Fatebenefratelli, Brescia, Italy Background: An increased electroencephalographic (EEG upper/lower alpha power ratio has been associated with less regional blood perfusion, atrophy of the temporoparietal region of the brain, and reduction of hippocampal volume in subjects affected by mild cognitive impairment due to Alzheimer’s disease as compared with subjects who do not develop the disease. Moreover, EEG theta frequency activity is quite different in these groups. This study investigated the correlation between biomarkers and memory performance.Methods: EEG α3/α2 power ratio and cortical thickness were computed in 74 adult subjects with prodromal Alzheimer’s disease. Twenty of these subjects also underwent assessment of blood perfusion by single-photon emission computed tomography (SPECT. Pearson’s r was used to assess the correlation between cortical thinning, brain perfusion, and memory impairment.Results: In the higher α3/α2 frequency power ratio group, greater cortical atrophy and lower regional perfusion in the temporoparietal cortex was correlated with an increase in EEG theta frequency. Memory impairment was more pronounced in the magnetic resonance imaging group and SPECT groups.Conclusion: A high EEG upper/low alpha power ratio was associated with cortical thinning and less perfusion in the temporoparietal area. Moreover, atrophy and less regional perfusion were significantly correlated with memory impairment in subjects with prodromal Alzheimer’s disease. The EEG upper/lower alpha frequency power ratio could be useful for identifying individuals at risk for progression to Alzheimer’s dementia and may be of value in the clinical context.Keywords: electroencephalography, perfusion, atrophy, temporoparietal network, memory deficits, hippocampal volume, mild cognitive impairment, Alzheimer’s disease

  19. Age at developmental cortical injury differentially Alters corpus callosum volume in the rat

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    Rosen Glenn D

    2007-11-01

    Full Text Available Abstract Background Freezing lesions to developing rat cortex induced between postnatal day (P one and three (P1 – 3 lead to malformations similar to human microgyria, and further correspond to reductions in brain weight and cortical volume. In contrast, comparable lesions on P5 do not produce microgyric malformations, nor the changes in brain weight seen with microgyria. However, injury occurring at all three ages does lead to rapid auditory processing deficits as measured in the juvenile period. Interestingly, these deficits persist into adulthood only in the P1 lesion case 1. Given prior evidence that early focal cortical lesions induce abnormalities in cortical morphology and connectivity 1234, we hypothesized that the differential behavioral effects of focal cortical lesions on P1, P3 or P5 may be associated with underlying neuroanatomical changes that are sensitive to timing of injury. Clinical studies indicate that humans with perinatal brain injury often show regional reductions in corpus callosum size and abnormal symmetry, which frequently correspond to learning impairments 567. Therefore, in the current study the brains of P1, 3 or 5 lesion rats, previously evaluated for brain weight, and cortical volume changes and auditory processing impairments (P21-90, were further analyzed for changes in corpus callosum volume. Results Results showed a significant main effect of Treatment on corpus callosum volume [F (1,57 = 10.2, P Conclusion Decrements in corpus callosum volume in the P1 and 3 lesion groups are consistent with the reductions in brain weight and cortical volume previously reported for microgyric rats 18. Current results suggest that disruption to the cortical plate during early postnatal development may lead to more widely dispersed neurovolumetric anomalies and subsequent behavioral impairments 1, compared with injury that occurs later in development. Further, these results suggest that in a human clinical setting decreased

  20. Altered grey matter volume and cortical thickness in patients with schizo-obsessive comorbidity

    DEFF Research Database (Denmark)

    Wang, Yongming; Zou, Lai-quan; Xie, Wen-lan

    2018-01-01

    Recent findings suggest that schizo-obsessive comorbidity (SOC) may be a unique diagnostic entity. We examined grey matter (GM) volume and cortical thickness in 22 patients with SOC, and compared them with 21 schizophrenia (SCZ) patients, 22 obsessive-compulsive disorder (OCD) patients and 22...... healthy controls (HCs). We found that patients with SOC exhibited reduced GM volume in the left thalamus, the left inferior semi-lunar lobule of the cerebellum, the bilateral medial orbitofrontal cortex (medial oFC), the medial superior frontal gyrus (medial sFG), the rectus gyrus and the anterior...

  1. Hippocampal Abnormalities after Prolonged Febrile Convulsions

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available Hippocampal volume and T2 relaxation times were determined in an MRI study of 14 children with prolonged febrile convulsions (PFC who were investigated, 1 within 5 days of a PFC, and 2 at follow-up 4-8 months after the acute study, at the Institute of Child Health, University College, and Great Ormond Street Hospital, London, UK.

  2. Adult hippocampal neurogenesis and cognitive aging

    Directory of Open Access Journals (Sweden)

    Román Darío Moreno Fernández

    2013-12-01

    Full Text Available Aging is a normal developmental process associated with neurobiological changes leading to cognitive alterations with preserved, impaired, and enhanced functions. Evidence from animal and human studies is reviewed to explore the potential role of hippocampal plasticity on age-related cognitive changes with special attention to adult hippocampal neurogenesis. Results from lesion and stimulation strategies, as well as correlation data, support either a direct or modulatory role for adult newborn neurons in cognition at advanced ages. Further research on this topic may help to develop new treatments and to improve the quality of life of older people.

  3. Hippocampal polysynaptic computation.

    Science.gov (United States)

    Kimura, Rie; Kang, Siu; Takahashi, Naoya; Usami, Atsushi; Matsuki, Norio; Fukai, Tomoki; Ikegaya, Yuji

    2011-09-14

    Neural circuitry is a self-organizing arithmetic device that converts input to output and thereby remodels its computational algorithm to produce more desired output; however, experimental evidence regarding the mechanism by which information is modified and stored while propagating across polysynaptic networks is sparse. We used functional multineuron calcium imaging to monitor the spike outputs from thousands of CA1 neurons in response to the stimulation of two independent sites of the dentate gyrus in rat hippocampal networks ex vivo. Only pyramidal cells were analyzed based on post hoc immunostaining. Some CA1 pyramidal cells were observed to fire action potentials only when both sites were simultaneously stimulated (AND-like neurons), whereas other neurons fired in response to either site of stimulation but not to concurrent stimulation (XOR-like neurons). Both types of neurons were interlaced in the same network and altered their logical operation depending on the timing of paired stimulation. Repetitive paired stimulation for brief periods induced a persistent reorganization of AND and XOR operators, suggesting a flexibility in parallel distributed processing. We simulated these network functions in silico and found that synaptic modification of the CA3 recurrent excitation is pivotal to the shaping of logic plasticity. This work provides new insights into how microscopic synaptic properties are associated with the mesoscopic dynamics of complex microcircuits.

  4. Cortical Volume Alterations in Conduct Disordered Adolescents with and without Bipolar Disorder

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    Rene L. Olvera

    2014-04-01

    Full Text Available Background: There is increasing evidence that bipolar disorder (BD and conduct disorder (CD are co-occurring disorders. Magnetic resonance imaging has revealed differences in the structure and function of the frontal cortex in these disorders when studied separately; however, the impact of BD comorbidity on brain structure in adolescents with CD has not yet been examined. Method: We conducted an optimized voxel based morphometry (VBM study of juvenile offenders with the following diagnoses: conduct disorder with comorbid bipolar disorder (CD-BD; n = 24, conduct disorder without bipolar disorder (CD; n = 24 and healthy controls (HC, n = 24. Participants were 13–17 years of age, in a residential treatment facility for repeat offenders. The three groups in this study were similar in age, gender, socioeconomic status and ethnicity. Results: We found CD-BD subjects had decreased volume relative to controls at the voxel level in the right medial prefrontal cortex (PFC. Using a Threshold-Free Cluster Enhancement (TFCE technique, the CD-BD subjects had significantly decreased volumes of the right medial prefrontal cortex and portions of the superior and inferior frontal gyrus, anterior cingulate and temporal gyrus. The CD subjects did not have differences in brain volume compared to control subjects or CD-BD subjects. Conclusions: Our findings suggest the comorbidity between CD and BD is associated with neurobiological impact namely volumetric differences from healthy controls. Furthermore subjects with this comorbidity had poorer lifetime functioning, more mood and attentional dysfunction, and more medication exposure than subjects with CD who were not BD.

  5. Altered grey matter volume and cortical thickness in patients with schizo-obsessive comorbidity

    DEFF Research Database (Denmark)

    Wang, Yong-Ming; Zou, Lai-Quan; Xie, Wen-Lan

    2018-01-01

    cingulate cortex (aCC) compared with HCs. Patients with SOC also exhibited reduced cortical thickness in the right superior temporal gyrus (sTG), the right angular gyrus, the right supplementary motor area (SMA), the right middle cingulate cortex (mCC) and the right middle occipital gyrus (mOG) compared...... healthy controls (HCs). We found that patients with SOC exhibited reduced GM volume in the left thalamus, the left inferior semi-lunar lobule of the cerebellum, the bilateral medial orbitofrontal cortex (medial oFC), the medial superior frontal gyrus (medial sFG), the rectus gyrus and the anterior...

  6. Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease.

    Science.gov (United States)

    Quiroz, Yakeel T; Budson, Andrew E; Celone, Kim; Ruiz, Adriana; Newmark, Randall; Castrillón, Gabriel; Lopera, Francisco; Stern, Chantal E

    2010-12-01

    The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer's disease (FAD) provides a unique model for studying the early presymptomatic disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively-intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to develop the first symptoms of the disease around the age of 45 years. Our objective was to examine hippocampal function years before the onset of clinical symptoms. Twenty carriers of the Alzheimer's-associated E280A PS1 mutation and 19 PS1-negative control subjects participated. Both groups were matched for age, sex, education level, and neuropsychological test performance. All participants performed a face-name associative encoding task while in a Phillips 1.5T fMRI scanner. Analysis focused on the hippocampal system. Despite identical behavioral performance, presymptomatic PS1 mutation carriers exhibited increased activation of the right anterior hippocampus during encoding of novel face-name associations compared to matched controls. Our results demonstrate that functional changes within the hippocampal memory system occur years before cognitive decline in FAD. These presymptomatic changes in hippocampal physiology in FAD suggest that hippocampal fMRI patterns during associative encoding may also provide a preclinical biomarker in sporadic AD.

  7. Hippocampal Atrophy and Subsequent Depressive Symptoms in Older Men and Women: Results From a 10-Year Prospective Cohort

    Science.gov (United States)

    Elbejjani, Martine; Fuhrer, Rebecca; Abrahamowicz, Michal; Mazoyer, Bernard; Crivello, Fabrice; Tzourio, Christophe; Dufouil, Carole

    2014-01-01

    Several studies have reported smaller hippocampal volume in patients with depression. However, the temporality of the association is undetermined. One hypothesis is that hippocampal atrophy might be a susceptibility factor for depression. In the present study, we assessed whether hippocampal atrophy was associated with subsequent depressive symptoms in a cohort of older French adults (n = 1,309) who were 65–80 years of age and enrolled into the study in 1999–2001 in Dijon, France. Subjects were followed for more than 10 years. Participants underwent 2 cerebral magnetic resonance imaging scans, one at baseline and one at the 4-year follow-up. We used linear mixed models to estimate the associations of hippocampal atrophy with 1) the average depressive symptom scores over follow-up (using the Center for Epidemiologic Studies-Depression scale) measured biennially over the subsequent 6 years and 2) changes in symptom scores over follow-up. In women, a 2-standard-deviation increase in annual hippocampal atrophy was associated with a 1.67-point (95% confidence interval: 0.59, 2.77) increase in the average depressive symptom score over follow-up and with a 1.97-point (95% confidence interval: 0.68, 3.24) increase in scores over the 2 subsequent years but not with later changes in symptoms. No association was detected in men. Accounting for potential selective attrition (using inverse probability weights) did not alter results. Hippocampal atrophy was associated with more subsequent depressive symptoms and with shorter-term worsening of symptoms in women. PMID:25086051

  8. Expectation and expectoration: Information manipulation alters spitting volume, a common proxy for salivary flow.

    Science.gov (United States)

    Running, Cordelia A; Hayes, John E

    2016-12-01

    Saliva is becoming an increasingly useful research material across multiple fields of inquiry, including biomedical, dental, psychological, nutritional, and food choice research. However, both the flow rate and protein composition of stimulated saliva differ as a function of the collection method. We hypothesized that the context in which a stimulus is presented to participants may alter salivation via top down cognitive effects and/or behavioral changes (i.e., spitting efficiency). We presented participants with one stimulus (commercially available green tea) in two distinct contexts, once where the tea was described as a food item ("tea") and once where it was described as a disgusting non-food item ("rabbit hair extract"). Saliva and the expectorated stimulus were collected following 15s of oral exposure in a crossover design with the identical stimulus presented in both contexts; saliva was also collected for 5min after stimulation while chewing a piece of wax. Participants also completed validated personality instruments to measure food involvement, sensation seeking, sensitivity to reward, and sensitivity to punishment. Our data suggest participants spat out more sample when told they received the 'non-food' stimulus compared to the 'food' stimulus, particularly when they were given the non-food stimulus first. Further, individuals who were higher in sensation seeking spat out more sample during the 'food' condition compared to individuals with lower sensation seeking scores, but this difference was absent in the 'non-food' condition. While consistent with a top down cognitive effect on salivary flow, we believe a greater motivation to spit out the 'non-food' stimulus is a more likely explanation. In either case, it is clear the context in which a stimulus is presented alters how much sample/saliva is expectorated, suggesting context needs to be carefully considered in future work on salivary flow. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Predicting memory performance in normal ageing using different measures of hippocampal size

    International Nuclear Information System (INIS)

    Lye, T.C.; Creasey, H.; Kril, J.J.; Grayson, D.A.; Piguet, O.; Bennett, H.P.; Ridley, L.J.; Broe, G.A.

    2006-01-01

    A number of different methods have been employed to correct hippocampal volumes for individual variation in head size. Researchers have previously used qualitative visual inspection to gauge hippocampal atrophy. The purpose of this study was to determine the best measure(s) of hippocampal size for predicting memory functioning in 102 community-dwelling individuals over 80 years of age. Hippocampal size was estimated using magnetic resonance imaging (MRI) volumetry and qualitative visual assessment. Right and left hippocampal volumes were adjusted by three different estimates of head size: total intracranial volume (TICV), whole-brain volume including ventricles (WB+V) and a more refined measure of whole-brain volume with ventricles extracted (WB). We compared the relative efficacy of these three volumetric adjustment methods and visual ratings of hippocampal size in predicting memory performance using linear regression. All four measures of hippocampal size were significant predictors of memory performance. TICV-adjusted volumes performed most poorly in accounting for variance in memory scores. Hippocampal volumes adjusted by either measure of whole-brain volume performed equally well, although qualitative visual ratings of the hippocampus were at least as effective as the volumetric measures in predicting memory performance in community-dwelling individuals in the ninth or tenth decade of life. (orig.)

  10. Neuropathologic correlates of hippocampal atrophy in the elderly: a clinical, pathologic, postmortem MRI study.

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    Robert J Dawe

    Full Text Available The volume of the hippocampus measured with structural magnetic resonance imaging (MRI is increasingly used as a biomarker for Alzheimer's disease (AD. However, the neuropathologic basis of structural MRI changes in the hippocampus in the elderly has not been directly assessed. Postmortem MRI of the aging human brain, combined with histopathology, could be an important tool to address this issue. Therefore, this study combined postmortem MRI and histopathology in 100 elderly subjects from the Rush Memory and Aging Project and the Religious Orders Study. First, to validate the information contained in postmortem MRI data, we tested the hypothesis that postmortem hippocampal volume is smaller in subjects with clinically diagnosed Alzheimer's disease compared to subjects with mild or no cognitive impairment, as observed in antemortem imaging studies. Subsequently, the relations of postmortem hippocampal volume to AD pathology, Lewy bodies, amyloid angiopathy, gross infarcts, microscopic infarcts, and hippocampal sclerosis were examined. It was demonstrated that hippocampal volume was smaller in persons with a clinical diagnosis of AD compared to those with no cognitive impairment (P = 2.6 × 10(-7 or mild cognitive impairment (P = 9.6 × 10(-7. Additionally, hippocampal volume was related to multiple cognitive abilities assessed proximate to death, with its strongest association with episodic memory. Among all pathologies investigated, the most significant factors related to lower hippocampal volume were shown to be AD pathology (P = 0.0018 and hippocampal sclerosis (P = 4.2 × 10(-7. Shape analysis allowed for visualization of the hippocampal regions most associated with volume loss for each of these two pathologies. Overall, this investigation confirmed the relation of hippocampal volume measured postmortem to clinical diagnosis of AD and measures of cognition, and concluded that both AD pathology and hippocampal sclerosis affect hippocampal

  11. Aerobic fitness, hippocampal viscoelasticity, and relational memory performance.

    Science.gov (United States)

    Schwarb, Hillary; Johnson, Curtis L; Daugherty, Ana M; Hillman, Charles H; Kramer, Arthur F; Cohen, Neal J; Barbey, Aron K

    2017-06-01

    The positive relationship between hippocampal structure, aerobic fitness, and memory performance is often observed among children and older adults; but evidence of this relationship among young adults, for whom the hippocampus is neither developing nor atrophying, is less consistent. Studies have typically relied on hippocampal volumetry (a gross proxy of tissue composition) to assess individual differences in hippocampal structure. While volume is not specific to microstructural tissue characteristics, microstructural differences in hippocampal integrity may exist even among healthy young adults when volumetric differences are not diagnostic of tissue health or cognitive function. Magnetic resonance elastography (MRE) is an emerging noninvasive imaging technique for measuring viscoelastic tissue properties and provides quantitative measures of tissue integrity. We have previously demonstrated that individual differences in hippocampal viscoelasticity are related to performance on a relational memory task; however, little is known about health correlates to this novel measure. In the current study, we investigated the relationship between hippocampal viscoelasticity and cardiovascular health, and their mutual effect on relational memory in a group of healthy young adults (N=51). We replicated our previous finding that hippocampal viscoelasticity correlates with relational memory performance. We extend this work by demonstrating that better aerobic fitness, as measured by VO 2 max, was associated with hippocampal viscoelasticity that mediated the benefits of fitness on memory function. Hippocampal volume, however, did not account for individual differences in memory. Therefore, these data suggest that hippocampal viscoelasticity may provide a more sensitive measure to microstructural tissue organization and its consequences to cognition among healthy young adults. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Extra-Hippocampal Subcortical Limbic Involvement Predicts Episodic Recall Performance in Multiple Sclerosis

    Science.gov (United States)

    Dineen, Robert A.; Bradshaw, Christopher M.; Constantinescu, Cris S.; Auer, Dorothee P.

    2012-01-01

    Background Episodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging. Methodology/Principal Findings 34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, Pfornix FA and mammillary bodies as predictor of visual recall (R2 = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R2 = .37, P<.0005). No limbic measures predicted verbal recognition or verbal fluency. Conclusions/Significance These findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction. PMID:23056187

  13. Altered mean platelet volume in patients with polymyositis and its association with disease severity

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    Y.-F. Peng

    2016-01-01

    Full Text Available Polymyositis (PM is an autoimmune disease characterized by chronic inflammation in skeletal muscle. Mean platelet volume (MPV, a marker in the assessment of systemic inflammation, is easily measured by automatic blood count equipment. However, to our knowledge, there are no data in the literature with respect to MPV levels in PM patients. Therefore, in this study we aimed to investigate MPV levels in patients with PM. This study included 92 newly diagnosed PM patients and 100 healthy individuals. MPV levels were found to be significantly lower compared with healthy controls (10.3±1.23 vs 11.5±0.74 fL, P<0.001. Interestingly, MPV was found to be positively correlated with manual muscle test (MMT score and negatively correlated with erythrocyte sedimentation rate (ESR in patients with PM (r=0.239, P=0.022; r=−0.268, P=0.010, respectively. In addition, MPV was significantly lower in active PM patients compared with inactive PM patients (9.9±1.39 vs 10.6±0.92 fL, P=0.010. MPV was independently associated with PM in multivariate regression analyses, when controlling for hemoglobin and ESR (OR=0.312, P=0.031, 95%CI=0.108 to 0.899. The ROC curve analysis for MPV in estimating PM patients resulted in an area under the curve of 0.800, with sensitivity of 75.0% and specificity of 67.4%. Our results suggest that MPV is inversely correlated with disease activity in patients with PM. MPV might be a useful tool for rapid assessment of disease severity in PM patients.

  14. Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn H; Skimminge, Arnold; Rasmussen, Hans

    2011-01-01

    -weighted images (3 T) from 22 patients and 28 matched healthy controls were analysed using tensor-based morphometry. Non-parametric voxel-wise group comparisons were performed. Small volume correction was employed for striatum, hippocampus and ventricles. Dose-dependent medication effects and associations...

  15. Investigating the role of hippocampal BDNF in anxiety vulnerability using classical eyeblink conditioning

    Directory of Open Access Journals (Sweden)

    Kellie L Janke

    2015-07-01

    Full Text Available Dysregulation of brain-derived neurotrophic factor (BDNF, behavioral inhibition temperament (BI and small hippocampal volume have been linked to anxiety disorders. Individuals with BI show facilitated acquisition of the classically conditioned eyeblink response (CCER as compared to non-BI individuals, and a similar pattern is seen in an animal model of BI, the Wistar-Kyoto (WKY rat. The present study examined the role of hippocampal BDNF in the facilitated delay CCER of WKY rats. Consistent with earlier work, acquisition was facilitated in WKY rats compared to the SD rats. Facilitated acquisition was associated with increased BDNF, TrkB, and Arc mRNA in the dentate gyrus of SD rats, but learning-induced increases in BDNF and Arc mRNA were significantly smaller in WKY rats. To determine if reduced hippocampal BDNF in WKY rats was a contributing factor for their facilitated CCER, BDNF or saline infusions were given bilaterally into the dentate gyrus region one hour prior to training. BDNF infusion did not alter the acquisition of SD rats, but significantly dampened the acquisition of CCER in the WKY rats, such that acquisition was similar to SD rats. Together, these results suggest that inherent differences in the BDNF system play a critical role in the facilitated associative learning exhibited by WKY rats, and potentially individuals with BI. Facilitated associative learning may represent a vulnerability factor in the development of anxiety disorders.

  16. Hippocampal correlates of depression in healthy elderly adults.

    Science.gov (United States)

    Ezzati, Ali; Zimmerman, Molly E; Katz, Mindy J; Lipton, Richard B

    2013-12-01

    Mixed findings have been reported on the relationship between hippocampal integrity and major depression in clinical populations. Few neuroimaging studies have investigated associations between hippocampal measures and depressive symptoms in nondemented older adults. Here, we address this issue by imaging 36 nondemented adults over age 70 from the Einstein Aging Study, a community-based sample from the Bronx, NY. Depressive symptoms were assessed using the 15-item Geriatric Depression scale (GDS). Clinically significant depression was defined using a cut-off score of 5 or greater. Hippocampal data included MRI-derived volume data normalized to midsagittal area and MRS-derived N-acetylaspartate to creatine ratios (NAA/Cr). Our result indicates that smaller total hippocampal volume was associated with higher GDS scores, but there were no significant association between hippocampal NAA/Cr and GDS score. These effects were consistent after controlling for age, education, and gender. Reduction in hippocampal volume could represent a risk factor or a consequence of depression in older adults. Further studies are needed to better understand the role of the hippocampus in the development and experience of depression in older adults. Copyright © 2013 Wiley Periodicals, Inc.

  17. Semi-automatic classification of skeletal morphology in genetically altered mice using flat-panel volume computed tomography.

    Directory of Open Access Journals (Sweden)

    Christian Dullin

    2007-07-01

    Full Text Available Rapid progress in exploring the human and mouse genome has resulted in the generation of a multitude of mouse models to study gene functions in their biological context. However, effective screening methods that allow rapid noninvasive phenotyping of transgenic and knockout mice are still lacking. To identify murine models with bone alterations in vivo, we used flat-panel volume computed tomography (fpVCT for high-resolution 3-D imaging and developed an algorithm with a computational intelligence system. First, we tested the accuracy and reliability of this approach by imaging discoidin domain receptor 2- (DDR2- deficient mice, which display distinct skull abnormalities as shown by comparative landmark-based analysis. High-contrast fpVCT data of the skull with 200 microm isotropic resolution and 8-s scan time allowed segmentation and computation of significant shape features as well as visualization of morphological differences. The application of a trained artificial neuronal network to these datasets permitted a semi-automatic and highly accurate phenotype classification of DDR2-deficient compared to C57BL/6 wild-type mice. Even heterozygous DDR2 mice with only subtle phenotypic alterations were correctly determined by fpVCT imaging and identified as a new class. In addition, we successfully applied the algorithm to classify knockout mice lacking the DDR1 gene with no apparent skull deformities. Thus, this new method seems to be a potential tool to identify novel mouse phenotypes with skull changes from transgenic and knockout mice on the basis of random mutagenesis as well as from genetic models. However for this purpose, new neuronal networks have to be created and trained. In summary, the combination of fpVCT images with artificial neuronal networks provides a reliable, novel method for rapid, cost-effective, and noninvasive primary screening tool to detect skeletal phenotypes in mice.

  18. Acupuncture reversed hippocampal mitochondrial dysfunction in vascular dementia rats.

    Science.gov (United States)

    Li, Hui; Liu, Yi; Lin, Li-Ting; Wang, Xue-Rui; Du, Si-Qi; Yan, Chao-Qun; He, Tian; Yang, Jing-Wen; Liu, Cun-Zhi

    2016-01-01

    Hippocampal mitochondrial dysfunction due to oxidative stress has been considered to play a major role in the pathogenesis of vascular dementia (VD). Previous studies suggested that acupuncture could improve cerebral hypoperfusion-induced cognitive impairments. However, whether hippocampal mitochondria are associated with this cognitive improvement remains unclear. In this study, an animal model of VD was established via bilateral common carotid arteries occlusion (BCCAO) to investigate the alterations of cognitive ability and hippocampal mitochondrial function. BCCAO rats showed impairments in hippocampal mitochondrial function, overproduction of reactive oxygen species (ROS) and learning and memory deficits. After two-week acupuncture treatment, BCCAO-induced spatial learning and memory impairments as shown in Morris water maze were ameliorated. Hippocampal mitochondrial respiratory complex enzymes (complex I, II, IV) activities and cytochrome c oxidase IV expression significantly increased, which might contribute to the reduction of hippocampal ROS generation. In addition, acupuncture significantly improve mitochondrial bioenergy parameters such as mitochondrial respiratory control rate and membrane potential not PDH A1 expression. Placebo-acupuncture did not produce similar therapeutic effects. These findings suggested that acupuncture reversed BCCAO-induced hippocampal mitochondrial dysfunction, which might contribute to its prevention on cognitive deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Resveratrol: A Potential Hippocampal Plasticity Enhancer.

    Science.gov (United States)

    Dias, Gisele Pereira; Cocks, Graham; do Nascimento Bevilaqua, Mário Cesar; Nardi, Antonio Egidio; Thuret, Sandrine

    2016-01-01

    The search for molecules capable of restoring altered hippocampal plasticity in psychiatric and neurological conditions is one of the most important tasks of modern neuroscience. It is well established that neural plasticity, such as the ability of the postnatal hippocampus to continuously generate newly functional neurons throughout life, a process called adult hippocampal neurogenesis (AHN), can be modulated not only by pharmacological agents, physical exercise, and environmental enrichment, but also by "nutraceutical" agents. In this review we focus on resveratrol, a phenol and phytoalexin found in the skin of grapes and red berries, as well as in nuts. Resveratrol has been reported to have antioxidant and antitumor properties, but its effects as a neural plasticity inducer are still debated. The current review examines recent evidence implicating resveratrol in regulating hippocampal neural plasticity and in mitigating the effects of various disorders and diseases on this important brain structure. Overall, findings show that resveratrol can improve cognition and mood and enhance hippocampal plasticity and AHN; however, some studies report opposite effects, with resveratrol inhibiting aspects of AHN. Therefore, further investigation is needed to resolve these controversies before resveratrol can be established as a safe coadjuvant in preventing and treating neuropsychiatric conditions.

  20. Divergent Roles of Central Serotonin in Adult Hippocampal Neurogenesis

    Directory of Open Access Journals (Sweden)

    Ning-Ning Song

    2017-06-01

    Full Text Available The central serotonin (5-HT system is the main target of selective serotonin reuptake inhibitors (SSRIs, the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we review how changes in the central serotonergic system alter adult hippocampal neurogenesis. We focus on data obtained from three categories of genetically engineered mouse models: (1 mice with altered central 5-HT levels from embryonic stages, (2 mice with deletion of 5-HT receptors from embryonic stages, and (3 mice with altered central 5-HT system exclusively in adulthood. These recent findings provide unique insights to interpret the multifaceted roles of central 5-HT on adult hippocampal neurogenesis and its associated effects on depression.

  1. Impact of neonatal iron deficiency on hippocampal DNA methylation and gene transcription in a porcine biomedical model of cognitive development

    NARCIS (Netherlands)

    Schachtschneider, Kyle M.; Liu, Yingkai; Rund, Laurie A.; Madsen, Ole; Johnson, Rodney W.; Groenen, Martien A.M.; Schook, Lawrence B.

    2016-01-01


    Background

    Iron deficiency is a common childhood micronutrient deficiency that results in altered hippocampal function and cognitive disorders. However, little is known about the mechanisms through which neonatal iron deficiency results in long lasting alterations in hippocampal gene

  2. Roles of hippocampal subfields in verbal and visual episodic memory.

    Science.gov (United States)

    Zammit, Andrea R; Ezzati, Ali; Zimmerman, Molly E; Lipton, Richard B; Lipton, Michael L; Katz, Mindy J

    2017-01-15

    Selective hippocampal (HC) subfield atrophy has been reported in older adults with mild cognitive impairment and Alzheimer's disease. The goal of this study was to investigate the associations between the volume of hippocampal subfields and visual and verbal episodic memory in cognitively normal older adults. This study was conducted on a subset of 133 participants from the Einstein Aging Study (EAS), a community-based study of non-demented older adults systematically recruited from the Bronx, N.Y. All participants completed comprehensive EAS neuropsychological assessment. Visual episodic memory was assessed using the Complex Figure Delayed Recall subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Verbal episodic memory was assessed using Delayed Recall from the Free and Cued Selective Reminding Test (FCSRT). All participants underwent 3T MRI brain scanning with subsequent automatic measurement of the hemispheric hippocampal subfield volumes (CA1, CA2-CA3, CA4-dente gyrus, presubiculum, and subiculum). We used linear regressions to model the association between hippocampal subfield volumes and visual and verbal episodic memory tests while adjusting for age, sex, education, and total intracranial volume. Participants had a mean age of 78.9 (SD=5.1) and 60.2% were female. Total hippocampal volume was associated with Complex Figure Delayed Recall (β=0.31, p=0.001) and FCSRT Delayed Recall (β=0.27, p=0.007); subiculum volume was associated with Complex Figure Delayed Recall (β=0.27, p=0.002) and FCSRT Delayed Recall (β=0.24, p=0.010); CA1 was associated with Complex Figure Delayed Recall (β=0.26, pmemory. Our results suggest that hippocampal subfields have sensitive roles in the process of visual and verbal episodic memory. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Automated hippocampal segmentation in patients with epilepsy: Available free online

    Science.gov (United States)

    Winston, Gavin P; Cardoso, M Jorge; Williams, Elaine J; Burdett, Jane L; Bartlett, Philippa A; Espak, Miklos; Behr, Charles; Duncan, John S; Ourselin, Sebastien

    2013-01-01

    Purpose Hippocampal sclerosis, a common cause of refractory focal epilepsy, requires hippocampal volumetry for accurate diagnosis and surgical planning. Manual segmentation is time-consuming and subject to interrater/intrarater variability. Automated algorithms perform poorly in patients with temporal lobe epilepsy. We validate and make freely available online a novel automated method. Methods Manual hippocampal segmentation was performed on 876, 3T MRI scans and 202, 1.5T scans. A template database of 400 high-quality manual segmentations was used to perform automated segmentation of all scans with a multi-atlas–based segmentation propagation method adapted to perform label fusion based on local similarity to ensure accurate segmentation regardless of pathology. Agreement between manual and automated segmentations was assessed by degree of overlap (Dice coefficient) and comparison of hippocampal volumes. Key Findings The automated segmentation algorithm provided robust delineation of the hippocampi on 3T scans with no more variability than that seen between different human raters (Dice coefficients: interrater 0.832, manual vs. automated 0.847). In addition, the algorithm provided excellent results with the 1.5T scans (Dice coefficient 0.827), and automated segmentation remained accurate even in small sclerotic hippocampi. There was a strong correlation between manual and automated hippocampal volumes (Pearson correlation coefficient 0.929 on the left and 0.941 on the right in 3T scans). Significance We demonstrate reliable identification of hippocampal atrophy in patients with hippocampal sclerosis, which is crucial for clinical management of epilepsy, particularly if surgical treatment is being contemplated. We provide a free online Web-based service to enable hippocampal volumetry to be available globally, with consequent greatly improved evaluation of those with epilepsy. PMID:24151901

  4. Abnormal Hippocampal Morphology in Dissociative Identity Disorder and Post-Traumatic Stress Disorder Correlates with Childhood Trauma and Dissociative Symptoms

    NARCIS (Netherlands)

    Chalavi, Sima; Vissia, Eline M.; Giesen, Mechteld E.; Nijenhuis, Ellert R. S.; Draijer, Nel; Cole, James H.; Dazzan, Paola; Pariante, Carmine M.; Madsen, Sarah K.; Rajagopalan, Priya; Thompson, Paul M.; Toga, Arthur W.; Veltman, Dick J.; Reinders, Antje A. T. S.

    Smaller hippocampal volume has been reported in individuals with post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization

  5. Episodic autobiographical memory is associated with variation in the size of hippocampal subregions.

    Science.gov (United States)

    Palombo, Daniela J; Bacopulos, Agnes; Amaral, Robert S C; Olsen, Rosanna K; Todd, Rebecca M; Anderson, Adam K; Levine, Brian

    2018-02-01

    Striking individual differences exist in the human capacity to recollect past events, yet, little is known about the neural correlates of such individual differences. Studies investigating hippocampal volume in relation to individual differences in laboratory measures of episodic memory in young adults suggest that whole hippocampal volume is unrelated (or even negatively associated) with episodic memory. However, anatomical and functional specialization across hippocampal subregions suggests that individual differences in episodic memory may be linked to particular hippocampal subregions, as opposed to whole hippocampal volume. Given that the DG/CA 2/3 circuitry is thought to be especially critical for supporting episodic memory in humans, we predicted that the volume of this region would be associated with individual variability in episodic memory. This prediction was supported using high-resolution MRI of the hippocampal subfields and measures of real-world (autobiographical) episodic memory. In addition to the association with DG/CA 2/3 , we further observed a relationship between episodic autobiographical memory and subiculum volume, whereas no association was observed with CA 1 or with whole hippocampal volume. These findings provide insight into the possible neural substrates that mediate individual differences in real-world episodic remembering in humans. © 2017 Wiley Periodicals, Inc.

  6. The alterations of cortical volume, thickness, surface and density in the intermediate sporadic Parkinson's disease from the Han population of Mainland China

    Directory of Open Access Journals (Sweden)

    Xia Deng

    2016-08-01

    Full Text Available Many symptoms of sporadic Parkinson's disease (sPD can’t be completely explained by the lesion of simple typical extrapyramidal circuit between striatum and substantia nigra. Therefore, we investigated the alteration of cortical volume, thickness, surface and density in the intermediate sPD from the Han population of Mainland China in order to find the new pathological brain regions associated with the complex clinical manifestations of sPD. The cortical volume, thickness, surface and density were examined using the voxel-based cortical morphometry and corticometry on magnetic resonance image (MRI in 67 intermediate sPD and 35 controls, the multiple adjusted comparisons analysis of all MRI data were employed to assess the relationships between the cortical morphometric alteration in the specific brain regions and sPD. Results showed that a significantly shrunk volume, thinned thickness and enlarged or reduced surface of cortex in some specific brain regions were closely associated with sPD, but all cortical densities were not different. The majority of morphometric alteration of hemisphere cortex was symmetric, but that in the left hemisphere was more significant. The cortical morphometric alterations in the frontal, temporal, parietal, occipital and limbic lobe, cerebellum, caudate and thalamus were closely related to the clinical neural dysfunction (Clinical manifestations of sPD. Our data indicated that the deficits of extensive brain regions involved in the development of sPD, resulted in a series of correspondent complex clinical manifestations in the disease.

  7. Modulation of Adult Hippocampal Neurogenesis by Sleep: Impact on Mental Health

    Directory of Open Access Journals (Sweden)

    Cristina Navarro-Sanchis

    2017-10-01

    Full Text Available The process of neurogenesis has been demonstrated to occur throughout life in the subgranular zone (SGZ of the hippocampal dentate gyrus of several mammals, including humans. The basal rate of adult hippocampal neurogenesis can be altered by lifestyle and environmental factors. In this perspective review, the evidence for sleep as a modulator of adult hippocampal neurogenesis is first summarized. Following this, the impacts of sleep and sleep disturbances on hippocampal-dependent functions, including learning and memory, and depression are critically evaluated. Finally, we postulate that the effects of sleep on hippocampal-dependent functions may possibly be mediated by a change in adult hippocampal neurogenesis. This could provide a route to new treatments for cognitive impairments and psychiatric disorders.

  8. Modulation of Adult Hippocampal Neurogenesis by Sleep: Impact on Mental Health

    Science.gov (United States)

    Navarro-Sanchis, Cristina; Brock, Olivier; Winsky-Sommerer, Raphaelle; Thuret, Sandrine

    2017-01-01

    The process of neurogenesis has been demonstrated to occur throughout life in the subgranular zone (SGZ) of the hippocampal dentate gyrus of several mammals, including humans. The basal rate of adult hippocampal neurogenesis can be altered by lifestyle and environmental factors. In this perspective review, the evidence for sleep as a modulator of adult hippocampal neurogenesis is first summarized. Following this, the impacts of sleep and sleep disturbances on hippocampal-dependent functions, including learning and memory, and depression are critically evaluated. Finally, we postulate that the effects of sleep on hippocampal-dependent functions may possibly be mediated by a change in adult hippocampal neurogenesis. This could provide a route to new treatments for cognitive impairments and psychiatric disorders. PMID:29075182

  9. Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Seibert, Tyler M.; Karunamuni, Roshan [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Bartsch, Hauke [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Kaifi, Samar [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Krishnan, Anitha Priya [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Dalia, Yoseph; Burkeen, Jeffrey; Murzin, Vyacheslav; Moiseenko, Vitali [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Kuperman, Joshua; White, Nathan S. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Brewer, James B. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Department of Neurosciences, University of California, San Diego, La Jolla, California (United States); Farid, Nikdokht [Department of Radiology, University of California, San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Psychiatry, University of California, San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States)

    2017-02-01

    Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI before and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for brain

  10. Relationships between hippocampal activity and breathing patterns

    DEFF Research Database (Denmark)

    Harper, R M; Poe, G R; Rector, D M

    1998-01-01

    Single cell discharge, EEG activity, and optical changes accompanying alterations in breathing patterns, as well as the knowledge that respiratory musculature is heavily involved in movement and other behavioral acts, implicate hippocampal regions in some aspects of breathing control. The control...... is unlikely to reside in oscillatory breathing movements, because such patterns emerge in preparations retaining only the medulla (and perhaps only the spinal cord). However, momentary changes in breathing patterns induced by affect, startle, whole-body movement changes, or compensatory ventilatory changes...... of hippocampal contributions to breathing control should be viewed in the context that significant interactions exist between blood pressure changes and ventilation, and that modest breathing challenges, such as exposure to hypercapnia or to increased resistive loads, bring into action a vast array of brain...

  11. Prediction of dementia by hippocampal shape analysis

    DEFF Research Database (Denmark)

    Achterberg, Hakim C.; van der Lijn, Fedde; den Heijer, Tom

    2010-01-01

    This work investigates the possibility of predicting future onset of dementia in subjects who are cognitively normal, using hippocampal shape and volume information extracted from MRI scans. A group of 47 subjects who were non-demented normal at the time of the MRI acquisition, but were diagnosed...... with dementia during a 9 year follow-up period, was selected from a large population based cohort study. 47 Age and gender matched subjects who stayed cognitively intact were selected from the same cohort study as a control group. The hippocampi were automatically segmented and all segmentations were inspected...... and, if necessary, manually corrected by a trained observer. From this data a statistical model of hippocampal shape was constructed, using an entropy-based particle system. This shape model provided the input for a Support Vector Machine classifier to predict dementia. Cross validation experiments...

  12. PROPYLTHIOURACIL (PTU)-INDUCED HYPOTHYROIDISM: EFFECTS ON SYNAPTIC TRANSMISSION AND LONG TERM POTENTIATION IN HIPPOCAMPAL SLICES.

    Science.gov (United States)

    Concern has been raised over endocrine effects of some classes of environmental chemicals. Severe hypothyroidism during critical periods of brain developmental leads to alterations in hippocampal structure, learning deficits, yet neurophysiological properties of the hippocampus...

  13. Altered sexually dimorphic nucleus of the preoptic area (SDN-POA) volume in adult Long-Evans rats by dietary soy phytoestrogens.

    Science.gov (United States)

    Lund, T D; Rhees, R W; Setchell, K D; Lephart, E D

    2001-09-28

    Naturally occurring estrogen-like molecules in plants (phytoestrogens), present via soy, in animal diets can alter morphology and physiology in rodents. Phytoestrogens have the ability to bind estrogen receptors and exert many of the biological responses evoked by physiological estrogens. This study characterized the effects of dietary phytoestrogens on the expression of body and prostate weight, circulating testosterone and estradiol levels, puberty onset, vaginal cyclicity, and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in Long-Evans rats. Using different experimental protocols, animals were fed either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free) diet. Animals fed the Phyto-600 diet displayed significantly decreased body weights (in males and females), prostate weights and delayed puberty in females compared to that of animals fed the Phyto-free diet. Circulating testosterone or estradiol levels in males or estrous cyclicity were not altered by the diets. The volume of the SDN-POA was significantly altered by a change in diet at 80 days of age where one-half of the males or females fed the Phyto-600 diet (from birth) were switched to the Phyto-free diet until 120 days of age. Males initially fed a Phyto-600 diet but changed to a Phyto-free diet had significantly smaller SDN-POA volumes compared to males fed the Phyto-600 diet (long-term). These data suggest that consumption of phytoestrogens via a soy diet, significantly: (1) decreases body and prostate weight, (2) delays puberty onset, and (3) alters SDN-POA volumes during adulthood.

  14. Adult Hippocampal Neurogenesis is Impaired by Transient and Moderate Developmental Thyroid Hormone Disruption

    Science.gov (United States)

    Severe thyroid hormone (TH) deprivation during development impairs neurogenesis throughout the brain. The hippocampus also maintains a capacity for neurogenesis throughout life which is reduced in adult-onset hypothyroidism. This study examined hippocampal volume in the neonate a...

  15. Qualitative and Quantitative Hippocampal MRI Assessments in Intractable Epilepsy

    Directory of Open Access Journals (Sweden)

    Paramdeep Singh

    2013-01-01

    Full Text Available Aims. To acquire normative data of hippocampal volumes and T2 relaxation times, to evaluate and compare qualitative and quantitative assessments in evaluating hippocampi in patients with different durations of intractable epilepsy, and to propose an imaging protocol based on performance of these techniques. Methods. MRI analysis was done in 50 nonepileptic controls and 30 patients with intractable epilepsy on 1.5T scanner. Visual assessment and hippocampal volumetry were done on oblique coronal IR/T2W and T1W MP-RAGE images, respectively. T2 relaxation times were measured using 16-echo Carr-Purcell-Meiboom-Gill sequence. Volumetric data was normalized for variation in head size between individuals. Patients were divided into temporal ( and extratemporal ( groups based on clinical and EEG localization. Results. In controls, right hippocampal volume was slightly more than the left with no effect of age or gender. In TLE patients, hippocampal volumetry provided maximum concordance with EEG. Visual assessment of unilateral pathology concurred well with measured quantitative values but poorly in cases with bilateral pathologies. There were no significant differences of mean values between extratemporal group and controls group. Quantitative techniques detected mild abnormalities, undetected on visual assessment. Conclusions. Quantitative techniques are more sensitive to diagnose bilateral and mild unilateral hippocampal abnormalities.

  16. Tuberous sclerosis complex coexistent with hippocampal sclerosis.

    Science.gov (United States)

    Lang, Min; Prayson, Richard A

    2016-02-01

    Tuberous sclerosis and hippocampal sclerosis are both well-defined entities associated with medically intractable epilepsy. To our knowledge, there has been only one prior case of these two pathologies being co-existent. We report a 7-month-old boy who presented with intractable seizures at 2 months of age. MRI studies showed diffuse volume loss in the brain with bilateral, multiple cortical tubers and subcortical migration abnormalities. Subependymal nodules were noted without subependymal giant cell astrocytoma. Genetic testing revealed TSC2 and PRD gene deletions. Histopathology of the hippocampus showed CA1 sclerosis marked by loss of neurons in the CA1 region. Sections from the temporal, parietal and occipital lobes showed multiple cortical tubers characterized by cortical architectural disorganization, gliosis, calcifications and increased number of large balloon cells. Focal white matter balloon cells and spongiform changes were also present. The patient underwent resection of the right fronto-parietal lobe and a subsequent resection of the right temporal, parietal and occipital lobes. The patient is free of seizures on anti-epileptic medication 69 months after surgery. Although hippocampal sclerosis is well documented to be associated with coexistent focal cortical dysplasia, the specific co-existence of cortical tubers and hippocampal sclerosis appears to be rare. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Sub-regional hippocampal injury is associated with fornix degeneration in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Dong Young Lee

    2012-04-01

    Full Text Available We examined in vivo evidence of axonal degeneration in association with neuronal pathology in Alzheimer’s disease (AD through analysis of fornix microstructural integrity and measures of hippocampal subfield atrophy. Based on known anatomical topography, we hypothesized that the local thickness of subiculum and CA1 hippocampus fields would be associated with fornix integrity, reflecting an association between AD-related injury to hippocampal neurons and degeneration of associated axon fibers. To test this hypothesis, multi-modal imaging, combining measures of local hippocampal radii with diffusion tensor imaging (DTI, was applied to 44 individuals clinically diagnosed with AD, 44 individuals clinically diagnosed with mild cognitive impairment (MCI, and 96 cognitively normal individuals. Fornix microstructural degradation, as measured by reduced DTI-based fractional anisotropy (FA, was prominent in both MCI and AD, and was associated with reduced hippocampal volumes. Further, reduced fornix FA was associated with reduced anterior CA1 and antero-medial subiculum thickness. Finally, while both lesser fornix FA and lesser hippocampal volume were associated with lesser episodic memory, only the hippocampal measures were significant predictors of episodic memory in models including both hippocampal and fornix predictors. The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury.

  18. Sub-Regional Hippocampal Injury is Associated with Fornix Degeneration in Alzheimer’s Disease

    Science.gov (United States)

    Lee, Dong Young; Fletcher, Evan; Carmichael, Owen Thomas; Singh, Baljeet; Mungas, Dan; Reed, Bruce; Martinez, Oliver; Buonocore, Michael H.; Persianinova, Maria; DeCarli, Charles

    2012-01-01

    We examined in vivo evidence of axonal degeneration in association with neuronal pathology in Alzheimer’s disease (AD) through analysis of fornix microstructural integrity and measures of hippocampal subfield atrophy. Based on known anatomical topography, we hypothesized that the local thickness of subiculum and CA1 hippocampus fields would be associated with fornix integrity, reflecting an association between AD-related injury to hippocampal neurons and degeneration of associated axon fibers. To test this hypothesis, multi-modal imaging, combining measures of local hippocampal radii with diffusion tensor imaging (DTI), was applied to 44 individuals clinically diagnosed with AD, 44 individuals clinically diagnosed with mild cognitive impairment (MCI), and 96 cognitively normal individuals. Fornix microstructural degradation, as measured by reduced DTI-based fractional anisotropy (FA), was prominent in both MCI and AD, and was associated with reduced hippocampal volumes. Further, reduced fornix FA was associated with reduced anterior CA1 and antero-medial subiculum thickness. Finally, while both lesser fornix FA and lesser hippocampal volume were associated with lesser episodic memory, only the hippocampal measures were significant predictors of episodic memory in models including both hippocampal and fornix predictors. The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury. PMID:22514534

  19. Volumetric MRI and {sup 1}H MRS study of hippocampus in unilateral MCAO patients: Relationship between hippocampal secondary damage and cognitive disorder following stroke

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Xiangyu; Wang, Chengyuan; Xia, Liming [Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Dadao 1095, Wuhan 430030 (China); Zhu, Wenhao [Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Dadao 1095, Wuhan 430030 (China); Zhao, Lingyun [Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Dadao 1095, Wuhan 430030 (China); Zhu, Wenzhen, E-mail: zhuwenzhen@hotmail.com [Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Dadao 1095, Wuhan 430030 (China)

    2012-10-15

    Objective: To determine whether hippocampi alter in patients at the recovery stage of middle cerebral artery occlusion (MCAO) and whether the changes of hippocampi involve in the cognitive impairment in such patients. Meterials and methods: Forty-four patients with unilateral infarction solely in MCAO territory and 44 age-, sex- and education background-matched healthy volunteers were enrolled in this study. All subjects underwent 3-dimensional fast spoiled gradient-echo (3D FSPGR) and sing-voxel proton magnetic resonance spectroscopy ({sup 1}H MRS) protocols at a 1.5 T MR scanner. The ratios of n-acetylaspartate/creatine (NAA/Cr) and myo-inositol/creatine (mI/Cr) were obtained by using software integrated in the MR scanner. The hippocampal volumes were estimated by manually measurement. Results: The volume and NAA/Cr ratio were found significantly decreased and mI/Cr ratio significantly increased in the hippocampus ipsilateral to occluded middle cerebral artery (MCA) as compared with values in the contralateral hippocampus or healthy control. A reduced NAA/Cr ratio was also observed in contralateral hippocampus compared to controls. The shrinkage ratio of hippocampus ipsilateral to MCAO was found related to the Mini–Mental State Examination (MMSE) score. Conclusion: Our study identified that the hippocampal secondary damage occurred in patients after MCAO, and it could be evaluated noninvasively by volumetric magnetic resonance imaging (MRI) and {sup 1}H MRS. Moreover, the hippocampal secondary damage in MCAO patients indeed contributed to their cognitive impairment.

  20. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression

    DEFF Research Database (Denmark)

    Jørgensen, A.; Magnusson, P.; Hanson, Lars G.

    2016-01-01

    Objective: To investigate the role of hippocampal plasticity in the antidepressant effect of electroconvulsive therapy (ECT). Method: We used magnetic resonance (MR) imaging including diffusion tensor imaging (DTI) and proton MR spectroscopy (1 H- MRS) to investigate hippocampal volume, diffusivity...

  1. Abnormal Hippocampal Morphology in Dissociative Identity Disorder and Posttraumatic Stress Disorder Correlates with Childhood Trauma and Dissociative Symptoms

    Science.gov (United States)

    Chalavi, Sima; Vissia, Eline M.; Giesen, Mechteld E.; Nijenhuis, Ellert R.S.; Draijer, Nel; Cole, James H.; Dazzan, Paola; Pariante, Carmine M.; Madsen, Sarah K.; Rajagopalan, Priya; Thompson, Paul M.; Toga, Arthur W.; Veltman, Dick J.; Reinders, Antje A.T.S.

    2015-01-01

    Smaller hippocampal volume has been reported in individuals with posttraumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization are still unclear. Brain structural MRI scans were analyzed for 33 outpatients (17 with DID and 16 with PTSD only) and 28 healthy controls (HC), all matched for age, sex, and education. DID patients met criteria for PTSD (PTSD-DID). Hippocampal global and subfield volumes and shape measurements were extracted. We found that global hippocampal volume was significantly smaller in all 33 patients (left: 6.75%; right: 8.33%) compared to HC. PTSD-DID (left: 10.19%; right: 11.37%) and PTSD-only with a history of childhood traumatization (left: 7.11%; right: 7.31%) had significantly smaller global hippocampal volume relative to HC. PTSD-DID had abnormal shape and significantly smaller volume in the CA2-3, CA4-DG and (pre)subiculum compared to HC. In the patient groups, smaller global and subfield hippocampal volumes significantly correlated with higher severity of childhood traumatization and dissociative symptoms. These findings support a childhood trauma-related etiology for abnormal hippocampal morphology in both PTSD and DID and can further the understanding of neurobiological mechanisms involved in these disorders. PMID:25545784

  2. Abnormal hippocampal morphology in dissociative identity disorder and post-traumatic stress disorder correlates with childhood trauma and dissociative symptoms.

    Science.gov (United States)

    Chalavi, Sima; Vissia, Eline M; Giesen, Mechteld E; Nijenhuis, Ellert R S; Draijer, Nel; Cole, James H; Dazzan, Paola; Pariante, Carmine M; Madsen, Sarah K; Rajagopalan, Priya; Thompson, Paul M; Toga, Arthur W; Veltman, Dick J; Reinders, Antje A T S

    2015-05-01

    Smaller hippocampal volume has been reported in individuals with post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization are still unclear. Brain structural magnetic resonance imaging scans were analyzed for 33 outpatients (17 with DID and 16 with PTSD only) and 28 healthy controls (HC), all matched for age, sex, and education. DID patients met criteria for PTSD (PTSD-DID). Hippocampal global and subfield volumes and shape measurements were extracted. We found that global hippocampal volume was significantly smaller in all 33 patients (left: 6.75%; right: 8.33%) compared with HC. PTSD-DID (left: 10.19%; right: 11.37%) and PTSD-only with a history of childhood traumatization (left: 7.11%; right: 7.31%) had significantly smaller global hippocampal volume relative to HC. PTSD-DID had abnormal shape and significantly smaller volume in the CA2-3, CA4-DG and (pre)subiculum compared with HC. In the patient groups, smaller global and subfield hippocampal volumes significantly correlated with higher severity of childhood traumatization and dissociative symptoms. These findings support a childhood trauma-related etiology for abnormal hippocampal morphology in both PTSD and DID and can further the understanding of neurobiological mechanisms involved in these disorders. © 2014 Wiley Periodicals, Inc.

  3. Measuring the volume of the hippocampus in healthy Chinese adults of the Han nationality on the high-resolution MRI

    International Nuclear Information System (INIS)

    Zhang Yong; Chen Nan; Wang Xing; Li Kuncheng; Zhuo Yan; Chen Lin

    2010-01-01

    Objective: To measure the volume of hippocampal formation (HPF) in healthy Chinese Han adults and provide database for researching on a variety of diseases associated with alteration of hippocampal structure. Methods: This is a clinical multi-center study. One thousand Chinese healthy volunteers (age range=18 to 70) recruited from 15 hospitals were divided into 5 groups, i. e., Group A (age range=18 to 30), B (age range=31 to 40), C (age range =41 to 50), D (age range =51 to 60), and E (age range = 61 to 70). Each group contained 100 males and 100 females. All of the volunteers were scanned by MR using T 1 weighted three-dimensional magnetization prepared rapid acquisition gradient echo sequence. The margin of HPF were outlined manually for each side. Using multiple linear regression, relationships between hippocampal volume and sex, age, weight and height were analyzed respectively. Independent two sample t test was used to study the differences between male and female and between left and right. The differences of hippocampal volume among age groups were analyzed by ANOVA. Results: Hippocampal volume for left and right side were (4752±659) and (5032±660) mm 3 respectively. The volume of HPF is significant correlated with gender and age, but without relevance to height and weight (left and right r=0.283,0.311, F=30.127,37.050,P 3 respectively for men, and (4647±624) and (4904±630) mm 3 for women. The right hippocampal volume was larger than the left (t=7.030,6.696, P 3 respectively, while the volumes of the fight hippocampus were (5340± 647), (5276±582), (5264±620), (5133±661), (4894±699) mm 3 respectively. Among age groups, the differences were statistically significant (left and right F=5.737,7.607, P 0.05). There was no significant difference of hippocampal among different groups in women (P>0.05). Conclusions: With high-resolution MRI, the volume of the HPF was accurately measured, so as to provide the basic data for research of the hippocampus

  4. Investigation of the alteration of gray matter volume in children with mental retardation with the optimal voxel-based morphometry

    International Nuclear Information System (INIS)

    Yuan Xinyu; Xie Sheng; Xiao Jiangxi; Zhang Yuanzhe; Jiang Xuexiang; Jin Chunhua; Bai Zhenhua; Yi Xiaoli

    2011-01-01

    Objective: To detect brain structural difference between children with unexplained mental retardation and children with typically normal development. Methods: The high-resolution magnetic MR imaging were obtained from 21 children with unexplained mental retardation and 30 age-matched control children without intellectual disabilities. Voxel-based morphometry analysis with an optimization of spatial segmentation and normalization procedures were applied to compare differences of gray matter volume between the two groups. The total and regional gray matter volume were compared between the two groups with independent t test. Meanwhile, correlation was conducted to analyze the relationship between the total gray matter volume and intelligence quotient (IQ) with partial correlation test. Results: The total gray matter volume was significantly increased in the mental retardation children (1.012±0.079) × 10 6 mm 3 ] in relative to the controls [(0.956±0.059)×10 6 mm 3 , t=-2.80, P 0.05). Conclusions: VBM would detect the gray matter abnormalities that were not founded in routine MR scanning. The increase of gray matter volume in the frontal-thalamus network might indicate the delayed maturation of the brain development. This might be one of the causations of' mental retardation in children. (authors)

  5. Hippocampal Hyperactivation in Presymptomatic Familial Alzheimer’s Disease

    Science.gov (United States)

    Quiroz, Yakeel T.; Budson, Andrew E.; Celone, Kim; Ruiz, Adriana; Newmark, Randall; Castrillón, Gabriel; Lopera, Francisco; Stern, Chantal E.

    2011-01-01

    Objective The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer’s disease (FAD) provides a unique model for studying the early presymptomatic disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively-intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to develop the first symptoms of the disease around the age of 45 years. Our objective was to examine hippocampal function years before the onset of clinical symptoms. Methods Twenty carriers of the Alzheimer’s-associated E280A PS1 mutation and 19 PS1-negative control subjects participated. Both groups were matched for age, sex, education level, and neuropsychological test performance. All participants performed a face-name associative encoding task while in a Philips 1.5T fMRI scanner. Analysis focused on the hippocampal system. Results Despite identical behavioral performance, presymptomatic PS1 mutation carriers exhibited increased activation of the right anterior hippocampus during encoding of novel face-name associations compared to matched controls. Interpretation Our results demonstrate that functional changes within the hippocampal memory system occur years before cognitive decline in FAD. These presymptomatic changes in hippocampal physiology in FAD suggest that hippocampal fMRI patterns during associative encoding may also provide a preclinical biomarker in sporadic AD. PMID:21194156

  6. The toxic influence of paraquat on hippocampal neurogenesis in adult mice.

    Science.gov (United States)

    Li, Kaikai; Cheng, Xinran; Jiang, Jinhua; Wang, Jiutao; Xie, Jiongfang; Hu, Xinde; Huang, Yingxue; Song, Lingzhen; Liu, Mengmeng; Cai, Leiming; Chen, Liezhong; Zhao, Shanting

    2017-08-01

    Paraquat, a fast-acting non-selective contact herbicide, is considered an etiological factor related to Parkinson's disease. This study investigated its effects on hippocampal neurogenesis and cognition in adult mice as well as possible mechanisms for the effects. We administered paraquat (1.25 mg/kg, intraperitoneal injection, i.p.) and an equal volume of normal saline for 3 weeks to adult male C57BL/6J mice. The results showed that hippocampus-dependent spatial learning and memory was significantly impaired in paraquat-treated mice. Moreover, paraquat administration inhibited the proliferation of neural progenitor cells, and impaired the survival and altered the fate decision of newly generated cells in the hippocampus. The expression levels of caspase-3 and glial fibrillary acidic protein were significantly higher in paraquat-treated mice than in control mice. Interestingly, paraquat reduced the phosphorylation of Akt, but did not affect the total amount of Akt. In conclusion, our findings suggest that paraquat negatively affected adult hippocampal neurogenesis and cognition function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Resting-state functional connectivity bias of middle temporal gyrus and caudate with altered gray matter volume in major depression.

    Directory of Open Access Journals (Sweden)

    Chaoqiong Ma

    Full Text Available Magnetic resonance imaging (MRI studies have indicated that the structure deficits and resting-state functional connectivity (FC imbalances in cortico-limbic circuitry might underline the pathophysiology of MDD. Using structure and functional MRI, our aim is to investigate gray matter abnormalities in patients with treatment-resistant depression (TRD and treatment-responsive depression (TSD, and test whether the altered gray matter is associated with altered FC. Voxel-based morphometry was used to investigate the regions with gray matter abnormality and FC analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain. Using one-way analysis of variance, we found significant gray matter abnormalities in the right middle temporal cortex (MTG and bilateral caudate among the TRD, TSD and healthy controls. For the FC of the right MTG, we found that both the patients with TRD and TSD showed altered connectivity mainly in the default-mode network (DMN. For the FC of the right caudate, both patient groups showed altered connectivity in the frontal regions. Our results revealed the gray matter reduction of right MTG and bilateral caudate, and disrupted functional connection to widely distributed circuitry in DMN and frontal regions, respectively. These results suggest that the abnormal DMN and reward circuit activity might be biomarkers of depression trait.

  8. Hippocampal-thalamic wiring in medial temporal lobe epilepsy: Enhanced connectivity per hippocampal voxel.

    Science.gov (United States)

    Dinkelacker, Vera; Valabregue, Romain; Thivard, Lionel; Lehéricy, Stéphane; Baulac, Michel; Samson, Séverine; Dupont, Sophie

    2015-08-01

    Medial temporal lobe epilepsy (TLE) with hippocampal sclerosis is often accompanied by widespread changes in ipsilateral and contralateral white matter connectivity. Recent studies have proposed that patients may show pathologically enhanced wiring of the limbic circuits. To better address this issue, we specifically probed connection patterns between hippocampus and thalamus and examined their impact on cognitive function. A group of 44 patients with TLE (22 with right and 22 with left hippocampal sclerosis) and 24 healthy control participants were examined with high-resolution T1 imaging, memory functional magnetic resonance imaging (fMRI) and probabilistic diffusion tractography. Thirty-four patients had further extensive neuropsychological testing. After whole brain segmentation with FreeSurfer, tractography streamline samples were drawn with hippocampus as the seed and thalamus as the target region. Two tractography strategies were applied: The first targeted the anatomic thalamic volume segmented in FreeSurfer and the second a functional region of interest in the mediodorsal thalamus derived from the activation during delayed recognition memory. We found a pronounced enhancement of connectivity between the sclerotic hippocampus and the ipsilateral thalamus both in the right and left TLE as compared to healthy control participants. This finding held for both the anatomically and the functionally defined thalamic target. Although differences were apparent in the number of absolute fibers, they were most pronounced when correcting for hippocampal volume. In terms of cognitive function, the number of hippocampal-thalamic connections was negatively correlated with performance in a variety of executive tasks, notably in the Trail Making Test, thus suggesting that the pathologic wiring did not compensate cognitive curtailing. We suggest that TLE is accompanied by an abnormal and dysfunctional enhancement of connectivity between the hippocampus and the thalamus

  9. Smaller Dentate Gyrus and CA2 and CA3 Volumes Are Associated with Kynurenine Metabolites in Collegiate Football Athletes.

    Science.gov (United States)

    Meier, Timothy B; Savitz, Jonathan; Singh, Rashmi; Teague, T Kent; Bellgowan, Patrick S F

    2016-07-15

    An imbalance in kynurenine pathway metabolism is hypothesized to be associated with dysregulated glutamatergic neurotransmission, which has been proposed as a mechanism underlying the hippocampal volume loss observed in a variety of neurological disorders. Pre-clinical models suggest that the CA2-3 and dentate gyrus hippocampal subfields are particularly susceptible to excitotoxicity after experimental traumatic brain injury. We tested the hypothesis that smaller hippocampal volumes in collegiate football athletes with (n = 25) and without (n = 24) a concussion history would be most evident in the dentate gyrus and CA2-3 subfields relative to nonfootball healthy controls (n = 27). Further, we investigated whether the concentration of peripheral levels of kynurenine metabolites are altered in football athletes. Football athletes with and without a self-reported concussion history had smaller dentate gyrus (p Football athletes with and without a concussion history had a trend toward lower (p football athletes with a concussion history (p football athletes without a concussion history (p < 0.05). Our results raise the possibility that abnormalities of the kynurenine metabolic pathway constitute a mechanism for hippocampal volume differences in the context of sports-related brain injury.

  10. Alterations in right posterior hippocampus in early blind individuals

    DEFF Research Database (Denmark)

    Chebat, Daniel-Robert; Chen, Jan-Kai; Schneider, Fabien

    2007-01-01

    This study compares hippocampal volumes of early blind and sex/age-matched sighted controls through volumetric and localization analyses. Early blind individuals showed a significantly smaller right posterior hippocampus compared with controls. No differences in total hippocampal volumes were found...... between groups and there were no within-group differences for left versus right hippocampus. Sex, age and total brain grey matter volume had no effect on hippocampal volumes. Although extensive navigational training results in structural enhancement of the hippocampus for the sighted, the reduction...... of the posterior hippocampus in early blind individuals suggests the implication of this region in visual spatial memory. Udgivelsesdato: 2007-Mar-5...

  11. Amyloid Beta Peptide Slows Down Sensory-Induced Hippocampal Oscillations

    Directory of Open Access Journals (Sweden)

    Fernando Peña-Ortega

    2012-01-01

    Full Text Available Alzheimer’s disease (AD progresses with a deterioration of hippocampal function that is likely induced by amyloid beta (Aβ oligomers. Hippocampal function is strongly dependent on theta rhythm, and disruptions in this rhythm have been related to the reduction of cognitive performance in AD. Accordingly, both AD patients and AD-transgenic mice show an increase in theta rhythm at rest but a reduction in cognitive-induced theta rhythm. We have previously found that monomers of the short sequence of Aβ (peptide 25–35 reduce sensory-induced theta oscillations. However, considering on the one hand that different Aβ sequences differentially affect hippocampal oscillations and on the other hand that Aβ oligomers seem to be responsible for the cognitive decline observed in AD, here we aimed to explore the effect of Aβ oligomers on sensory-induced theta rhythm. Our results show that intracisternal injection of Aβ1–42 oligomers, which has no significant effect on spontaneous hippocampal activity, disrupts the induction of theta rhythm upon sensory stimulation. Instead of increasing the power in the theta band, the hippocampus of Aβ-treated animals responds to sensory stimulation (tail pinch with an increase in lower frequencies. These findings demonstrate that Aβ alters induced theta rhythm, providing an in vivo model to test for therapeutic approaches to overcome Aβ-induced hippocampal and cognitive dysfunctions.

  12. Hippocampal activity during the transverse patterning task declines with cognitive competence but not with age

    Directory of Open Access Journals (Sweden)

    Leirer Vera M

    2010-09-01

    Full Text Available Abstract Background The hippocampus is a brain region that is particularly affected by age-related morphological changes. It is generally assumed that a loss in hippocampal volume results in functional deficits that contribute to age-related cognitive decline. In a combined cross-sectional behavioural and magnetoencephalography (MEG study we investigated whether hippocampal-associated neural current flow during a transverse patterning task - which requires learning relational associations between stimuli - correlates with age and whether it is modulated by cognitive competence. Results Better performance in several tests of verbal memory, verbal fluency and executive function was indeed associated with higher hippocampal neural activity. Age, however, was not related to the strength of hippocampal neural activity: elderly participants responded slower than younger individuals but on average produced the same neural mass activity. Conclusions Our results suggest that in non-pathological aging, hippocampal neural activity does not decrease with age but is rather related to cognitive competence.

  13. Porencephaly in dogs and cats: relationships between magnetic resonance imaging (MRI) features and hippocampal atrophy.

    Science.gov (United States)

    Hori, Ai; Hanazono, Kiwamu; Miyoshi, Kenjirou; Nakade, Tetsuya

    2015-07-01

    Porencephaly is the congenital cerebral defect and a rare malformation and described few MRI reports in veterinary medicine. MRI features of porencephaly are recognized the coexistence with the unilateral/bilateral hippocampal atrophy, caused by the seizure symptoms in human medicine. We studied 2 dogs and 1 cat with congenital porencephaly to characterize the clinical signs and MRI, and to discuss the associated MRI with hippocampal atrophy. The main clinical sign was the seizure symptoms, and all had hippocampal atrophy at the lesion side or the larger defect side. There is association between hippocampal atrophy or the cyst volume and the severe of clinical signs, and it is suggested that porencephaly coexists with hippocampal atrophy as well as humans in this study.

  14. Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior.

    Science.gov (United States)

    Schaufler, Jörg; Ronovsky, Marianne; Savalli, Giorgia; Cabatic, Maureen; Sartori, Simone B; Singewald, Nicolas; Pollak, Daniela D

    2016-01-01

    Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs - also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated. The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety-related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB). The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment. The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed.

  15. Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis ?

    Directory of Open Access Journals (Sweden)

    Damien eBonhomme

    2014-02-01

    Full Text Available A disruption of the vitamin A signaling pathway has been involved in age-related memory decline and hippocampal plasticity alterations. Using vitamin A deficiency (VAD, a nutritional model leading to a hyposignaling of the retinoid pathway, we have recently demonstrated that retinoic acid (RA, the active metabolite of vitamin A, is efficient to reverse VAD-induced spatial memory deficits and adult hippocampal neurogenesis alterations. Besides, excess of glucocorticoids (GCs occurring with aging is known to strongly inhibit hippocampal plasticity and functions and few studies report on the counteracting effects of RA signaling pathway on GCs action. Here, we have addressed whether the modulation of brain GCs availability could be one of the biological mechanisms involved in the effects of vitamin A status on hippocampal plasticity and functions. Thus, we have studied the effects of a vitamin A-free diet for 14 weeks and a 4-week vitamin A supplementation on plasma and hippocampal corticosterone (CORT levels in Wistar rats. We have also investigated corticosteroid binding globulin (CBG binding capacity and 11beta-Hydrosteroid Dehydrogenase type 1 (11β-HSD1 activity, both important modulators of CORT availability at the peripheral and hippocampal levels respectively. Interestingly, we show that the vitamin A status regulates levels of free plasma CORT and hippocampal CORT levels, by acting through a regulation of CBG binding capacity and 11β-HSD1 activity. Moreover, our results suggest that increased CORT levels in VAD rats could have some deleterious consequences on spatial memory, anxiety-like behavior and adult hippocampal neurogenesis whereas these effects could be corrected by a vitamin A supplementation. Thus, the modulation of GCs availability by vitamin A status is an important biological mechanism that should be taken into account in order to prevent age-related cognitive decline and hippocampal plasticity alterations.

  16. Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis?

    Science.gov (United States)

    Bonhomme, Damien; Minni, Amandine M; Alfos, Serge; Roux, Pascale; Richard, Emmanuel; Higueret, Paul; Moisan, Marie-Pierre; Pallet, Véronique; Touyarot, Katia

    2014-01-01

    A disruption of the vitamin A signaling pathway has been involved in age-related memory decline and hippocampal plasticity alterations. Using vitamin A deficiency (VAD), a nutritional model leading to a hyposignaling of the retinoid pathway, we have recently demonstrated that retinoic acid (RA), the active metabolite of vitamin A, is efficient to reverse VAD-induced spatial memory deficits and adult hippocampal neurogenesis alterations. Besides, excess of glucocorticoids (GCs) occurring with aging is known to strongly inhibit hippocampal plasticity and functions and few studies report on the counteracting effects of RA signaling pathway on GCs action. Here, we have addressed whether the modulation of brain GCs availability could be one of the biological mechanisms involved in the effects of vitamin A status on hippocampal plasticity and functions. Thus, we have studied the effects of a vitamin A-free diet for 14 weeks and a 4-week vitamin A supplementation on plasma and hippocampal corticosterone (CORT) levels in Wistar rats. We have also investigated corticosteroid binding globulin (CBG) binding capacity and 11beta-Hydrosteroid Dehydrogenase type 1 (11β-HSD1) activity, both important modulators of CORT availability at the peripheral and hippocampal levels respectively. Interestingly, we show that the vitamin A status regulates levels of free plasma CORT and hippocampal CORT levels, by acting through a regulation of CBG binding capacity and 11β-HSD1 activity. Moreover, our results suggest that increased CORT levels in VAD rats could have some deleterious consequences on spatial memory, anxiety-like behavior and adult hippocampal neurogenesis whereas these effects could be corrected by a vitamin A supplementation. Thus, the modulation of GCs availability by vitamin A status is an important biological mechanism that should be taken into account in order to prevent age-related cognitive decline and hippocampal plasticity alterations.

  17. Hippocampal insulin resistance links maternal obesity with impaired neuronal plasticity in adult offspring.

    Science.gov (United States)

    Schmitz, Lisa; Kuglin, Rebecca; Bae-Gartz, Inga; Janoschek, Ruth; Appel, Sarah; Mesaros, Andrea; Jakovcevski, Igor; Vohlen, Christina; Handwerk, Marion; Ensenauer, Regina; Dötsch, Jörg; Hucklenbruch-Rother, Eva

    2017-12-28

    Maternal obesity and a disturbed metabolic environment during pregnancy and lactation have been shown to result in many long-term health consequences for the offspring. Among them, impairments in neurocognitive development and performance belong to the most dreaded ones. So far, very few mechanistic approaches have aimed to determine the responsible molecular events. In a mouse model of maternal diet-induced obesity and perinatal hyperinsulinemia, we assessed adult offspring's hippocampal insulin signaling as well as concurrent effects on markers of hippocampal neurogenesis, synaptic plasticity and function using western blotting and immunohistochemistry. In search for a potential link between neuronal insulin resistance and hippocampal plasticity, we additionally quantified protein expression of key molecules of synaptic plasticity in an in vitro model of acute neuronal insulin resistance. Maternal obesity and perinatal hyperinsulinemia result in adult hippocampal insulin resistance with subsequently reduced hippocampal mTor signaling and altered expression of markers of neurogenesis (doublecortin), synaptic plasticity (FoxO1, pSynapsin) and function (vGlut, vGAT) in the offspring. The observed effects are independent of the offspring's adult metabolic phenotype and can be associated with multiple previously reported behavioral abnormalities. Additionally, we demonstrate that induction of insulin resistance in cultured hippocampal neurons reduces mTor signaling, doublecortin and vGAT protein expression. Hippocampal insulin resistance might play a key role in mediating the long-term effects of maternal obesity and perinatal hyperinsulinemia on hippocampal plasticity and the offspring's neurocognitive outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The alteration of gray matter volume in children with mental retardation: the differences between the patients presented with operation deficit predominantly and those presented with language deficit mainly

    International Nuclear Information System (INIS)

    Yuan Xinyu; Jiang Xuexiang; Jin Chunhua; Zhang Yuanchao; Bai Zhenhua; Yi Xiaoli; Xiao Jiangxi

    2012-01-01

    Objective: To detect the differences of grey matter volume between the patients with mental retardation (MR) presented clinically as operation deficit (OD) or as language deficit (LD) and the children with typical normal development using optimal VBM. The developmental connections between brain gray matter and language or operation skills were examined. Methods: Magnetic resonance imaging was obtained from 9 children with mental retardation presented as OD predominantly and 11 children with mental retardation presented as LD mainly, as well as the age-matched control group (11 and 14 normal children,respectively) on a 1.5 T scanner. Voxel-based morphometry analysis with an optimization of spatial segmentation and normalization procedures was applied to compare the volume of grey matter between the two groups (OD VS.control; LD VS.control). Statistically, the total and local gray matter volumes were compared between the two groups with t test. Results: The total gray matter volume of OD group was [(1.030 ± 0.078) × 10 6 mm 3 ]. Compared to that of controls [(0.984 ± 0.058) × 10 6 mm 3 ], it was increased significantly (t=-2.6, P<0.05). And the gray matter volume in the posterior cingulated gyrus, left superior prefrontal gyrus, left cuneus, left middle prefrontal gyrus and the body of left caudate nucleus showed significantly increased. Meanwhile, the total gray matter volume of the MR children presented as LD [(1.002 ± 0.068) × 10 6 mm 3 ] showed significantly increased(t=-3.0, P<0.05) compared with that of control group [(0.957 ±0.057) × 10 6 mm 3 ]. The gray matter volume in bilateral thalami, the left inferior temporal gyrus,the left inferior frontal gyrus, and the left cerebellum of the LD group was more than that of normal children. Conclusion: As revealed by VBM, there are differences in alterations of gray matter volume between MR children presented with OD and with LD relative to control. (authors)

  19. Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI

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    Anna E. Blanken

    2017-01-01

    Full Text Available Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD and 7 cognitively normal (NC subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aβ, tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aβ, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP.

  20. Hummingbirds have a greatly enlarged hippocampal formation.

    Science.gov (United States)

    Ward, Brian J; Day, Lainy B; Wilkening, Steven R; Wylie, Douglas R; Saucier, Deborah M; Iwaniuk, Andrew N

    2012-08-23

    Both field and laboratory studies demonstrate that hummingbirds (Apodiformes, Trochilidae) have exceptional spatial memory. The complexity of spatial-temporal information that hummingbirds must retain and use daily is probably subserved by the hippocampal formation (HF), and therefore, hummingbirds should have a greatly expanded HF. Here, we compare the relative size of the HF in several hummingbird species with that of other birds. Our analyses reveal that the HF in hummingbirds is significantly larger, relative to telencephalic volume, than any bird examined to date. When expressed as a percentage of telencephalic volume, the hummingbird HF is two to five times larger than that of caching and non-caching songbirds, seabirds and woodpeckers. This HF expansion in hummingbirds probably underlies their ability to remember the location, distribution and nectar content of flowers, but more detailed analyses are required to determine the extent to which this arises from an expansion of HF or a decrease in size of other brain regions.

  1. Optimizing patient positioning for intensity modulated radiation therapy in hippocampal-sparing whole brain radiation therapy.

    Science.gov (United States)

    Siglin, Joshua; Champ, Colin E; Vakhnenko, Yelena; Witek, Matthew E; Peng, Cheng; Zaorsky, Nicholas G; Harrison, Amy S; Shi, Wenyin

    2014-01-01

    Sparing the hippocampus during whole brain radiation therapy (WBRT) offers potential neurocognitive benefits. However, previously reported intensity modulated radiation therapy (IMRT) plans use multiple noncoplanar beams for treatment delivery. An optimized coplanar IMRT template for hippocampal-sparing WBRT would assist in clinical workflow and minimize resource utilization. In this study, we sought to determine the optimal patient position to facilitate coplanar treatment planning and delivery of hippocampal-sparing WBRT using IMRT. A variable angle, inclined board was utilized for patient positioning. An anthropomorphic phantom underwent computed tomography simulation at various head angles. The IMRT goals were designed to achieve target coverage of the brain while maintaining hippocampal dose-volume constraints designed to conform to the Radiation Therapy Oncology Group 0933 protocol. Optimal head angle was then verified using data from 8 patients comparing coplanar and noncoplanar WBRT IMRT plans. Hippocampal, hippocampal avoidance region, and whole brain mean volumes were 1.1 cm(3), 12.5 cm(3), and 1185.1 cm(3), respectively. The hippocampal avoidance region occupied 1.1% of the whole brain planning volume. For the 30-degree head angle, a 7-field coplanar IMRT plan was generated, sparing the hippocampus to a maximum dose of 14.7 Gy; D100% of the hippocampus was 7.4 Gy and mean hippocampal dose was 9.3 Gy. In comparison, for flat head positioning the hippocampal Dmax was 22.9 Gy with a D100% of 9.2 Gy and mean dose of 11.7 Gy. Target coverage and dose homogeneity was comparable with previously published noncoplanar IMRT plans. Compared with conventional supine positioning, an inclined head board at 30 degrees optimizes coplanar whole brain IMRT treatment planning. Clinically acceptable hippocampal-sparing WBRT dosimetry can be obtained using a simplified coplanar plan at a 30-degree head angle, thus obviating the need for complex and time consuming noncoplanar

  2. Protracted hippocampal development is associated with age-related improvements in memory during early childhood.

    Science.gov (United States)

    Riggins, Tracy; Geng, Fengji; Botdorf, Morgan; Canada, Kelsey; Cox, Lisa; Hancock, Gregory R

    2018-03-05

    The hippocampus is a structure that is critical for memory. Previous studies have shown that age-related differences in specialization along the longitudinal axis of this structure (i.e., subregions) and within its internal circuitry (i.e., subfields) relate to age-related improvements in memory in school-age children and adults. However, the influence of age on hippocampal development and its relations with memory ability earlier in life remains under-investigated. This study examined effects of age and sex on hippocampal subregion (i.e., head, body, tail) and subfield (i.e., subiculum, CA1, CA2-4/DG) volumes, and their relations with memory, using a large sample of 4- to 8-year-old children. Results examining hippocampal subregions suggest influences of both age and sex on the hippocampal head during early childhood. Results examining subfields within hippocampal head suggest these age effects may arise from CA1, whereas sex differences may arise from subiculum and CA2-4/DG. Memory ability was not associated with hippocampal subregion volume but was associated with subfield volume. Specifically, within the hippocampal head, relations between memory and CA1 were moderated by age; in younger children bigger was better, whereas in older children smaller was superior. Within the hippocampal body, smaller CA1 and larger CA2-4/DG contributed to better memory performance across all ages. Together, these results shed light on hippocampal development during early childhood and support claims that the prolonged developmental trajectory of the hippocampus contributes to memory development early in life. Copyright © 2018. Published by Elsevier Inc.

  3. Hippocampal volumes in patients exposed to low-dose radiation to the basal brain : a case–control study in long-term survivors from cancer in the head and neck region

    OpenAIRE

    Olsson, Erik; Eckerström, Carl; Berg, Gertrud; Borga, Magnus; Ekholm, Sven; Johannsson, Gudmundur; Ribbelin, Susanne; Starck, Görgan; Wysocka, Anna; Löfdahl, Elisabet; Malmgren, Helge

    2012-01-01

    Abstract Background An earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients’ lowered QoL was coupled to a reduc...

  4. Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry.

    Science.gov (United States)

    Joo, Eun Yeon; Kim, Hosung; Suh, Sooyeon; Hong, Seung Bong

    2014-07-01

    Despite compelling evidence from animal studies indicating hippocampal subfield-specific vulnerability to poor sleep quality and related cognitive impairment, there have been no human magnetic resonance imaging (MRI) studies investigating the relationship between hippocampal subfield volume and sleep disturbance. Our aim was to investigate the pattern of volume changes across hippocampal subfields in patients with primary insomnia relative to controls. Pointwise morphometry allowed for volume measurements of hippocampal regions on T1-weighted MRI. University hospital. Twenty-seven unmedicated patients (age: 51.2 ± 9.6 y) and 30 good sleepers as controls (50.4 ± 7.1 y). N/A. We compared hippocampal subfield volumes between patients and controls and correlated volume with clinical and neuropsychological features in patients. Patients exhibited bilateral atrophy across all hippocampal subfields (P sleep quality (higher Pittsburgh Sleep Quality Index and higher arousal index of polysomnography) (r 0.45, P sleep fragmentation and related chronic stress condition. Atrophy in the CA3-4-DG region was associated with impaired cognitive functions in patients. These observations may provide insight into pathophysiological mechanisms that make patients with chronic sleep disturbance vulnerable to cognitive impairment. Joo EY, Kim H, Suh S, Hong SB. Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry.

  5. Stress, depression and hippocampal damage

    Indian Academy of Sciences (India)

    adrenocortical (HPA) axis which regulates secretion of the stress responsive corticosteroids. The hippocampus is known to provide an inhibitory feedback to the HPA axis. Hippocampal damage then would result in disinhibition of the HPA axis ...

  6. Early Prediction of Outcome in Advanced Head-and-Neck Cancer Based on Tumor Blood Volume Alterations During Therapy: A Prospective Study

    International Nuclear Information System (INIS)

    Cao Yue; Popovtzer, Aron; Li, Diana; Chepeha, Douglas B.; Moyer, Jeffrey S.; Prince, Mark E.; Worden, Francis; Teknos, Theodoros; Bradford, Carol; Mukherji, Suresh K.; Eisbruch, Avraham

    2008-01-01

    Purpose: To assess whether alterations in tumor blood volume (BV) and blood flow (BF) during the early course of chemo-radiotherapy (chemo-RT) for head-and-neck cancer (HNC) predict treatment outcome. Methods and Materials: Fourteen patients receiving concomitant chemo-RT for nonresectable, locally advanced HNC underwent dynamic contrast-enhanced (DCE) MRI scans before therapy and 2 weeks after initiation of chemo-RT. The BV and BF were quantified from DCE MRI. Preradiotherapy BV and BF, as well as their changes during RT, were evaluated separately in the primary gross tumor volume (GTV) and nodal GTV for association with outcomes. Results: At a median follow-up of 10 months (range, 5-27 months), 9 patients had local-regional controlled disease. One patient had regional failure, 3 had local failures, and 1 had local-regional failure. Reduction in tumor volume after 2 weeks of chemo-RT did not predict for local control. In contrast, the BV in the primary GTV after 2 weeks of chemo-RT was increased significantly in the local control patients compared with the local failure patients (p < 0.03). Conclusions: Our data suggest that an increase in available primary tumor blood for oxygen extraction during the early course of RT is associated with local control, thus yielding a predictor with potential to modify treatment. These findings require validation in larger studies

  7. Hippocampal Atrophy Following Subarachnoid Hemorrhage Correlates with Disruption of Astrocyte Morphology and Capillary Coverage by AQP4

    DEFF Research Database (Denmark)

    Anzabi, Maryam; Ardalan, Maryam; Iversen, Nina Kerting

    2018-01-01

    techniques to detect differences in astrocyte morphology, and global spatial sampling method was used to quantify the length density of Aquaporin-4 (AQP4) positive capillaries. Our results indicated that hippocampal volume, as measured both by MRI and by histological approaches, was significantly lower...... in SAH animals than in the sham-operated group. Accordingly, in this animal model of SAH, hippocampal atrophy existed already at the time of DCI onset in humans. SAH induced retraction of GFAP positive astrocyte processes, accompanied by a significant reduction in the length density of AQP4 positive...... capillaries as well as narrowing of hippocampal capillaries. Meanwhile, astrocyte volume was higher in SAH mice compared with the sham-operated group. Morphological changes in hippocampal astrocytes seemingly disrupt glia-vascular interactions early after SAH and may contribute to hippocampal atrophy. We...

  8. Lower Ipsilateral Hippocampal Integrity after Ischemic Stroke in Young Adults: A Long-Term Follow-Up Study

    NARCIS (Netherlands)

    Schaapsmeerders, P.; Tuladhar, A.M.; Maaijwee, N.A.M.M.; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Dijk, E.J. van; Kessels, R.P.C.; Leeuw, H.F. de

    2015-01-01

    Background and purpose Memory impairment after stroke is poorly understood as stroke rarely occurs in the hippocampus. Previous studies have observed smaller ipsilateral hippocampal volumes after stroke compared with controls. Possibly, these findings on macroscopic level are not the first

  9. Lower Ipsilateral Hippocampal Integrity after Ischemic Stroke in Young Adults: A Long-Term Follow-Up Study

    NARCIS (Netherlands)

    Schaapsmeerders, P.; Tuladhar, A.M.; Maaijwee, N.A.M.M.; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.; Dijk, E.J. van; Kessels, R.P.C.; Leeuw, F.E. de

    2015-01-01

    BACKGROUND AND PURPOSE: Memory impairment after stroke is poorly understood as stroke rarely occurs in the hippocampus. Previous studies have observed smaller ipsilateral hippocampal volumes after stroke compared with controls. Possibly, these findings on macroscopic level are not the first

  10. Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults

    NARCIS (Netherlands)

    Schaapsmeerders, P.; Uden, I.W.M. van; Tuladhar, A.M.; Maaijwee, N.A.M.M.; Dijk, E.J. van; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Leeuw, H.F. de; Kessels, R.P.C.

    2015-01-01

    Memory impairment after stroke in young adults is poorly understood. In elderly stroke survivors memory impairments and the concomitant loss of hippocampal volume are usually explained by coexisting neurodegenerative disease (e.g., amyloid pathology) in interaction with stroke. However,

  11. Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis.

    Science.gov (United States)

    Wise, T; Radua, J; Via, E; Cardoner, N; Abe, O; Adams, T M; Amico, F; Cheng, Y; Cole, J H; de Azevedo Marques Périco, C; Dickstein, D P; Farrow, T F D; Frodl, T; Wagner, G; Gotlib, I H; Gruber, O; Ham, B J; Job, D E; Kempton, M J; Kim, M J; Koolschijn, P C M P; Malhi, G S; Mataix-Cols, D; McIntosh, A M; Nugent, A C; O'Brien, J T; Pezzoli, S; Phillips, M L; Sachdev, P S; Salvadore, G; Selvaraj, S; Stanfield, A C; Thomas, A J; van Tol, M J; van der Wee, N J A; Veltman, D J; Young, A H; Fu, C H; Cleare, A J; Arnone, D

    2017-10-01

    Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

  12. Stress and adolescent hippocampal neurogenesis: diet and exercise as cognitive modulators.

    Science.gov (United States)

    Hueston, C M; Cryan, J F; Nolan, Y M

    2017-04-04

    Adolescence is a critical period for brain maturation. Deciphering how disturbances to the central nervous system at this time affect structure, function and behavioural outputs is important to better understand any long-lasting effects. Hippocampal neurogenesis occurs during development and continues throughout life. In adulthood, integration of these new cells into the hippocampus is important for emotional behaviour, cognitive function and neural plasticity. During the adolescent period, maturation of the hippocampus and heightened levels of hippocampal neurogenesis are observed, making alterations to neurogenesis at this time particularly consequential. As stress negatively affects hippocampal neurogenesis, and adolescence is a particularly stressful time of life, it is important to investigate the impact of stressor exposure at this time on hippocampal neurogenesis and cognitive function. Adolescence may represent not only a time for which stress can have long-lasting effects, but is also a critical period during which interventions, such as exercise and diet, could ameliorate stress-induced changes to hippocampal function. In addition, intervention at this time may also promote life-long behavioural changes that would aid in fostering increased hippocampal neurogenesis and cognitive function. This review addresses both the acute and long-term stress-induced alterations to hippocampal neurogenesis and cognition during the adolescent period, as well as changes to the stress response and pubertal hormones at this time which may result in differential effects than are observed in adulthood. We hypothesise that adolescence may represent an optimal time for healthy lifestyle changes to have a positive and long-lasting impact on hippocampal neurogenesis, and to protect against stress-induced deficits. We conclude that future research into the mechanisms underlying the susceptibility of the adolescent hippocampus to stress, exercise and diet and the consequent effect

  13. Age-dependent alterations in the number, volume, and localization of islands of Calleja within the olfactory tubercle.

    Science.gov (United States)

    Adjei, Stacey; Houck, Alexandra L; Ma, Katherine; Wesson, Daniel W

    2013-11-01

    The incidence of olfactory perceptual dysfunction increases substantially with aging. Putative mechanisms for olfactory sensory loss are surfacing, including neuroanatomical modifications within brain regions responsible for odor information processing. The islands of Calleja (IC) are dense cell clusters localized within the olfactory tubercle, a cortical structure receiving monosynaptic input from the olfactory bulb. The IC are hypothesized to be important for intra- and extra-olfactory tubercle information processing, and thus olfaction. However, whether the anatomy of the IC are affected throughout normal aging remains unclear. By examining the IC of C57bl/6 mice throughout adulthood and early aging (4-18 months of age), we found that the number of IC decreases significantly with aging. Stereological analysis revealed that the remaining IC in 18-month-old mice were significantly reduced in estimated volume compared with those in 4- month-old mice. We additionally found that whereas young adults (4 months of age) possess greater numbers of IC within the posterior parts of the olfactory tubercle, by 18 months of age, a greater percentage of IC are found within the anterior-most part of the olfactory tubercle, perhaps providing a substrate for the differential access of the IC to odor information throughout aging. These results show that the IC are highly plastic components of the olfactory cortex, changing in volume, localization, and even number throughout normal aging. We predict that modifications among the IC throughout aging and age-related neurodegenerative disorders might be a novel contributor to pathological changes in olfactory cortex function and olfactory perception. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Food restriction reduces neurogenesis in the avian hippocampal formation.

    Directory of Open Access Journals (Sweden)

    Barbara-Anne Robertson

    Full Text Available The mammalian hippocampus is particularly vulnerable to chronic stress. Adult neurogenesis in the dentate gyrus is suppressed by chronic stress and by administration of glucocorticoid hormones. Post-natal and adult neurogenesis are present in the avian hippocampal formation as well, but much less is known about its sensitivity to chronic stressors. In this study, we investigate this question in a commercial bird model: the broiler breeder chicken. Commercial broiler breeders are food restricted during development to manipulate their growth curve and to avoid negative health outcomes, including obesity and poor reproductive performance. Beyond knowing that these chickens are healthier than fully-fed birds and that they have a high motivation to eat, little is known about how food restriction impacts the animals' physiology. Chickens were kept on a commercial food-restricted diet during the first 12 weeks of life, or released from this restriction by feeding them ad libitum from weeks 7-12 of life. To test the hypothesis that chronic food restriction decreases the production of new neurons (neurogenesis in the hippocampal formation, the cell proliferation marker bromodeoxyuridine was injected one week prior to tissue collection. Corticosterone levels in blood plasma were elevated during food restriction, even though molecular markers of hypothalamic-pituitary-adrenal axis activation did not differ between the treatments. The density of new hippocampal neurons was significantly reduced in the food-restricted condition, as compared to chickens fed ad libitum, similar to findings in rats at a similar developmental stage. Food restriction did not affect hippocampal volume or the total number of neurons. These findings indicate that in birds, like in mammals, reduction in hippocampal neurogenesis is associated with chronically elevated corticosterone levels, and therefore potentially with chronic stress in general. This finding is consistent with the

  15. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

    Science.gov (United States)

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-06-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

  16. Distinguishing Depressive Pseudodementia from Alzheimer Disease: A Comparative Study of Hippocampal Volumetry and Cognitive Tests

    Directory of Open Access Journals (Sweden)

    Sevki Sahin

    2017-07-01

    Full Text Available Background and Aim: Depressive pseudodementia (DPD is a condition which may develop secondary to depression. The aim of this study was to contribute to the differential diagnosis between Alzheimer disease (AD and DPD by comparing the neurocognitive tests and hippocampal volume. Materials and Methods: Patients who met criteria of AD/DPD were enrolled in the study. All patients were assessed using the Wechsler Memory Scale (WMS, clock-drawing test, Stroop test, Benton Facial Recognition Test (BFRT, Boston Naming Test, Mini-Mental State Examination (MMSE, and Geriatric Depression Scale (GDS. Hippocampal volume was measured by importing the coronal T1-weighted magnetic resonance images to the Vitrea 2 workstation. Results: A significant difference was found between the AD and DPD groups on the WMS test, clock-drawing test, Stroop test, Boston Naming Test, MMSE, GDS, and left hippocampal volume. A significant correlation between BFRT and bilateral hippocampal volumes was found in the AD group. No correlation was found among parameters in DPD patients. Conclusions: Our results suggest that evaluation of facial recognition and left hippocampal volume may provide more reliable evidence for distinguishing DPD from AD. Further investigations combined with functional imaging techniques including more patients are needed.

  17. Hippocampal harms, protection and recovery following regular cannabis use

    Science.gov (United States)

    Yücel, M; Lorenzetti, V; Suo, C; Zalesky, A; Fornito, A; Takagi, M J; Lubman, D I; Solowij, N

    2016-01-01

    Shifting policies towards legalisation of cannabis for therapeutic and recreational use raise significant ethical issues for health-care providers seeking evidence-based recommendations. We investigated whether heavy cannabis use is associated with persistent harms to the hippocampus, if exposure to cannabidiol offers protection, and whether recovery occurs with abstinence. To do this, we assessed 111 participants: 74 long-term regular cannabis users (with an average of 15.4 years of use) and 37 non-user healthy controls. Cannabis users included subgroups of participants who were either exposed to Δ9-tetrahydrocannabinol (THC) but not to cannabidiol (CBD) or exposed to both, and former users with sustained abstinence. Participants underwent magnetic resonance imaging from which three measures of hippocampal integrity were assessed: (i) volume; (ii) fractional anisotropy; and (iii) N-acetylaspartate (NAA). Three curve-fitting models across the entire sample were tested for each measure to examine whether cannabis-related hippocampal harms are persistent, can be minimised (protected) by exposure to CBD or recovered through long-term abstinence. These analyses supported a protection and recovery model for hippocampal volume (P=0.003) and NAA (P=0.001). Further pairwise analyses showed that cannabis users had smaller hippocampal volumes relative to controls. Users not exposed to CBD had 11% reduced volumes and 15% lower NAA concentrations. Users exposed to CBD and former users did not differ from controls on any measure. Ongoing cannabis use is associated with harms to brain health, underpinned by chronic exposure to THC. However, such harms are minimised by CBD, and can be recovered with extended periods of abstinence. PMID:26756903

  18. BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume

    DEFF Research Database (Denmark)

    Martin, Nellie Anne; Bonner, Helena; Elkjær, Maria Louise

    2016-01-01

    The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID...... deficiency protected organotypic hippocampal slice cultures in vitro from neuronal injury induced by oxygen-glucose deprivation. In vivo, BID-knockout (KO) mice and wild type (WT) mice were subjected to 60 min of transient middle cerebral artery occlusion (tMCAO) to induce focal cerebral ischemia...... between BID-KO and WT mice. The inflammatory response was reduced by BID deficiency as indicated by a change in microglial/leukocyte response. In conclusion, our data suggest that BID deficiency is neuroprotective in an in vitro model and modulates the inflammatory response to focal cerebral ischemia...

  19. Hippocampal development in youth with a history of childhood maltreatment.

    Science.gov (United States)

    Paquola, Casey; Bennett, Maxwell R; Hatton, Sean N; Hermens, Daniel F; Groote, Inge; Lagopoulos, Jim

    2017-08-01

    Childhood maltreatment (CM) is associated with enhanced risk of psychiatric illness and reduced subcortical grey matter in adulthood. The hippocampus and amygdala, due to their involvement in stress and emotion circuitries, have been subject to extensive investigations regarding the effect of CM. However, the complex relationship between CM, subcortical grey matter and mental illness remains poorly understood partially due to a lack of longitudinal studies. Here we used segmentation and linear mixed effect modelling to examine the impact of CM on hippocampal and amygdala development in young people with emerging mental illness. A total of 215 structural magnetic resonance imaging (MRI) scans were acquired from 123 individuals (age: 14-28 years, 79 female), 52 of whom were scanned twice or more. Hippocampal and amygdala volumes increased linearly with age, and their developmental trajectories were not moderated by symptom severity. However, exposure to CM was associated with significantly stunted right hippocampal growth. This finding bridges the gap between child and adult research in the field and provides novel evidence that CM is associated with disrupted hippocampal development in youth. Although CM was associated with worse symptom severity, we did not find evidence that CM-induced structural abnormalities directly underpin psychopathology. This study has important implications for the psychiatric treatment of individuals with CM since they are clinically and neurobiologically distinct from their peers who were not maltreated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y [University of Michigan, Ann Arbor, MI (United States)

    2014-06-15

    Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

  1. Environmental Novelty is Associated with a Selective Increase in Fos Expression in the Output Elements of the Hippocampal Formation and the Perirhinal Cortex

    Science.gov (United States)

    VanElzakker, Michael; Fevurly, Rebecca D.; Breindel, Tressa; Spencer, Robert L.

    2008-01-01

    If the hippocampus plays a role in the detection of novel environmental features, then novelty should be associated with altered hippocampal neural activity and perhaps also measures of neuroplasticity. We examined Fos protein expression within subregions of rat hippocampal formation as an indicator of recent increases in neuronal excitation and…

  2. Serotonin dependent masking of hippocampal sharp wave ripples.

    Science.gov (United States)

    ul Haq, Rizwan; Anderson, Marlene L; Hollnagel, Jan-Oliver; Worschech, Franziska; Sherkheli, Muhammad Azahr; Behrens, Christoph J; Heinemann, Uwe

    2016-02-01

    Sharp wave ripples (SPW-Rs) are thought to play an important role in memory consolidation. By rapid replay of previously stored information during slow wave sleep and consummatory behavior, they result from the formation of neural ensembles during a learning period. Serotonin (5-HT), suggested to be able to modify SPW-Rs, can affect many neurons simultaneously by volume transmission and alter network functions in an orchestrated fashion. In acute slices from dorsal hippocampus, SPW-Rs can be induced by repeated high frequency stimulation that induces long-lasting LTP. We used this model to study SPW-R appearance and modulation by 5-HT. Although stimulation in presence of 5-HT permitted LTP induction, SPW-Rs were "masked"--but appeared after 5-HT wash-out. This SPW-R masking was dose dependent with 100 nM 5-HT being sufficient--if the 5-HT re-uptake inhibitor citalopram was present. Fenfluramine, a serotonin releaser, could also mask SPW-Rs. Masking was due to 5-HT1A and 5-HT2A/C receptor activation. Neither membrane potential nor membrane conductance changes in pyramidal cells caused SPW-R blockade since both remained unaffected by combining 5-HT and citalopram. Moreover, 10 and 30 μM 5-HT mediated SPW-R masking preceded neuronal hyperpolarization and involved reduced presynaptic transmitter release. 5-HT, as well as a 5-HT1A agonist, augmented paired pulse facilitation and affected the coefficient of variance. Spontaneous SPW-Rs in mice hippocampal slices were also masked by 5-HT and fenfluramine. While neuronal ensembles can acquire long lasting LTP during higher 5-HT levels, lower 5-HT levels enable neural ensembles to replay previously stored information and thereby permit memory consolidation memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Decreased rhythmic GABAergic septal activity and memory-associated theta oscillations after hippocampal amyloid-beta pathology in the rat.

    Science.gov (United States)

    Villette, Vincent; Poindessous-Jazat, Frédérique; Simon, Axelle; Léna, Clément; Roullot, Elodie; Bellessort, Brice; Epelbaum, Jacques; Dutar, Patrick; Stéphan, Aline

    2010-08-18

    The memory deficits associated with Alzheimer's disease result to a great extent from hippocampal network dysfunction. The coordination of this network relies on theta (symbol) oscillations generated in the medial septum. Here, we investigated in rats the impact of hippocampal amyloid beta (Abeta) injections on the physiological and cognitive functions that depend on the septohippocampal system. Hippocampal Abeta injections progressively impaired behavioral performances, the associated hippocampal theta power, and theta frequency response in a visuospatial recognition test. These alterations were associated with a specific reduction in the firing of the identified rhythmic bursting GABAergic neurons responsible for the propagation of the theta rhythm to the hippocampus, but without loss of medial septal neurons. Such results indicate that hippocampal Abeta treatment leads to a specific functional depression of inhibitory projection neurons of the medial septum, resulting in the functional impairment of the temporal network.

  4. Induction of the Wnt antagonist Dickkopf-1 is involved in stress-induced hippocampal damage.

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    Francesco Matrisciano

    Full Text Available The identification of mechanisms that mediate stress-induced hippocampal damage may shed new light into the pathophysiology of depressive disorders and provide new targets for therapeutic intervention. We focused on the secreted glycoprotein Dickkopf-1 (Dkk-1, an inhibitor of the canonical Wnt pathway, involved in neurodegeneration. Mice exposed to mild restraint stress showed increased hippocampal levels of Dkk-1 and reduced expression of β-catenin, an intracellular protein positively regulated by the canonical Wnt signalling pathway. In adrenalectomized mice, Dkk-1 was induced by corticosterone injection, but not by exposure to stress. Corticosterone also induced Dkk-1 in mouse organotypic hippocampal cultures and primary cultures of hippocampal neurons and, at least in the latter model, the action of corticosterone was reversed by the type-2 glucocorticoid receptor antagonist mifepristone. To examine whether induction of Dkk-1 was causally related to stress-induced hippocampal damage, we used doubleridge mice, which are characterized by a defective induction of Dkk-1. As compared to control mice, doubleridge mice showed a paradoxical increase in basal hippocampal Dkk-1 levels, but no Dkk-1 induction in response to stress. In contrast, stress reduced Dkk-1 levels in doubleridge mice. In control mice, chronic stress induced a reduction in hippocampal volume associated with neuronal loss and dendritic atrophy in the CA1 region, and a reduced neurogenesis in the dentate gyrus. Doubleridge mice were resistant to the detrimental effect of chronic stress and, instead, responded to stress with increases in dendritic arborisation and neurogenesis. Thus, the outcome of chronic stress was tightly related to changes in Dkk-1 expression in the hippocampus. These data indicate that induction of Dkk-1 is causally related to stress-induced hippocampal damage and provide the first evidence that Dkk-1 expression is regulated by corticosteroids in the central

  5. Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.

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    Robert Nisticò

    Full Text Available Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS and its mouse model, experimental autoimmune encephalomyelitis (EAE. In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP induction was favored over long-term depression (LTD in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.

  6. Gestational Exposure to Air Pollution Alters Cortical Volume, Microglial Morphology, and Microglia-Neuron Interactions in a Sex-Specific Manner

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    Jessica L. Bolton

    2017-05-01

    Full Text Available Microglia are the resident immune cells of the brain, important for normal neural development in addition to host defense in response to inflammatory stimuli. Air pollution is one of the most pervasive and harmful environmental toxicants in the modern world, and several large scale epidemiological studies have recently linked prenatal air pollution exposure with an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD. Diesel exhaust particles (DEP are a primary toxic component of air pollution, and markedly activate microglia in vitro and in vivo in adult rodents. We have demonstrated that prenatal exposure to DEP in mice, i.e., to the pregnant dams throughout gestation, results in a persistent vulnerability to behavioral deficits in adult offspring, especially in males, which is intriguing given the greater incidence of ASD in males to females (∼4:1. Moreover, there is a striking upregulation of toll-like receptor (TLR 4 gene expression within the brains of the same mice, and this expression is primarily in microglia. Here we explored the impact of gestational exposure to DEP or vehicle on microglial morphology in the developing brains of male and female mice. DEP exposure increased inflammatory cytokine protein and altered the morphology of microglia, consistent with activation or a delay in maturation, only within the embryonic brains of male mice; and these effects were dependent on TLR4. DEP exposure also increased cortical volume at embryonic day (E18, which switched to decreased volume by post-natal day (P30 in males, suggesting an impact on the developing neural stem cell niche. Consistent with this hypothesis, we found increased microglial-neuronal interactions in male offspring that received DEP compared to all other groups. Taken together, these data suggest a mechanism by which prenatal exposure to environmental toxins may affect microglial development and long-term function, and thereby contribute

  7. Polyphenol-rich extract of Vernonia amygdalina (del. leaves ameliorated cadmium-induced alterations in feeding pattern and urine volume of male Wistar rats.

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    Christian Eseigbe Imafidon

    2015-12-01

    Full Text Available Aim: To determine the effects of polyphenol-rich extract of the leaves of Vernonia amygdalina (PEVA on the feeding pattern of rats that were exposed to cadmium (Cd toxicity. Materials and Methods: Thirty male Wistar rats, weighing 160-180 g, were divided into 6 groups of 5 rats each as follows; Group 1 received distilled water orally (0.2 ml/100 g, daily, throughout the period of study. Group 2 received Cd alone (in the form of CdSO4 at 5 mg/kg/day via intraperitoneal route for 5 consecutive days. Group 3 were pre-treated with Cd as Group 2 and thereafter left untreated for a period of 4-week. After the oral lethal dose of PEVA was determined, Groups 4, 5, and 6 were pre-treated with Cd as Group 2 after which they received graded doses of PEVA at 100, 200 and 400 mg/kg/day (0.2 ml/100 g, respectively via oral route for 4 weeks. Blood samples were collected for some plasma biochemical assays while urine samples were collected using metabolic cages. Results: PEVA administration significantly increased (P < 0.05 the body weight and feeding patterns that were significantly reduced (P < 0.05 by Cd toxicity. PEVA also significantly reinstated the plasma antioxidant status, as well as glucose and urine volume of the rats toward control values (P < 0.05. Conclusion: PEVA can be an herbal alternative in the treatment or management of subjects manifesting alterations in feeding pattern and urine volume that is Cd-induced. [J Intercult Ethnopharmacol 2015; 4(4.000: 284-292

  8. Hippocampal shape is predictive for the development of dementia in a normal, elderly population

    DEFF Research Database (Denmark)

    Achterberg, Hakim C.; van der Lijn, Fedde; den Heijer, Tom

    2014-01-01

    assessed whether hippocampal shape provides additional predictive value independent of hippocampal volume. Five hundred eleven brain MRI scans from elderly nondemented participants of a prospective population-based imaging study were used. During the 10-year follow-up period, 52 of these subjects developed...... dementia. For training and evaluation independent of age and gender, a subset of 50 cases and 150 matched controls was selected. The hippocampus was segmented using an automated method. From the segmentation, the volume was determined and a statistical shape model was constructed. We trained a classifier...

  9. Sleep benefits subsequent hippocampal functioning

    NARCIS (Netherlands)

    van der Werf, Y.D.; Altena, E.; Schoonheim, M.M.; Sanz-Arigita, E.J.; Vis, J.C.; de Rijke, W.; van Someren, E.J.

    2009-01-01

    Sleep before learning benefits memory encoding through unknown mechanisms. We found that even a mild sleep disruption that suppressed slow-wave activity and induced shallow sleep, but did not reduce total sleep time, was sufficient to affect subsequent successful encoding-related hippocampal

  10. Elevation of hippocampal neurogenesis induces a temporally-graded pattern of forgetting of contextual fear memories.

    Science.gov (United States)

    Gao, Aijing; Xia, Frances; Guskjolen, Axel; Ramsaran, Adam I; Santoro, Adam; Josselyn, Sheena A; Frankland, Paul W

    2018-02-16

    Throughout life neurons are continuously generated in the subgranular zone of the hippocampus. The subsequent integration of newly-generated neurons alters patterns of dentate gyrus input and output connectivity, potentially rendering memories already stored in those circuits harder to access. Consistent with this prediction, we previously showed that increasing hippocampal neurogenesis after training induces forgetting of hippocampus-dependent memories, including contextual fear memory. However, the brain regions supporting contextual fear memories change with time, and this time-dependent memory reorganization might regulate the sensitivity of contextual fear memories to fluctuations in hippocampal neurogenesis. By virally expressing the inhibitory DREADD hM4Di we first confirmed that chemogenetic inhibition of dorsal hippocampal neurons impairs retrieval of recent (day-old) but not remote (month-old) contextual fear memories in male mice. We then contrasted the effects of increasing hippocampal neurogenesis at recent vs remote time points after contextual fear conditioning in male and female mice. Increasing hippocampal neurogenesis immediately following training reduced conditioned freezing when mice were replaced in the context one month later. In contrast, when hippocampal neurogenesis was increased time points remote to training, conditioned freezing levels were unaltered when mice were subsequently tested. These temporally-graded forgetting effects were observed using both environmental and genetic interventions to increase hippocampal neurogenesis. Our experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting and suggest that as contextual fear memories mature they become less sensitive to changes in hippocampal neurogenesis levels because they no longer depend on the hippocampus for their expression. Significance statement: New neurons are generated in the hippocampus throughout life. As they integrate into the

  11. The impact of cocaine on adult hippocampal neurogenesis: Potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder.

    Science.gov (United States)

    Castilla-Ortega, Estela; Ladrón de Guevara-Miranda, David; Serrano, Antonia; Pavón, Francisco J; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2017-10-01

    After discovering that addictive drugs alter adult neurogenesis, the potential role of adult-born hippocampal neurons in drug addiction has become a promising research field, in which cocaine is the most frequently investigated drug. Although a substantial amount of pre-clinical evidence has accumulated, additional studies are required to reveal the mechanisms by which cocaine modulates adult hippocampal neurogenesis (AHN) and determine whether these adult-born neurons have a role in cocaine-related behaviors, such as cocaine-mediated cognitive symptoms. First, this review will summarize the cocaine-induced alterations in a number of neurobiological factors (neurotransmitters, neurotrophins, glucocorticoids, inflammatory mediators) that likely regulate both hippocampal-dependent learning and adult hippocampal neurogenesis after cocaine exposure. A separate section will provide a detailed review of the available literature that challenges the common view that cocaine reduces adult hippocampal neurogenesis. In fact, cocaine has a short-term anti-proliferative role, but the young adult-born neurons are apparently spared, or even enhanced, following certain cocaine protocols. Thus, we will try to reconcile this evidence with the hippocampal-dependent cognitive symptoms that are typically observed in cocaine addicts, and we will propose new directions for future studies to test the relevant hypothesis. Based on the evidence presented here, the regulation of adult hippocampal neurogenesis might be one of the many mechanisms by which cocaine sculpts hippocampus-dependent learning. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy

    International Nuclear Information System (INIS)

    Kazda, Tomas; Slampa, Pavel; Laack, Nadia N; Jancalek, Radim; Pospisil, Petr; Sevela, Ondrej; Prochazka, Tomas; Vrzal, Miroslav; Burkon, Petr; Slavik, Marek; Hynkova, Ludmila

    2014-01-01

    The goal of this review is to summarize the rationale for and feasibility of hippocampal sparing techniques during brain irradiation. Radiotherapy is the most effective non-surgical treatment of brain tumors and with the improvement in overall survival for these patients over the last few decades, there is an effort to minimize potential adverse effects leading to possible worsening in quality of life, especially worsening of neurocognitive function. The hippocampus and associated limbic system have long been known to be important in memory formation and pre-clinical models show loss of hippocampal stem cells with radiation as well as changes in architecture and function of mature neurons. Cognitive outcomes in clinical studies are beginning to provide evidence of cognitive effects associated with hippocampal dose and the cognitive benefits of hippocampal sparing. Numerous feasibility planning studies support the feasibility of using modern radiotherapy systems for hippocampal sparing during brain irradiation. Although results of the ongoing phase II and phase III studies are needed to confirm the benefit of hippocampal sparing brain radiotherapy on neurocognitive function, it is now technically and dosimetrically feasible to create hippocampal sparing treatment plans with appropriate irradiation of target volumes. The purpose of this review is to provide a brief overview of studies that provide a rationale for hippocampal avoidance and provide summary of published feasibility studies in order to help clinicians prepare for clinical usage of these complex and challenging techniques

  13. Protective Variant for Hippocampal Atrophy Identified by Whole Exome Sequencing

    Science.gov (United States)

    Nho, Kwangsik; Kim, Sungeun; Risacher, Shannon L.; Shen, Li; Corneveaux, Jason J.; Swaminathan, Shanker; Lin, Hai; Ramanan, Vijay K.; Liu, Yunlong; Foroud, Tatiana M.; Inlow, Mark H.; Siniard, Ashley L.; Reiman, Rebecca A.; Aisen, Paul S.; Petersen, Ronald C.; Green, Robert C.; Jack, Clifford R.; Weiner, Michael W.; Baldwin, Clinton T.; Lunetta, Kathryn L.; Farrer, Lindsay A.; Furney, Simon J.; Lovestone, Simon; Simmons, Andrew; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kloszewska, Iwona; Soininen, Hilkka; McDonald, Brenna C.; Farlow, Martin R.; Ghetti, Bernardino; Huentelman, Matthew J.; Saykin, Andrew J.

    2015-01-01

    We used whole-exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in-silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole-brain analysis and meta-analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimer’s disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next-generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets. PMID:25559091

  14. Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry

    DEFF Research Database (Denmark)

    Madsen, Kathrine Skak; Jernigan, Terry L; Iversen, Pernille

    2012-01-01

    It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is gr......It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since....... Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point...

  15. APOE ε4 is associated with disproportionate progressive hippocampal atrophy in AD.

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    Emily N Manning

    Full Text Available To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD, mild cognitive impairment (MCI and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates.MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls were used. MCI subjects were divided into "progressors" (MCI-P if diagnosed with AD within 36 months or "stable" (MCI-S if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated.Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P.These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.

  16. α-Calcium calmodulin kinase II modulates the temporal structure of hippocampal bursting patterns.

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    Jeiwon Cho

    Full Text Available The alpha calcium calmodulin kinase II (α-CaMKII is known to play a key role in CA1/CA3 synaptic plasticity, hippocampal place cell stability and spatial learning. Additionally, there is evidence from hippocampal electrophysiological slice studies that this kinase has a role in regulating ion channels that control neuronal excitability. Here, we report in vivo single unit studies, with α-CaMKII mutant mice, in which threonine 305 was replaced with an aspartate (α-CaMKII(T305D mutants, that indicate that this kinase modulates spike patterns in hippocampal pyramidal neurons. Previous studies showed that α-CaMKII(T305D mutants have abnormalities in both hippocampal LTP and hippocampal-dependent learning. We found that besides decreased place cell stability, which could be caused by their LTP impairments, the hippocampal CA1 spike patterns of α-CaMKII(T305D mutants were profoundly abnormal. Although overall firing rate, and overall burst frequency were not significantly altered in these mutants, inter-burst intervals, mean number of intra-burst spikes, ratio of intra-burst spikes to total spikes, and mean intra-burst intervals were significantly altered. In particular, the intra burst intervals of place cells in α-CaMKII(T305D mutants showed higher variability than controls. These results provide in vivo evidence that besides its well-known function in synaptic plasticity, α-CaMKII, and in particular its inhibitory phosphorylation at threonine 305, also have a role in shaping the temporal structure of hippocampal burst patterns. These results suggest that some of the molecular processes involved in acquiring information may also shape the patterns used to encode this information.

  17. Ketamine Affects the Neurogenesis of the Hippocampal Dentate Gyrus in 7-Day-Old Rats.

    Science.gov (United States)

    Huang, He; Liu, Cun-Ming; Sun, Jie; Hao, Ting; Xu, Chun-Mei; Wang, Dan; Wu, Yu-Qing

    2016-08-01

    Ketamine has been reported to cause neonatal neurotoxicity via a neuronal apoptosis mechanism; however, no in vivo research has reported whether ketamine could affect postnatal neurogenesis in the hippocampal dentate gyrus (DG). A growing number of experiments suggest that postnatal hippocampal neurogenesis is the foundation of maintaining normal hippocampus function into adulthood. Therefore, this study investigated the effect of ketamine on hippocampal neurogenesis. Male Sprague-Dawley rats were divided into two groups: the control group (equal volume of normal saline), and the ketamine-anesthesia group (40 mg/kg ketamine in four injections at 1 h intervals). The S-phase marker 5-bromodeoxyuridine (BrdU) was administered after ketamine exposure to postnatal day 7 (PND-7) rats, and the neurogenesis in the hippocampal DG was assessed using single- or double-immunofluorescence staining. The expression of GFAP in the hippocampal DG was measured by western blot analysis. Spatial reference memory was tested by Morris water maze at 2 months after PND-7 rats exposed to ketamine treatment. The present results showed that neonatal ketamine exposure significantly inhibited neural stem cell (NSC) proliferation, decreased astrocytic differentiation, and markedly enhanced neuronal differentiation. The disruptive effect of ketamine on the proliferation and differentiation of NSCs lasted at least 1 week and disappeared by 2 weeks after ketamine exposure. Moreover, the migration of newborn neurons in the granule cell layer and the growth of astrocytes in the hippocampal DG were inhibited by ketamine on PND-37 and PND-44. Finally, ketamine caused a deficit in hippocampal-dependent spatial reference memory tasks at 2 months old. Our results suggested that ketamine may interfere with hippocampal neurogenesis and long-term neurocognitive function in PND-7 rats. These findings may provide a new perspective to explain the adult neurocognitive dysfunction induced by neonatal

  18. Face-name association task reveals memory networks in patients with left and right hippocampal sclerosis

    Directory of Open Access Journals (Sweden)

    Silke Klamer

    2017-01-01

    The face-name association task can be employed to examine functional alterations of hippocampal activation during encoding of both verbal and non-verbal material in one fMRI paradigm. Further, the left SFG seems to be a convergence region for encoding of verbal and non-verbal material.

  19. Proton magnetic resonance spectroscopy of temporal lobe white matter in patients with histologically proven hippocampal sclerosis

    NARCIS (Netherlands)

    Meiners, LC; van der Grond, J; van Rijen, PC; Springorum, R; de Kort, GAP; Jansen, GH

    The purpose of this study was to assess temporal lobe white matter changes accompanying hippocampal sclerosis on magnetic resonance (MR) imaging using single-voxel H-1 MR spectroscopy and to strengthen the hypothesis that these white matter changes are caused by myelin alterations. In 11 patients

  20. Hippocampal GABA transporter distribution in patients with temporal lobe epilepsy and hippocampal sclerosis.

    Science.gov (United States)

    Schijns, Olaf; Karaca, Ümit; Andrade, Pablo; de Nijs, Laurence; Küsters, Benno; Peeters, Andrea; Dings, Jim; Pannek, Heinz; Ebner, Alois; Rijkers, Kim; Hoogland, Govert

    2015-10-01

    To determine hippocampal expression of neuronal GABA-transporter (GAT-1) and glial GABA-transporter (GAT-3) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). Hippocampal sections were immunohistochemically stained for GABA-transporter 1 and GABA-transporter-3, followed by quantification of the immunoreactivity in the hilus by optical density measurements. GABA-transporter 3 positive hilar cells were counted and GABA-transporter protein expression in sections that included all hippocampal subfields was quantified by Western blot. The hilar GABA-transporter 1 expression of patients with severe hippocampal sclerosis was about 7% lower compared to that in the mild hippocampal sclerosis/control group (psclerosis group than in the mild hippocampal sclerosis/control group (non-significant). Also, severe hippocampal sclerosis samples contained 34% less (non-significant) GABA-transporter 3 positive cells compared to that of controls. Protein expression as assessed by Western blot showed that GABA-transporter 1 was equally expressed in mild and severe hippocampal sclerosis samples, whereas GABA-transporter 3 was reduced by about 62% in severe hippocampal sclerosis samples (psclerosis. Implications for the use of GABAergic antiepileptic therapies in hippocampal sclerosis vs non-hippocampal sclerosis patients remain to be studied. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

    Science.gov (United States)

    Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

    2014-01-01

    (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.

  2. Development of a Modelling to Correlate Site and Diameter of Brain Metastases with Hippocampal Sparing Using Volumetric Modulated Arc Therapy

    Directory of Open Access Journals (Sweden)

    Silvia Chiesa

    2013-01-01

    Full Text Available Purpose. To correlate site and diameter of brain metastases with hippocampal sparing in patients treated by RapidArc (RA technique on whole brain with simultaneously integrated boost (SIB. Methods and Materials. An RA plan was calculated for brain metastases of 1-2-3 cm of diameter. The whole brain dose was 32.25 Gy (15 fractions, and SIB doses to brain metastases were 63 Gy (2 and 3 cm or 70.8 Gy (1 cm. Plans were optimized and evaluated for conformity, target coverage, prescription isodose to target volume, homogeneity index, and hippocampal sparing. Results. Fifteen brain lesions and RA plan were generated. Hippocampal volume was 4.09 cm3, and hippocampal avoidance volume was 17.50 cm3. Related to site of metastases, the mean hippocampal dose was 9.68 Gy2 for occipital lobe, 10.56 Gy2 for frontal lobe, 10.56 Gy2 for parietal lobe, 10.94 Gy2 for deep brain structures, and 40.44 Gy2 for temporal lobe. The mean hippocampal dose was 9.45 Gy2, 10.15 Gy2, and 11.70 Gy2 for diameter’s metastases of 1.2 and 3 cm, respectively, excluding results relative to temporal brain lesions. Conclusions. Location more than size of metastases can adversely influence the hippocampus sparing. Further investigation is necessary to meet definitive considerations.

  3. Aggravation of chronic stress effects on hippocampal neurogenesis and spatial memory in LPA₁ receptor knockout mice.

    Directory of Open Access Journals (Sweden)

    Estela Castilla-Ortega

    Full Text Available The lysophosphatidic acid LPA₁ receptor regulates plasticity and neurogenesis in the adult hippocampus. Here, we studied whether absence of the LPA₁ receptor modulated the detrimental effects of chronic stress on hippocampal neurogenesis and spatial memory.Male LPA₁-null (NULL and wild-type (WT mice were assigned to control or chronic stress conditions (21 days of restraint, 3 h/day. Immunohistochemistry for bromodeoxyuridine and endogenous markers was performed to examine hippocampal cell proliferation, survival, number and maturation of young neurons, hippocampal structure and apoptosis in the hippocampus. Corticosterone levels were measured in another a separate cohort of mice. Finally, the hole-board test assessed spatial reference and working memory. Under control conditions, NULL mice showed reduced cell proliferation, a defective population of young neurons, reduced hippocampal volume and moderate spatial memory deficits. However, the primary result is that chronic stress impaired hippocampal neurogenesis in NULLs more severely than in WT mice in terms of cell proliferation; apoptosis; the number and maturation of young neurons; and both the volume and neuronal density in the granular zone. Only stressed NULLs presented hypocortisolemia. Moreover, a dramatic deficit in spatial reference memory consolidation was observed in chronically stressed NULL mice, which was in contrast to the minor effect observed in stressed WT mice.These results reveal that the absence of the LPA₁ receptor aggravates the chronic stress-induced impairment to hippocampal neurogenesis and its dependent functions. Thus, modulation of the LPA₁ receptor pathway may be of interest with respect to the treatment of stress-induced hippocampal pathology.

  4. Photoperiodic regulation of hippocampal neurogenesis in adult male white-footed mice (Peromyscus leucopus).

    Science.gov (United States)

    Walton, James C; Aubrecht, Taryn G; Weil, Zachary M; Leuner, Benedetta; Nelson, Randy J

    2014-08-01

    Photoperiodic organisms monitor environmental day length to engage in seasonally appropriate adaptions in physiology and behavior. Among these adaptations are changes in brain volume and neurogenesis, which have been well described in multiple species of birds, yet few studies have described such changes in the brains of adult mammals. White-footed mice (Peromyscus leucopus) are an excellent species in which to investigate the effects of day length on adult hippocampal neurogenesis, as males, in addition to having reduced hippocampal volume in short days (SD) with concomitant impairments in hippocampus-mediated behaviors, have photoperiod-dependent changes in olfactory bulb neurogenesis. We performed the current experiment to assess the effects of photoperiod on hippocampal neurogenesis longitudinally, using the thymidine analog bromodeoxyuridine at multiple time points across 10 weeks of SD exposure. Compared with counterparts held in long day (LD) lengths, across the first 8 weeks of SD exposure hippocampal neurogenesis was reduced. However, at 10 weeks in SD lengths neurogenic levels in the hippocampus were elevated above those levels in mice held in LD lengths. The current findings are consistent with the natural photoperiodic cycle of hippocampal function in male white-footed mice, and may help to inform research on photoperiodic plasticity in neurogenesis and provide insight into how the complex interplay among the environment, genes and adaptive responses to changing day lengths affects brain structure, function and behavior at multiple levels. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. The hippocampal CA2 ensemble is sensitive to contextual change.

    Science.gov (United States)

    Wintzer, Marie E; Boehringer, Roman; Polygalov, Denis; McHugh, Thomas J

    2014-02-19

    Contextual learning involves associating cues with an environment and relating them to past experience. Previous data indicate functional specialization within the hippocampal circuit: the dentate gyrus (DG) is crucial for discriminating similar contexts, whereas CA3 is required for associative encoding and recall. Here, we used Arc/H1a catFISH imaging to address the contribution of the largely overlooked CA2 region to contextual learning by comparing ensemble codes across CA3, CA2, and CA1 in mice exposed to familiar, altered, and novel contexts. Further, to manipulate the quality of information arriving in CA2 we used two hippocampal mutant mouse lines, CA3-NR1 KOs and DG-NR1 KOs, that result in hippocampal CA3 neuronal activity that is uncoupled from the animal's sensory environment. Our data reveal largely coherent responses across the CA axis in control mice in purely novel or familiar contexts; however, in the mutant mice subject to these protocols the CA2 response becomes uncoupled from CA1 and CA3. Moreover, we show in wild-type mice that the CA2 ensemble is more sensitive than CA1 and CA3 to small changes in overall context. Our data suggest that CA2 may be tuned to remap in response to any conflict between stored and current experience.

  6. Depressive Symptoms in Adolescents: Associations with White Matter Volume and Marijuana Use

    Science.gov (United States)

    Medina, Krista Lisdahl; Nagel, Bonnie J.; Park, Ann; McQueeny, Tim; Tapert, Susan F.

    2007-01-01

    Background: Depressed mood has been associated with decreased white matter and reduced hippocampal volumes. However, the relationship between brain structure and mood may be unique among adolescents who use marijuana heavily. The goal of this study was to examine the relationship between white matter and hippocampal volumes and depressive symptoms…

  7. Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1.

    Science.gov (United States)

    Planche, Vincent; Koubiyr, Ismail; Romero, José E; Manjon, José V; Coupé, Pierrick; Deloire, Mathilde; Dousset, Vincent; Brochet, Bruno; Ruet, Aurélie; Tourdias, Thomas

    2018-04-01

    Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R 2  = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05). The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance. © 2018 Wiley Periodicals, Inc.

  8. A comparison of accurate automatic hippocampal segmentation methods.

    Science.gov (United States)

    Zandifar, Azar; Fonov, Vladimir; Coupé, Pierrick; Pruessner, Jens; Collins, D Louis

    2017-07-15

    The hippocampus is one of the first brain structures affected by Alzheimer's disease (AD). While many automatic methods for hippocampal segmentation exist, few studies have compared them on the same data. In this study, we compare four fully automated hippocampal segmentation methods in terms of their conformity with manual segmentation and their ability to be used as an AD biomarker in clinical settings. We also apply error correction to the four automatic segmentation methods, and complete a comprehensive validation to investigate differences between the methods. The effect size and classification performance is measured for AD versus normal control (NC) groups and for stable mild cognitive impairment (sMCI) versus progressive mild cognitive impairment (pMCI) groups. Our study shows that the nonlinear patch-based segmentation method with error correction is the most accurate automatic segmentation method and yields the most conformity with manual segmentation (κ=0.894). The largest effect size between AD versus NC and sMCI versus pMCI is produced by FreeSurfer with error correction. We further show that, using only hippocampal volume, age, and sex as features, the area under the receiver operating characteristic curve reaches up to 0.8813 for AD versus NC and 0.6451 for sMCI versus pMCI. However, the automatic segmentation methods are not significantly different in their performance. Copyright © 2017. Published by Elsevier Inc.

  9. MRI volumetric measurement of hippocampal formation based on statistic parametric mapping

    International Nuclear Information System (INIS)

    Hua Jianming; Jiang Biao; Zhou Jiong; Zhang Weimin

    2010-01-01

    Objective: To study MRI volumetric measurement of hippocampal formation using statistic parametric mapping (SPM) software and to discuss the value of the method applied to Alzheimer's disease (AD). Methods: The SPM software was used to divide the three-dimensional MRI brain image into gray matter, white matter and CSF separately. The bilateral hippocampal formations in both AD group and normal control group were delineated and the volumes were measured. The SPM method was compared with conventional method based on region of interest (ROI), which was the gold standard of volume measurement. The time used in measuring the volume by these two methods were respectively recorded and compared by two independent samples't test. Moreover, 7 physicians measured the left hippocampal formation of one same control with both of the two methods. The frequency distribution and dispersion of data acquired with the two methods were evaluated using standard deviation coefficient. Results (1) The volume of the bilateral hippocampal formations with SPM method was (1.88 ± 0.07) cm 3 and (1.93 ± 0.08) cm 3 respectively in the AD group, while was (2.99 ± 0.07) cm 3 and (3.02 ± 0.06) cm 3 in the control group. The volume of bilateral hippocampal formations measured by ROI method was (1.87 ± 0.06) cm 3 and (1.91 ± 0.09) cm 3 in the AD group, while was (2.97 ± 0.08) cm 3 and (3.00 ± 0.05) cm 3 in the control group. There was no significant difference between SPM method and conventional ROI method in the AD group and the control group (t=1.500, 1.617, 1.095, 1.889, P>0.05). However, the time used for delineation and volume measurement was significantly different. The time used in SPM measurement was (38.1 ± 2.0) min, while that in ROI measurement was (55.4 ± 2.4) min (t=-25.918, P 3 respectively. The frequency distribution of hippocampal formation volume measured by SPM method and ROI method was different. The CV SPM was 7% and the CV ROI was 19%. Conclusions: The borders of

  10. Preschool is a sensitive period for the influence of maternal support on the trajectory of hippocampal development

    Science.gov (United States)

    Luby, Joan L.; Belden, Andy; Harms, Michael P.; Tillman, Rebecca; Barch, Deanna M.

    2016-01-01

    Building on well-established animal data demonstrating the effects of early maternal support on hippocampal development and adaptive coping, a few longitudinal studies suggest that early caregiver support also impacts human hippocampal development. How caregiving contributes to human hippocampal developmental trajectories, whether there are sensitive periods for these effects, as well as whether related variation in hippocampal development predicts later childhood emotion functioning are of major public health importance. The current study investigated these questions in a longitudinal study of preschoolers assessed annually for behavioral and emotional development, including observed caregiver support. One hundred and twenty-seven children participated in three waves of magnetic resonance brain imaging through school age and early adolescence. Multilevel modeling of the effects of preschool and school-age maternal support on hippocampal volumes across the three waves was conducted. Hippocampal volume increased faster for those with higher levels of preschool maternal support. Subjects with support 1 SD above the mean had a 2.06 times greater increase in total hippocampus volume across the three scans than those with 1 SD below the mean (2.70% vs. 1.31%). No effect of school-age support was found. Individual slopes of hippocampus volume were significantly associated with emotion regulation at scan 3. The findings demonstrate a significant effect of early childhood maternal support on hippocampal volume growth across school age and early adolescence and suggest an early childhood sensitive period for these effects. They also show that this growth trajectory is associated with later emotion functioning. PMID:27114522

  11. More vulnerability of left than right hippocampal damage in right-handed patients with post-traumatic stress disorder.

    Science.gov (United States)

    Shu, Xi-Ji; Xue, Li; Liu, Wei; Chen, Fu-Yin; Zhu, Cheng; Sun, Xiao-Hai; Wang, Xiao-Ping; Liu, Zhong-Cun; Zhao, Hu

    2013-06-30

    Previous studies have shown hippocampal abnormalities in people with post-traumatic stress disorder (PTSD), but findings of diminished volume in shortages in the hippocampus have been inconsistent. In this study, we investigated changes in hippocampal volume and neuronal metabolites in right-handed PTSD patients to determine their possible relationship(s) with PTSD severity. We performed a case-control study of 11 right-handed PTSD patients and 11 healthy controls using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS). Hippocampal volume and metabolite ratios of N-acetylaspartate (NAA) to creatine (Cr) (NAA/Cr) and choline compounds (Cho) to Cr (Cho/Cr) were calculated. The severity of PTSD was evaluated by the Clinician-Administered PTSD Scale (CAPS). Significantly decreased left and total normalized hippocampal volumes were found in PTSD patients compared with controls (6.6% for the left hippocampus, 5.5% for total hippocampus). Also, the bilateral hippocampal NAA/Cr ratio of PTSD patients was significantly reduced compared with controls. The volume of the left hippocampus was negatively correlated to the CAPS total and CPAS-C scores. The left hippocampal NAA/Cr ratio was negatively correlated to the CAPS-total, CAPS-B, CAPS-C, and CAPS-D scores. The CAPS total and the CAPS-B scores were positively correlated to the Cho/Cr ratio of the right hippocampus. Our results indicate that hippocampal dysfunction is asymmetric in right-handed PTSD patients, with the left side affected more than the right. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Sodium-potassium ATPase emerges as a player in hippocampal phenotypes of Angelman syndrome mice.

    Science.gov (United States)

    Hallengren, Jada J; Vaden, Ryan J

    2014-07-01

    Angelman syndrome is a neurodevelopmental disorder characterized by intellectual disabilities, ataxia, and unusually happy affect. The hippocampal pyramidal cells of Angelman syndrome model mice have altered intrinsic membrane properties, which Kaphzan et al. (Cell Rep 4: 405-412, 2013) demonstrate can be corrected by genetic reduction of the α1-subunit of the sodium-potassium ATPase. Intriguingly, this manipulation also restores hippocampal long-term potentiation and learning. In this Neuro Forum, we discuss translational implications of this work and remaining questions left in its wake. Copyright © 2014 the American Physiological Society.

  13. Early Changes in Hippocampal Neurogenesis in Transgenic Mouse Models for Alzheimer's Disease.

    Science.gov (United States)

    Unger, M S; Marschallinger, J; Kaindl, J; Höfling, C; Rossner, S; Heneka, Michael T; Van der Linden, A; Aigner, Ludwig

    2016-10-01

    Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the Western world and is characterized by a progressive loss of cognitive functions leading to dementia. One major histopathological hallmark of AD is the formation of amyloid-beta plaques, which is reproduced in numerous transgenic animal models overexpressing pathogenic forms of amyloid precursor protein (APP). In human AD and in transgenic amyloid plaque mouse models, several studies report altered rates of adult neurogenesis, i.e. the formation of new neurons from neural stem and progenitor cells, and impaired neurogenesis has also been attributed to contribute to the cognitive decline in AD. So far, changes in neurogenesis have largely been considered to be a consequence of the plaque pathology. Therefore, possible alterations in neurogenesis before plaque formation or in prodromal AD have been largely ignored. Here, we analysed adult hippocampal neurogenesis in amyloidogenic mouse models of AD at different points before and during plaque progression. We found prominent alterations of hippocampal neurogenesis before plaque formation. Survival of newly generated cells and the production of new neurons were already compromised at this stage. Moreover and surprisingly, proliferation of doublecortin (DCX) expressing neuroblasts was significantly and specifically elevated during the pre-plaque stage in the APP-PS1 model, while the Nestin-expressing stem cell population was unaffected. In summary, changes in neurogenesis are evident already before plaque deposition and might contribute to well-known early hippocampal dysfunctions in prodromal AD such as hippocampal overactivity.

  14. Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory.

    Science.gov (United States)

    Kutlu, Munir Gunes; Gould, Thomas J

    2016-03-01

    The hippocampus is a key brain structure involved in synaptic plasticity associated with long-term declarative memory formation. Importantly, nicotine and activation of nicotinic acetylcholine receptors (nAChRs) can alter hippocampal plasticity and these changes may occur through modulation of hippocampal kinases and transcription factors. Hippocampal kinases such as cAMP-dependent protein kinase (PKA), calcium/calmodulin-dependent protein kinases (CAMKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and c-jun N-terminal kinase 1 (JNK1), and the transcription factor cAMP-response element-binding protein (CREB) that are activated either directly or indirectly by nicotine may modulate hippocampal plasticity and in parallel hippocampus-dependent learning and memory. Evidence suggests that nicotine may alter hippocampus-dependent learning by changing the time and magnitude of activation of kinases and transcription factors normally involved in learning and by recruiting additional cell signaling molecules. Understanding how nicotine alters learning and memory will advance basic understanding of the neural substrates of learning and aid in understanding mental disorders that involve cognitive and learning deficits. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Is radiological evaluation as good as computer-based volumetry to assess hippocampal atrophy in Alzheimer's disease?

    Energy Technology Data Exchange (ETDEWEB)

    Boutet, Claire; Drier, Aurelie; Dormont, Didier; Lehericy, Stephane [Groupe Hospitalier Pitie-Salpetriere, Department of Neuroradiology, AP-HP, Paris Cedex 13 (France); Universite Pierre et Marie Curie-Paris 6, Centre de Recherche de l' Institut du Cerveau et de la Moelle epiniere, UMR-S975, Paris (France); Inserm, Paris (France); CNRS, Paris (France); ICM-Institut du Cerveau et de la Moelle epiniere, Paris (France); Chupin, Marie; Colliot, Olivier [Universite Pierre et Marie Curie-Paris 6, Centre de Recherche de l' Institut du Cerveau et de la Moelle epiniere, UMR-S975, Paris (France); Inserm, Paris (France); CNRS, Paris (France); ICM-Institut du Cerveau et de la Moelle epiniere, Paris (France); Equipe Cogimage-CRICM, Paris Cedex 13 (France); Sarazin, Marie [Universite Pierre et Marie Curie-Paris 6, Centre de Recherche de l' Institut du Cerveau et de la Moelle epiniere, UMR-S975, Paris (France); Inserm, Paris (France); CNRS, Paris (France); ICM-Institut du Cerveau et de la Moelle epiniere, Paris (France); Groupe Hospitalier Pitie-Salpetriere, Department of Neurology, Institut de la Memoire et de la Maladie d' Alzheimer-IM2A, Paris Cedex 13 (France); Mutlu, Gurkan [Groupe Hospitalier Pitie-Salpetriere, Urgences Cerebro-Vasculaires, Universite Pierre et Marie Curie-Paris 6, Paris Cedex 13 (France); Hopital Saint-Louis, Inserm, Universite Paris 7-Denis Diderot, Paris (France); Pellot, Audrey [Groupe Hospitalier Pitie-Salpetriere, Department of Neuroradiology, AP-HP, Paris Cedex 13 (France); Collaboration: And the Alzheimer' s Disease Neuroimaging Initiative

    2012-12-15

    Hippocampus volumetry is a useful surrogate marker for the diagnosis of Alzheimer's disease (AD). Our purpose was to compare visual assessment of medial temporal lobe atrophy made by radiologists with automatic hippocampal volume and to compare their performances for the classification of AD, mild cognitive impairment (MCI) and cognitively normal (CN). We studied 30 CN, 30 MCI and 30 AD subjects. Six radiologists with two levels of expertise performed two readings of medial temporal lobe atrophy. Medial temporal lobe atrophy was evaluated on coronal three-dimensional T1-weighted images using Scheltens scale and compared with hippocampal volume obtained using a fully automatic segmentation method (Spearman's rank coefficient). Visual assessment of medial temporal lobe atrophy was correlated with hippocampal volume (p < 0.01). Classification performances between MCI converter and CN was better using volumetry than visual assessment of non-expert readers whereas classification of AD and CN did not differ between visual assessment and volumetry except for the first reading of one non-expert (p = 0.03). Visual assessment of medial temporal lobe atrophy by radiologists was well correlated with hippocampal volume. Radiological assessment is as good as computer-based volumetry for the classification of AD, MCI non-converter and CN and less good for the classification of MCI converter versus CN. Use of Scheltens scale for assessing hippocampal atrophy in AD seems thus justified in clinical routine. (orig.)

  16. Long-term potentiation expands information content of hippocampal dentate gyrus synapses.

    Science.gov (United States)

    Bromer, Cailey; Bartol, Thomas M; Bowden, Jared B; Hubbard, Dusten D; Hanka, Dakota C; Gonzalez, Paola V; Kuwajima, Masaaki; Mendenhall, John M; Parker, Patrick H; Abraham, Wickliffe C; Sejnowski, Terrence J; Harris, Kristen M

    2018-03-06

    An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.

  17. Methamphetamine-induced changes in the mice hippocampal neuropeptide Y system: implications for memory impairment

    DEFF Research Database (Denmark)

    Gonçalves, J; Baptista, S; Olesen, MV

    2012-01-01

    , being involved in learning and memory processing. It has been demonstrated that METH induces significant alteration in mice striatal NPY, Y(1) and Y(2) receptor mRNA levels. However, the impact of this drug on the hippocampal NPY system and its consequences remain unknown. Thus, in this study, we...... investigated the effect of METH intoxication on mouse hippocampal NPY levels, NPY receptors function, and memory performance. Results show that METH increased NPY, Y(2) and Y(5) receptor mRNA levels, as well as total NPY binding accounted by opposite up- and down-regulation of Y(2) and Y(1) functional binding......, respectively. Moreover, METH-induced impairment in memory performance and AKT/mammalian target of rapamycin pathway were both prevented by the Y(2) receptor antagonist, BIIE0246. These findings demonstrate that METH interferes with the hippocampal NPY system, which seems to be associated with memory failure...

  18. Is the type and extent of hippocampal sclerosis measurable on high-resolution MRI?

    Energy Technology Data Exchange (ETDEWEB)

    Urbach, H; Schwarzwald, R [Medical Center University of Freiburg, Dept. of Neuroradiology, Freiburg (Germany); Huppertz, H.J. [Swiss Epilepsy Center, Zurich (Switzerland); Becker, A.J. [Medical Center University of Bonn, Department of Neuropathology, Bonn (Germany); Wagner, J. [Medical Center University of Bonn, Department of Epileptology, Bonn (Germany); Bahri, M. Delsous; Tschampa, H.J. [Medical Center University of Bonn, Department of Radiology/Neuroradiology, Bonn (Germany)

    2014-09-15

    The purpose of this study is to relate hippocampal volume and FLAIR signal intensity to Wyler grading of hippocampal sclerosis (HS). Of 100 consecutive patients with temporal lobe epilepsy and HS as histopathological diagnosis, 32 had high-resolution 3 Tesla MRI and anatomically well-preserved hippocampi following amygdalo-hippocampectomy. Hippocampal volume on 3D T1-weighted gradient echo and signal intensity on coronal FLAIR sequences were determined using FreeSurfer and SPM tools and related to Wyler grading. Seizure outcome was determined after 1 year. Histopathology showed four Wyler II, 19 Wyler III, and 9 Wyler IV HS. Hippocampal volumes were 3.08 ml for Wyler II (Wyler II/contralateral side: p > 0.05), 2.19 ml for Wyler III (p < 0.01), 2.62 ml for Wyler IV (p = 0.01), and 3.08 ml for the contralateral side. Normalized FLAIR signals were 1,354 (p = 0.0004), 1,408 (p < 0.0001), 1,371 (p < 0.04), and 1,296, respectively. Wyler II hippocampi were visually normal. Two of four (50 %) Wyler II, 16/19 (84 %) Wyler III, and 6/9 (66 %) Wyler IV patients achieved Engel I outcome. Combined volumetry and quantitative FLAIR signal analysis clearly identifies Wyler III and IV HS. Quantitative FLAIR signal analysis may be helpful to identify Wyler II HS. (orig.)

  19. Overexpression of Dyrk1A is implicated in several cognitive, electrophysiological and neuromorphological alterations found in a mouse model of Down syndrome.

    Directory of Open Access Journals (Sweden)

    Susana García-Cerro

    Full Text Available Down syndrome (DS phenotypes result from the overexpression of several dosage-sensitive genes. The DYRK1A (dual-specificity tyrosine-(Y-phosphorylation regulated kinase 1A gene, which has been implicated in the behavioral and neuronal alterations that are characteristic of DS, plays a role in neuronal progenitor proliferation, neuronal differentiation and long-term potentiation (LTP mechanisms that contribute to the cognitive deficits found in DS. The purpose of this study was to evaluate the effect of Dyrk1A overexpression on the behavioral and cognitive alterations in the Ts65Dn (TS mouse model, which is the most commonly utilized mouse model of DS, as well as on several neuromorphological and electrophysiological properties proposed to underlie these deficits. In this study, we analyzed the phenotypic differences in the progeny obtained from crosses of TS females and heterozygous Dyrk1A (+/- male mice. Our results revealed that normalization of the Dyrk1A copy number in TS mice improved working and reference memory based on the Morris water maze and contextual conditioning based on the fear conditioning test and rescued hippocampal LTP. Concomitant with these functional improvements, normalization of the Dyrk1A expression level in TS mice restored the proliferation and differentiation of hippocampal cells in the adult dentate gyrus (DG and the density of GABAergic and glutamatergic synapse markers in the molecular layer of the hippocampus. However, normalization of the Dyrk1A gene dosage did not affect other structural (e.g., the density of mature hippocampal granule cells, the DG volume and the subgranular zone area or behavioral (i.e., hyperactivity/attention alterations found in the TS mouse. These results suggest that Dyrk1A overexpression is involved in some of the cognitive, electrophysiological and neuromorphological alterations, but not in the structural alterations found in DS, and suggest that pharmacological strategies targeting

  20. Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique.

    Science.gov (United States)

    Brodin, N Patrik; Munck af Rosenschöld, Per; Blomstrand, Malin; Kiil-Berthlesen, Anne; Hollensen, Christian; Vogelius, Ivan R; Lannering, Birgitta; Bentzen, Søren M; Björk-Eriksson, Thomas

    2014-04-01

    We investigated how varying the treatment margin and applying hippocampal sparing and proton therapy impact the risk of neurocognitive impairment in pediatric medulloblastoma patients compared with current standard 3D conformal radiotherapy. We included 17 pediatric medulloblastoma patients to represent the variability in tumor location relative to the hippocampal region. Treatment plans were generated using 3D conformal radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot-scanned proton therapy, using 3 different treatment margins for the conformal tumor boost. Neurocognitive impairment risk was estimated based on dose-response models from pediatric CNS malignancy survivors and compared among different margins and treatment techniques. Mean hippocampal dose and corresponding risk of cognitive impairment were decreased with decreasing treatment margins (P < .05). The largest risk reduction, however, was seen when applying hippocampal sparing proton therapy-the estimated risk of impaired task efficiency (95% confidence interval) was 92% (66%-98%), 81% (51%-95%), and 50% (30%-70%) for 3D conformal radiotherapy, intensity-modulated radiotherapy, and proton therapy, respectively, for the smallest boost margin and 98% (78%-100%), 90% (60%-98%), and 70% (39%-90%) if boosting the whole posterior fossa. Also, the distance between the closest point of the planning target volume and the center of the hippocampus can be used to predict mean hippocampal dose for a given treatment technique. We estimate a considerable clinical benefit of hippocampal sparing radiotherapy. In choosing treatment margins, the tradeoff between margin size and risk of neurocognitive impairment quantified here should be considered.

  1. Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer's disease.

    Science.gov (United States)

    Dubois, Bruno; Chupin, Marie; Hampel, Harald; Lista, Simone; Cavedo, Enrica; Croisile, Bernard; Louis Tisserand, Guy; Touchon, Jacques; Bonafe, Alain; Ousset, Pierre Jean; Ait Ameur, Amir; Rouaud, Olivier; Ricolfi, Fréderic; Vighetto, Alain; Pasquier, Florence; Delmaire, Christine; Ceccaldi, Mathieu; Girard, Nadine; Dufouil, Carole; Lehericy, Stéphane; Tonelli, Isabelle; Duveau, Françoise; Colliot, Olivier; Garnero, Line; Sarazin, Marie; Dormont, Didier

    2015-09-01

    The purpose of this study was to study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD). A double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent two brain magnetic resonance imaging scans (baseline and final visit). The primary efficacy outcome was the annualized percentage change (APC) of total hippocampal volume (left + right) measured by an automated segmentation method. Two-hundred and sixteen only subjects were randomized across 28 French expert clinical sites. In the per protocol population (placebo = 92 and donepezil = 82), the donepezil group exhibited a significant reduced rate of hippocampal atrophy (APC = -1.89%) compared with the placebo group (APC = -3.47%), P donepezil compared with placebo. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  2. Maternal vitamin C deficiency during pregnancy persistently impairs hippocampal neurogenesis in offspring of guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Vogt, Lucile; Schjoldager, Janne G

    2012-01-01

    While having the highest vitamin C (VitC) concentrations in the body, specific functions of VitC in the brain have only recently been acknowledged. We have shown that postnatal VitC deficiency in guinea pigs causes impairment of hippocampal memory function and leads to 30% less neurons. This study...... investigates how prenatal VitC deficiency affects postnatal hippocampal development and if any such effect can be reversed by postnatal VitC repletion. Eighty pregnant Dunkin Hartley guinea pig dams were randomized into weight stratified groups receiving High (900 mg) or Low (100 mg) VitC per kg diet. Newborn...... by stereology. Prenatal VitC deficiency resulted in a significant reduction in postnatal hippocampal volume (P...

  3. Protective effects of hydroponic Teucrium polium on hippocampal neurodegeneration in ovariectomized rats.

    Science.gov (United States)

    Simonyan, K V; Chavushyan, V A

    2016-10-24

    The hippocampus is a target of ovarian hormones, and is necessary for memory. Ovarian hormone loss is associated with a progressive reduction in synaptic strength and dendritic spine. Teucrium polium has beneficial effects on learning and memory. However, it remains unknown whether Teucrium polium ameliorates hippocampal cells spike activity and morphological impairments induced by estrogen deficiency. In the present study, we investigated the effects of hydroponic Teucrium polium on hippocampal neuronal activity and morpho-histochemistry of bilateral ovariectomized (OVX) rats. Tetanic potentiation or depression with posttetanic potentiation and depression was recorded extracellularly in response to ipsilateral entorhinal cortex high frequency stimulation. In morpho-histochemical study revealing of the activity of Ca 2+ -dependent acid phosphatase was observed. In all groups (sham-operated, sham + Teucrium polium, OVX, OVX + Teucrium polium), most recorded hippocampal neurons at HFS of entorhinal cortex showed TD-PTP responses. After 8 weeks in OVX group an anomalous evoked spike activity was detected (a high percentage of typical areactive units). In OVX + Teucrium polium group a synaptic activity was revealed, indicating prevention OVX-induced degenerative alterations: balance of types of responses was close to norm and areactive units were not recorded. All recorded neurons in sham + Teucrium polium group were characterized by the highest mean frequency background and poststimulus activity. In OVX+ Teucrium polium group the hippocampal cells had recovered their size and shape in CA1 and CA3 field compared with OVX group where hippocampal cells were characterized by a sharp drop in phosphatase activity and there was a complete lack of processes reaction. Thus, Teucrium polium reduced OVX-induce neurodegenerative alterations in entorhinal cortex-hippocamp circuitry and facilitated neuronal survival by modulating activity of neurotransmitters and

  4. Susceptibility to hippocampal kindling seizures is increased in aging C57 black mice

    Directory of Open Access Journals (Sweden)

    Kurt R. Stover

    2017-12-01

    Full Text Available The incidence of seizures increases with old age. Stroke, dementia and brain tumors are recognized risk factors for new-onset seizures in the aging populations and the incidence of these conditions also increased with age. Whether aging is associated with higher seizure susceptibility in the absence of the above pathologies remains unclear. We used classic kindling to explore this issue as the kindling model is highly reproducible and allows close monitoring of electrographic and motor seizure activities in individual animals. We kindled male young and aging mice (C57BL/6 strain, 2–3 and 18–22 months of age via daily hippocampal CA3 stimulation and monitored seizure activity via video and electroencephalographic recordings. The aging mice needed fewer stimuli to evoke stage-5 motor seizures and exhibited longer hippocampal afterdischarges and more frequent hippocampal spikes relative to the young mice, but afterdischarge thresholds and cumulative afterdischarge durations to stage 5 motor seizures were not different between the two age groups. While hippocampal injury and structural alterations at cellular and micro-circuitry levels remain to be examined in the kindled mice, our present observations suggest that susceptibility to hippocampal CA3 kindling seizures is increased with aging in male C57 black mice.

  5. Changes in reward contingency modulate the trial-to-trial variability of hippocampal place cells.

    Science.gov (United States)

    Wikenheiser, Andrew M; Redish, A David

    2011-08-01

    Pyramidal cells in the rodent hippocampus often exhibit clear spatial tuning. Theories of hippocampal function suggest that these "place cells" implement multiple, independent neural representations of position (maps), based on different reference frames or environmental features. Consistent with the "multiple maps" theory, previous studies have shown that manipulating spatial factors related to task performance modulates the within-session variability (overdispersion) of cells in the hippocampus. However, the influence of changes in reward contingency on overdispersion has not been examined. To test this, we first trained rats to collect food from three feeders positioned around a circular track (task(1)). When subjects were proficient, the reward contingency was altered such that every other feeder delivered food (task(2)). We recorded ensembles of hippocampal neurons as rats performed both tasks. Place cell overdispersion was high during task(1) but decreased significantly during task(2), and this increased reliability could not be accounted for by changes in running speed or familiarity with the task. Intuitively, decreased variability might be expected to improve neural representations of position. To test this, we used Bayesian decoding of hippocampal spike trains to estimate subjects' location. Neither the amount of probability decoded to subjects' position (local probability) nor the difference between estimated position and true location (decoding accuracy) differed between tasks. However, we found that hippocampal ensembles were significantly more self-consistent during task(2) performance. These results suggest that changes in task demands can affect the firing statistics of hippocampal neurons, leading to changes in the properties of decoded neural representations.

  6. DEVELOPMENTAL HYPOTHYROIDISM ALTERS SYNAPTIC TRANSMISSION IN DENTATE GYRUS AND AREA CA1 OF HIPPOCAMPUS.

    Science.gov (United States)

    Hypothyroidism during critical periods of brain developmental leads to learning deficits and alterations in hippocampal structure. Neurophysiological properties of the hippocampus, however, have not been well characterized. The present study examined field potentials evoked in...

  7. Hippocampal Dendritic Spines Modifications Induced by Perinatal Asphyxia

    Directory of Open Access Journals (Sweden)

    G. E. Saraceno

    2012-01-01

    Full Text Available Perinatal asphyxia (PA affects the synaptic function and morphological organization. In previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia leading to long-term ubi-protein accumulation. Since F-actin is highly concentrated in dendritic spines, modifications in its organization could be related with alterations induced by hypoxia in the central nervous system (CNS. In the present study, we investigate the effects of PA on the actin cytoskeleton of hippocampal postsynaptic densities (PSD in 4-month-old rats. PSD showed an increment in their thickness and in the level of ubiquitination. Correlative fluorescence-electron microscopy photooxidation showed a decrease in the number of F-actin-stained spines in hippocampal excitatory synapses subjected to PA. Although Western Blot analysis also showed a slight decrease in β-actin in PSD in PA animals, the difference was not significant. Taken together, this data suggests that long-term actin cytoskeleton might have role in PSD alterations which would be a spread phenomenon induced by PA.

  8. Amyloid Beta Peptides Differentially Affect Hippocampal Theta Rhythms In Vitro

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    Armando I. Gutiérrez-Lerma

    2013-01-01

    Full Text Available Soluble amyloid beta peptide (Aβ is responsible for the early cognitive dysfunction observed in Alzheimer's disease. Both cholinergically and glutamatergically induced hippocampal theta rhythms are related to learning and memory, spatial navigation, and spatial memory. However, these two types of theta rhythms are not identical; they are associated with different behaviors and can be differentially modulated by diverse experimental conditions. Therefore, in this study, we aimed to investigate whether or not application of soluble Aβ alters the two types of theta frequency oscillatory network activity generated in rat hippocampal slices by application of the cholinergic and glutamatergic agonists carbachol or DHPG, respectively. Due to previous evidence that oscillatory activity can be differentially affected by different Aβ peptides, we also compared Aβ25−35 and Aβ1−42 for their effects on theta rhythms in vitro at similar concentrations (0.5 to 1.0 μM. We found that Aβ25−35 reduces, with less potency than Aβ1−42, carbachol-induced population theta oscillatory activity. In contrast, DHPG-induced oscillatory activity was not affected by a high concentration of Aβ25−35 but was reduced by Aβ1−42. Our results support the idea that different amyloid peptides might alter specific cellular mechanisms related to the generation of specific neuronal network activities, instead of exerting a generalized inhibitory effect on neuronal network function.

  9. Regional Hippocampal Atrophy and Higher Levels of Plasma Amyloid-Beta Are Associated With Subjective Memory Complaints in Nondemented Elderly Subjects

    DEFF Research Database (Denmark)

    Cantero, Jose L; Iglesias, Juan E.; Van Leemput, Koen

    2016-01-01

    volume differences in hippocampal subregions were further correlated with plasma Aβ levels and with objective memory performance. Results: Individuals with SMC exhibited significantly higher Aβ1-42 concentrations and lower volumes of CA1, CA4, dentate gyrus, and molecular layer compared with SMC......(-) participants. Regression analyses further showed significant associations between lower volume of the dentate gyrus and both poorer memory performance and higher plasma Aβ1-42 levels in SMC(+) participants. Conclusions: The presence of SMC, lower volumes of specific hippocampal regions, and higher plasma Aβ1...

  10. Hippocampal phosphoproteomics of F344 rats exposed to 1-bromopropane

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenlie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ichihara, Sahoko [Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Chang, Jie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507 (Japan); Zhang, Lingyi [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan); Hu, Shijie [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Huang, Hanlin, E-mail: huanghl@gdoh.org [Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510-300 (China); Ichihara, Gaku, E-mail: gak@rs.tus.ac.jp [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Department of Occupational and Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510 (Japan)

    2015-01-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and human. To identify phosphorylated modification on the unrecognized post-translational modifications of proteins and investigate their role in 1-BP-induced neurotoxicity, changes in hippocampal phosphoprotein expression levels were analyzed quantitatively in male F344 rats exposed to 1-BP inhalation at 0, 400, or 1000 ppm for 8 h/day for 1 or 4 weeks. Hippocampal protein extracts were analyzed qualitatively and quantitatively by Pro-Q Diamond gel staining and SYPRO Ruby staining coupled with two-dimensional difference in gel electrophoresis (2D-DIGE), respectively, as well as by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to identify phosphoproteins. Changes in selected proteins were further confirmed by Manganese II (Mn{sup 2+})-Phos-tag SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Bax and cytochrome c protein levels were determined by western blotting. Pro-Q Diamond gel staining combined with 2D-DIGE identified 26 phosphoprotein spots (p < 0.05), and MALDI-TOF/MS identified 18 up-regulated proteins and 8 down-regulated proteins. These proteins are involved in the biological process of response to stimuli, metabolic processes, and apoptosis signaling. Changes in the expression of phosphorylated 14-3-3 θ were further confirmed by Mn{sup 2+}-Phos-tag SDS-PAGE. Western blotting showed overexpression of Bax protein in the mitochondria with down-regulation in the cytoplasm, whereas cytochrome c expression was high in the cytoplasm but low in the mitochondria after 1-BP exposure. Our results suggest that the pathogenesis of 1-BP-induced hippocampal damage involves inhibition of antiapoptosis process. Phosphoproteins identified in this study can potentially serve as biomarkers for 1-BP-induced neurotoxicity. - Highlights: • 1-BP modified hippocampal phosphoproteome in rat and 23 altered proteins were identified. • 1-BP changed phosphorylation

  11. TNF-α from hippocampal microglia induces working memory deficits by acute stress in mice.

    Science.gov (United States)

    Ohgidani, Masahiro; Kato, Takahiro A; Sagata, Noriaki; Hayakawa, Kohei; Shimokawa, Norihiro; Sato-Kasai, Mina; Kanba, Shigenobu

    2016-07-01

    The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-α levels were significantly elevated after acute stress, and acute stress-induced TNF-α was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-α were not elevated after acute stress. Etanercept (TNF-α inhibitor) recovered working memory deficits in accordance with hippocampal TNF-α reductions. Overall, results suggest that TNF-α from hippocampal microglia is a key contributor to early-stage stress-to-mental responses. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Hippocampal pathway plasticity is associated with the ability to form novel memories in older adults

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    Daria eAntonenko

    2016-03-01

    Full Text Available White matter deterioration in the aging human brain contributes to cognitive decline. The fornix as main efferent hippocampal pathway is one of the tracts most strongly associated with age-related memory impairment. Its deterioration may predict conversion to Alzheimer’s dementia and its precursors. However, the associations between the ability to form novel memories, fornix microstructure and plasticity in response to training have never been tested. In the present study, 25 healthy older adults (15 women; mean age (SD: 69 (6 years underwent an object-location training on three consecutive days. Behavioral outcome measures comprised recall performance on the training days, and on 1-day and 1-month follow up assessments. MRI at 3 Tesla was assessed before and after training. Fornix microstructure was determined by fractional anisotropy and mean diffusivity values from diffusion tensor imaging (DTI. In addition, hippocampal volumes were extracted from high-resolution images; individual hippocampal masks were further aligned to DTI images to determine hippocampal microstructure. Using linear mixed model analysis, we found that the change in fornix FA from pre- to post-training assessment was significantly associated with training success. Neither baseline fornix microstructure nor hippocampal microstructure or volume changes were significantly associated with performance. Further, models including control task performance (auditory verbal learning and control white matter tract microstructure (uncinate fasciculus and parahippocampal cingulum did not yield significant associations. Our results confirm that hippocampal pathways respond to short-term cognitive training, and extend previous findings by demonstrating that the magnitude of training-induced structural changes is associated with behavioral success in older adults. This suggests that the amount of fornix plasticity may not only be behaviorally relevant, but also a potential sensitive

  13. Visual performance of pigeons following hippocampal lesions.

    Science.gov (United States)

    Bingman, V P; Hodos, W

    1992-11-15

    The effect of hippocampal lesions on performance in two psychophysical measures of spatial vision (acuity and size-difference threshold) was examined in 7 pigeons. No difference between the preoperative and postoperative thresholds of the experimental birds was found. The visual performance of pigeons in the psychophysical tasks failed to reveal a role of the hippocampal formation in vision. The results argue strongly that the behavioral deficits found in pigeons with hippocampal lesions when tested in a variety of memory-related spatial tasks is not based on a defect in spatial vision but impaired spatial cognition.

  14. Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230.

    Science.gov (United States)

    Egger, Christine; Gérard, Christelle; Vidotto, Nella; Accart, Nathalie; Cannet, Catherine; Dunbar, Andrew; Tigani, Bruno; Piaia, Alessandro; Jarai, Gabor; Jarman, Elizabeth; Schmid, Herbert A; Beckmann, Nicolau

    2014-06-15

    Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRI-assessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis. Copyright © 2014 the American Physiological Society.

  15. Both oophorectomy and obesity impaired solely hippocampal-dependent memory via increased hippocampal dysfunction.

    Science.gov (United States)

    Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-04-17

    Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.

  16. Postnatal stimulation of the pups counteracts prenatal stress-induced deficits in hippocampal neurogenesis.

    Science.gov (United States)

    Lemaire, Valerie; Lamarque, Stephanie; Le Moal, Michel; Piazza, Pier-Vincenzo; Abrous, Djoher Nora

    2006-05-01

    Prenatal stress constitutes a developmental risk factor for later psychopathology. The behavioral disorders are sustained by neurobiological alterations including long-term reduction of hippocampal neurogenesis; its deregulation has been involved in cognitive impairments, mood disorders and addiction. A major goal is to define periods in development and strategies for intervening to prevent the effects of early stressful events. We investigated the ability of a postnatal infantile stimulation to prevent prenatal stress-induced alteration in hippocampal neurogenesis. The influence of postnatal handling on prenatal stress-induced changes in hippocampal neurogenesis was examined in 4 and 26 month-old male rats. Three distinct phases of the neurogenesis were studied: proliferation, survival and neuronal differentiation. Prenatal stress reduced hippocampal cell proliferation all throughout life. Furthermore, the survival rate of newborn cells, the number of immature neurons and the number of differentiated new neurons were reduced in young and old prenatally-stressed rats. All those deleterious effects were counteracted by neonatal handling. These data show that finer aspects of brain shaping can be rewired by environmental influences occurring at sensitive phase of development. They also suggest that infantile stimulation may reverse the appearance of behavioral disorders induced by early life stress.

  17. Analysis of parahippocampal gyrus in 115 patients with hippocampal sclerosis

    Directory of Open Access Journals (Sweden)

    Ferreira Nelson Fortes

    2003-01-01

    Full Text Available PURPOSE: Analysis of the parahippocampal gyrus (PHG involvement in 115 patients with hippocampal sclerosis (HS by MR imaging. The simultaneous occurrence of ipsilateral fornix (F and mamillary body (MB volume loss was checked also. These findings were correlated with the side of hippocampal involvement, the sex, patient´s age, and the symptoms onset. METHOD: The MR images of 115 patients with HS were studied retrospectively. All the examinations were performed on 1.5 T units (SIGNA, GE, Milwaukee, WI and included high resolution coronal T2-weighted images (3 mm thickness, 0.6 mm gap. RESULTS: The patient's age ranged between 3.5 and 80 years (mean 34.1; 62 (53.9% were female and 53 (46.1% were male. There were HS on the left side in 53 (46.0%, on the right side in 51 (44.3%, and bilateral in 11 (9.7%. In 43 (37.3% cases there were ipsilateral PHG volume loss and signal hyper intensity on T2-weighted imaging. In 29 (25.2% cases there were ipsilateral fornix volume loss and in 10 (34.5% of this there were also ipsilateral MB changes. In abnormal PHG, 23 (53.4% were on the left side, 17 (39.5% were on the right side, and 3 (7.1% were bilateral. There were fornix changes in 15 (34.8% cases and MB volume loss in 5 (11.6% cases. Pertinent clinical data were obtained in only 18 (41.8% of the PHG lesion cases and 11 (61.1% of these patients had epileptic attacks for more than 20 years before the examination. CONCLUSION: PHG involvement must be investigated in patients with HS and we suggest that the term mesial temporal sclerosis should be used only if there are also changes at this anatomical site.

  18. Elevated CYP2C19 expression is associated with depressive symptoms and hippocampal homeostasis impairment.

    Science.gov (United States)

    Jukić, M M; Opel, N; Ström, J; Carrillo-Roa, T; Miksys, S; Novalen, M; Renblom, A; Sim, S C; Peñas-Lledó, E M; Courtet, P; Llerena, A; Baune, B T; de Quervain, D J; Papassotiropoulos, A; Tyndale, R F; Binder, E B; Dannlowski, U; Ingelman-Sundberg, M

    2017-08-01

    The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype. In humans, we found that the absence of CYP2C19 was associated with a bilateral hippocampal volume increase in two independent healthy cohorts (N=386 and 1032) and a lower prevalence of major depressive disorder and depression severity in African-Americans (N=3848). Moreover, genetically determined high CYP2C19 enzymatic capacity was associated with higher suicidality in depressed suicide attempters (N=209). 2C19TG mice showed high stress sensitivity, impaired hippocampal Bdnf homeostasis in stress, and more despair-like behavior in the forced swim test (FST). After the treatment with citalopram and 5-HT 1A receptor agonist 8OH-DPAT, the reduction in immobility time in the FST was more pronounced in 2C19TG mice compared with WTs. Conversely, in the 2C19TG hippocampus, metabolic turnover of serotonin was reduced, whereas ERK1/2 and GSK3β phosphorylation was increased. Altogether, this study indicates that elevated CYP2C19 expression is associated with depressive symptoms, reduced hippocampal volume and impairment of hippocampal serotonin and BDNF homeostasis.

  19. Hippocampal synaptic plasticity, spatial memory and anxiety

    OpenAIRE

    Bannerman, David M.; Sprengel, Rolf; Sanderson, David J.; McHugh, Stephen B.; Rawlins, J. Nicholas P.; Monyer, Hannah; Seeburg, Peter H.

    2014-01-01

    Recent studies using transgenic mice lacking NMDA receptors in the hippocampus challenge the long-standing hypothesis that hippocampal long-term potentiation-like mechanisms underlie the encoding and storage of associative long-term spatial memories. However, it may not be the synaptic plasticity-dependent memory hypothesis that is wrong; instead, it may be the role of the hippocampus that needs to be re-examined. We present an account of hippocampal function that explains its role in both me...

  20. Cavernous angioma associated with ipsilateral hippocampal sclerosis

    International Nuclear Information System (INIS)

    Okujava, M.; Ebner, A.; Schmitt, J.; Woermann, F.G.

    2002-01-01

    We report two cases with extratemporal cavernous angioma (CA) and coexisting ipsilateral hippocampal sclerosis. Classically dual pathology is defined as the association of hippocampal sclerosis with an extrahippocampal lesion. Subtle changes in hippocampus might be overlooked in the presence of an unequivocal extrahippocampal abnormality. Seizure outcome after epilepsy surgery in cases with dual pathology is less favourable if only one of the lesions is removed. Dual pathology must always be considered in diagnostic imaging of patients with intractable epilepsy and CA. (orig.)

  1. Hippocampal correlates of aversive mibdrain stimulation.

    Science.gov (United States)

    Routtenberg, A; Kramis, R C

    1968-06-21

    Hippocampal synchronization during aversive dorsal midbrain stimulation was observed in rats both in a conditioning procedure and under d-tubo-curarine paralysis. The results restrict the generality of previous reports which correlated hippocampal synchronization and desynchronization with approach and withdrawal behavior, respectively. Relative to the condition of free movement, curarization reduced the frequency of both "spontaneous" and dorsal midbrain-evoked synchronization, thus suggesting possible direct and indirect effects of d-tubocurarine on subcortical structures.

  2. Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.

    Science.gov (United States)

    Le Barillier, Léa; Léger, Lucienne; Luppi, Pierre-Hervé; Fort, Patrice; Malleret, Gaël; Salin, Paul-Antoine

    2015-11-01

    The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.

  3. Hippocampal Astrocytes in Migrating and Wintering Semipalmated Sandpiper Calidris pusilla

    Directory of Open Access Journals (Sweden)

    Dario Carvalho-Paulo

    2018-01-01

    Full Text Available Seasonal migratory birds return to the same breeding and wintering grounds year after year, and migratory long-distance shorebirds are good examples of this. These tasks require learning and long-term spatial memory abilities that are integrated into a navigational system for repeatedly locating breeding, wintering, and stopover sites. Previous investigations focused on the neurobiological basis of hippocampal plasticity and numerical estimates of hippocampal neurogenesis in birds but only a few studies investigated potential contributions of glial cells to hippocampal-dependent tasks related to migration. Here we hypothesized that the astrocytes of migrating and wintering birds may exhibit significant morphological and numerical differences connected to the long-distance flight. We used as a model the semipalmated sandpiper Calidris pusilla, that migrates from northern Canada and Alaska to South America. Before the transatlantic non-stop long-distance component of their flight, the birds make a stopover at the Bay of Fundy in Canada. To test our hypothesis, we estimated total numbers and compared the three-dimensional (3-D morphological features of adult C. pusilla astrocytes captured in the Bay of Fundy (n = 249 cells with those from birds captured in the coastal region of Bragança, Brazil, during the wintering period (n = 250 cells. Optical fractionator was used to estimate the number of astrocytes and for 3-D reconstructions we used hierarchical cluster analysis. Both morphological phenotypes showed reduced morphological complexity after the long-distance non-stop flight, but the reduction in complexity was much greater in Type I than in Type II astrocytes. Coherently, we also found a significant reduction in the total number of astrocytes after the transatlantic flight. Taken together these findings suggest that the long-distance non-stop flight altered significantly the astrocytes population and that morphologically distinct astrocytes

  4. Effect of Integrated Cognitive Therapy on Hippocampal Functional Connectivity Patterns in Stroke Patients with Cognitive Dysfunction: A Resting-State fMRI Study

    Directory of Open Access Journals (Sweden)

    Shanli Yang

    2014-01-01

    Full Text Available Objective. This study aimed to identify abnormal hippocampal functional connectivity (FC following ischemic stroke using resting-state fMRI. We also explored whether abnormal hippocampal FC could be modulated by integrated cognitive therapy and tested whether these alterations were associated with cognitive performance. Methods. 18 right-handed cognitively impaired ischemic stroke patients and 18 healty control (HC subjects were included in this study. Stroke subjects were scanned at baseline and after integrated cognitive therapy, while HCs were only scanned at baseline, to identify regions that show significant correlations with the seed region. Behavioral and cognitive assessments were obtained before each scan. Results. During the resting state, we found abnormal hippocampal FC associated with temporal regions, insular cortex, cerebellum, and prefrontal cortex in stroke patients compared to HCs. After integrated cognitive therapy, however, the stroke group showed increased hippocampal FC mainly located in the prefrontal gyrus and the default mode network (DMN. Altered hippocampal FC was associated with cognitive improvement. Conclusion. Resting-state fMRI may provide novel insight into the study of functional networks in the brain after stroke. Furthermore, altered hippocampal FC may be a compensatory mechanism for cognitive recovery after ischemic stroke.

  5. Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence.

    Science.gov (United States)

    Cooper, Janine M; Gadian, David G; Jentschke, Sebastian; Goldman, Allan; Munoz, Monica; Pitts, Georgia; Banks, Tina; Chong, W Kling; Hoskote, Aparna; Deanfield, John; Baldeweg, Torsten; de Haan, Michelle; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-06-01

    Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life. © The Author 2013. Published by Oxford University Press.

  6. Quercetin alters uterine fluid volume and aquaporin (AQP) subunits (AQP-1, 2, 5 & 7) expression in the uterus in the presence of sex-steroids in rats.

    Science.gov (United States)

    Shahzad, Huma; Giribabu, Nelli; Karim, Kamarulzaman; Muniandy, Sekaran; Kassim, Normadiah M; Salleh, Naguib

    2017-04-01

    Effects of quercetin on uterine fluid volume and aquaporin (AQP) expression in the uterus were investigated. Estradiol (E) or estradiol followed by progesterone (E+P) were given to ovariectomised rats with or without quercetin (10, 50 or 100mg/kg/day) treatment. Uteri were harvested and its inner/outer circumference ratio was determined. AQP-1, 2, 5 and 7 mRNA and protein levels in uterus were quantified by Real-time PCR and Western blotting respectively. Protein distribution was observed by immunohistochemistry. Administration of quercetin in E-treated rats decreased the uterine fluid volume and uterine AQP-2 expression. In E+P-treated rats, administration of 100mg/kg/day quercetin increased uterine fluid volume, AQP-1 and 2 expression but decreased AQP-7 expression in uterus. AQP-1 was distributed in stromal blood vessels while AQP-2, 5 and 7 were distributed in uterine epithelium. Quercetin-induced changes in uterine fluid volume and AQP subunits expression in uterus could affect the uterine reproductive functions under different sex-steroid influence. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Dietary lipids are differentially associated with hippocampal-dependent relational memory in prepubescent children1234

    Science.gov (United States)

    Khan, Naiman A; Monti, Jim M; Raine, Lauren B; Drollette, Eric S; Moore, R Davis; Scudder, Mark R; Kramer, Arthur F; Hillman, Charles H; Cohen, Neal J

    2014-01-01

    Background: Studies in rodents and older humans have shown that the hippocampus—a brain structure critical to relational/associative memory—has remarkable plasticity as a result of lifestyle factors (eg, exercise). However, the effect of dietary intake on hippocampal-dependent memory during childhood has remained unexamined. Objective: We investigated the cross-sectional relation of dietary components characteristic of the Western diet, including saturated fatty acids (SFAs), omega-3 (n−3) fatty acids, and refined sugar, with hippocampal-dependent relational memory in prepubescent children. Design: Participants aged 7–9 y (n = 52) reported their dietary intake by using the Youth-Adolescent Food-Frequency Questionnaire and completed memory tasks designed to assess relational (hippocampal-dependent) and item (hippocampal-independent) memory. Performance on the memory tasks was assessed with both direct (accuracy) and indirect (eye movement) measures. Results: Partial correlations adjusted for body mass index showed a positive relation between relational memory accuracy and intake of omega-3 fatty acids and a negative relation of both relational and item memory accuracy with intake of SFAs. Potential confounding factors of age, sex, intelligence quotient, socioeconomic status, pubertal timing, and aerobic fitness (maximal oxygen volume) were not significantly related to any of the dietary intake measures. Eye movement measures of relational memory (preferential viewing to the target stimulus) showed a negative relation with intake of added sugar. Conclusions: SFA intake was negatively associated with both forms of memory, whereas omega-3 fatty acid intake was selectively positively associated with hippocampal-dependent relational memory. These findings are among the first to show a link between habitual dietary intake and cognitive health as pertaining to hippocampal function in childhood. The Fitness Improves Thinking Kids (FITKids) and FITKids2 trials were

  8. Dietary lipids are differentially associated with hippocampal-dependent relational memory in prepubescent children.

    Science.gov (United States)

    Baym, Carol L; Khan, Naiman A; Monti, Jim M; Raine, Lauren B; Drollette, Eric S; Moore, R Davis; Scudder, Mark R; Kramer, Arthur F; Hillman, Charles H; Cohen, Neal J

    2014-05-01

    Studies in rodents and older humans have shown that the hippocampus-a brain structure critical to relational/associative memory-has remarkable plasticity as a result of lifestyle factors (eg, exercise). However, the effect of dietary intake on hippocampal-dependent memory during childhood has remained unexamined. We investigated the cross-sectional relation of dietary components characteristic of the Western diet, including saturated fatty acids (SFAs), omega-3 (n-3) fatty acids, and refined sugar, with hippocampal-dependent relational memory in prepubescent children. Participants aged 7-9 y (n = 52) reported their dietary intake by using the Youth-Adolescent Food-Frequency Questionnaire and completed memory tasks designed to assess relational (hippocampal-dependent) and item (hippocampal-independent) memory. Performance on the memory tasks was assessed with both direct (accuracy) and indirect (eye movement) measures. Partial correlations adjusted for body mass index showed a positive relation between relational memory accuracy and intake of omega-3 fatty acids and a negative relation of both relational and item memory accuracy with intake of SFAs. Potential confounding factors of age, sex, intelligence quotient, socioeconomic status, pubertal timing, and aerobic fitness (maximal oxygen volume) were not significantly related to any of the dietary intake measures. Eye movement measures of relational memory (preferential viewing to the target stimulus) showed a negative relation with intake of added sugar. SFA intake was negatively associated with both forms of memory, whereas omega-3 fatty acid intake was selectively positively associated with hippocampal-dependent relational memory. These findings are among the first to show a link between habitual dietary intake and cognitive health as pertaining to hippocampal function in childhood. The Fitness Improves Thinking Kids (FITKids) and FITKids2 trials were registered at www.clinicaltrials.gov as NCT01334359 and NCT

  9. Hippocampal EEG and behaviour in dog. II. Hippocampal EEG correlates with elementary motor acts

    NARCIS (Netherlands)

    Arnolds, D.E.A.T.; Lopes da Silva, F.H.; Aitink, J.W.; Kamp, A.

    A positive correlation has been shown between the speed of forced stepping on a conveyor belt and the amplitude and frequency of the concomitant hippocampal EEG. Significant modulation in the spectral properties of the dog's hippocampal EEG has been found in relation to 3 elementary motor acts:

  10. Contribution of Hippocampal 5-HT3 Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats.

    Science.gov (United States)

    Wu, Zhong-Min; Yang, Li-Hua; Cui, Rong; Ni, Gui-Lian; Wu, Feng-Tian; Liang, Yong

    2017-05-01

    One of the hypotheses about the pathogenesis of posttraumatic stress disorder (PTSD) is the dysfunction of serotonin (5-HT) neurotransmission. While certain 5-HT receptor subtypes are likely critical for the symptoms of PTSD, few studies have examined the role of 5-HT 3 receptor in the development of PTSD, even though 5-HT 3 receptor is critical for contextual fear extinction and anxiety-like behavior. Therefore, we hypothesized that stimulation of 5-HT 3 receptor in the dorsal hippocampus (DH) could prevent hippocampal autophagy and the development of PTSD-like behavior in animals. To this end, we infused SR57227, selective 5-HT 3 agonist, into the DH after a single prolonged stress (SPS) treatment in rats. Three weeks later, we evaluated the effects of this pharmacological treatment on anxiety-related behaviors and extinction of contextual fear memory. We also accessed hippocampal autophagy and the expression of 5-HT 3A subunit, Beclin-1, LC3-I, and LC3-II