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Sample records for active hippocampal cultures

  1. Modulation of Network Activity in Dissociated Hippocampal Cultures by Enzymatic Digestion of Extracellular Matrix

    OpenAIRE

    Mukhina I.V.; Vedunova М.V.; Sakharnova Т.А.; Dityatev А.E.

    2012-01-01

    To investigate the role of extracellular matrix in spontaneous neuronal network activity, we used microelectrode array technology and enzymatic treatment of hippocampal culture with hyaluronidase, which digests the major component of extracellular matrix, hyaluronic acid. Studies were performed using hippocampal cells that were dissociated from embryonic С57ВL6 mice (E18) and plated on microelectrode arrays (MEAs). Our findings revealed that hyaluronidase promoted seizure-like activity during...

  2. Pilocarpine-induced seizure-like activity with increased BNDF and neuropeptide Y expression in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Poulsen, Frantz Rom; Jahnsen, Henrik; Blaabjerg, Morten;

    2002-01-01

    Organotypic hippocampal slice cultures were treated with the muscarinic agonist pilocarpine to study induced seizure-like activity and changes in neurotrophin and neuropeptide expression. For establishment of a seizure-inducing protocol, 2-week-old cultures derived from 6-8-day-old rats were...... by Western blot and ELISA. This BDNF increase correlated with increased neuropeptide Y immunoreactivity, known to accompany seizure activity. Addition of BDNF (200 ng/ml) to otherwise untreated cultures also upregulated NPY expression. The pilocarpine-induced seizure-like activity in hippocampal slice...

  3. NADPH oxidase mediates β-amyloid peptide-induced activation of ERK in hippocampal organotypic cultures

    Science.gov (United States)

    Serrano, Faridis; Chang, Angela; Hernandez, Caterina; Pautler, Robia G; Sweatt, J David; Klann, Eric

    2009-01-01

    Background Previous studies have shown that beta amyloid (Aβ) peptide triggers the activation of several signal transduction cascades in the hippocampus, including the extracellular signal-regulated kinase (ERK) cascade. In this study we sought to characterize the cellular localization of phosphorylated, active ERK in organotypic hippocampal cultures after acute exposure to either Aβ (1-42) or nicotine. Results We observed that Aβ and nicotine increased the levels of active ERK in distinct cellular localizations. We also examined whether phospho-ERK was regulated by redox signaling mechanisms and found that increases in active ERK induced by Aβ and nicotine were blocked by inhibitors of NADPH oxidase. Conclusion Our findings indicate that NADPH oxidase-dependent redox signaling is required for Aβ-induced activation of ERK, and suggest a similar mechanism may occur during early stages of Alzheimer's disease. PMID:19804648

  4. Seizure-like activity in hyaluronidase-treated dissociated hippocampal cultures

    Directory of Open Access Journals (Sweden)

    Maria eVedunova

    2013-09-01

    Full Text Available The extracellular matrix (ECM plays an important role in use-dependent synaptic plasticity. Hyaluronic acid (HA is the backbone of the neural ECM, which has been shown to modulate -amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA receptor mobility, paired-pulse depression, L-type voltage-dependent Ca2+ channel (L-VDCC activity, long-term potentiation and contextual fear conditioning. To investigate the role of HA in the development of spontaneous neuronal network activity, we used microelectrode array recording and Ca2+ imaging in hippocampal cultures enzymatically treated with hyaluronidase. Our findings revealed an appearance of epileptiform activity 9 days after hyaluronidase treatment. The treatment transformed the normal network firing bursts and Ca2+ oscillations into long-lasting superbursts and superoscillations with durations of 11-100 seconds. The changes in Ca2+ transients in hyaluronidase-treated neurons were more prominent then in astrocytes and preceded changes in electrical activity. The Ca2+ superoscillations could be suppressed by applying the L-VDCC blocker diltiazem, whereas the neuronal firing superbursts could be additionally suppressed by an 6-cyano-7-nitroquinoxaline-2,3-dione as an antagonist of AMPA/kainate receptors. These results suggest that changes in the expression of HA can be epileptogenic and that hyaluronidase treatment in vitro provides a robust model for the dissection of the underlying mechanisms.

  5. Rapid effect of stress concentration corticosterone on glutamate receptor and its subtype NMDA receptor activity in cultured hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    刘玲; 孙继虎; 王春安

    2003-01-01

    Objective:To study the rapid effect of glucocorticoids(GCs)on NMDA receptor activity in hippocampal neurons in stress and to elucidate its underlying probable membrane mechanisms.Methods:Whole-cell patch-clamp recording was used to assess the effect of stress concentration corticosterone(B)on the responses of cultured hippocampal neurons to glutamate and NMDA(N-methy-D-asparatic acid).To make clear the target of B,intracellular dialysis of B(10 μ mol/L)through patch pipette and extracellular application of bovine serum albumin-conjugated corticosterone(B-BSA,10 μmol/L)were carried out to observe their influence on peak amplitude of NMDA-evoked current.Results:B had a rapid,reversible and inhibitory effect on peak amplitude of GLU- or NMDA-evoked current in cultured hippocampal neurons.Furthermore,B-BSA had the inhibitory effect on INMDA as that of B,but intracellularly dialyzed B had no significant effect on INMDA.Conclusion:These results suggest that under the condition of stress,GCs may rapidly,negatively regulate excitatory synaptic receptors-glutamate receptors(GluRs),especially NMDA receptor(NMDAR)in central nervous system,which is mediated by rapid membrane mechanisms,but not by classical,genomic mechanisms.

  6. The regulation of M1 muscarinic acetylcholine receptor desensitization by synaptic activity in cultured hippocampal neurons1

    OpenAIRE

    Willets, Jonathon M.; Nelson, Carl P.; Nahorski, Stefan R; Challiss, R.A. John

    2007-01-01

    To better understand metabotropic/ionotropic integration in neurons we have examined the regulation of M1 muscarinic acetylcholine (mACh) receptor signalling in mature (> 14 days in vitro), synaptically-active hippocampal neurons in culture. Using a protocol where neurons are exposed to an EC50 concentration of the muscarinic agonist methacholine (MCh) prior to (R1), and following (R2) a desensitizing pulse of a high concentration of this agonist, we have found that the reduction in M1 mACh r...

  7. Loss of glutathione homeostasis associated with neuronal senescence facilitates TRPM2 channel activation in cultured hippocampal pyramidal neurons

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    Belrose Jillian C

    2012-04-01

    Full Text Available Abstract Background Glutathione (GSH plays an important role in neuronal oxidant defence. Depletion of cellular GSH is observed in neurodegenerative diseases and thereby contributes to the associated oxidative stress and Ca2+ dysregulation. Whether depletion of cellular GSH, associated with neuronal senescence, directly influences Ca2+ permeation pathways is not known. Transient receptor potential melastatin type 2 (TRPM2 is a Ca2+ permeable non-selective cation channel expressed in several cell types including hippocampal pyramidal neurons. Moreover, activation of TRPM2 during oxidative stress has been linked to cell death. Importantly, GSH has been reported to inhibit TRPM2 channels, suggesting they may directly contribute to Ca2+ dysregulation associated with neuronal senescence. Herein, we explore the relation between cellular GSH and TRPM2 channel activity in long-term cultures of hippocampal neurons. Results In whole-cell voltage-clamp recordings, we observe that TRPM2 current density increases in cultured pyramidal neurons over time in vitro. The observed increase in current density was prevented by treatment with NAC, a precursor to GSH synthesis. Conversely, treatment of cultures maintained for 2 weeks in vitro with L-BSO, which depletes GSH by inhibiting its synthesis, augments TRPM2 currents. Additionally, we demonstrate that GSH inhibits TRPM2 currents through a thiol-independent mechanism, and produces a 3.5-fold shift in the dose-response curve generated by ADPR, the intracellular agonist for TRPM2. Conclusion These results indicate that GSH plays a physiologically relevant role in the regulation of TRPM2 currents in hippocampal pyramidal neurons. This interaction may play an important role in aging and neurological diseases associated with depletion of GSH.

  8. Developmental and Activity-Dependent miRNA Expression Profiling in Primary Hippocampal Neuron Cultures

    NARCIS (Netherlands)

    M. van Spronsen (Myrrhe); E.Y. van Battum (Eljo); M. Kuijpers (Marijn); V.R. Vangoor (Vamshidhar); M.L. Rietman (M. Liset); J. Pothof (Joris); L.F. Gumy (Laura); W.F.J. van IJcken (Wilfred); A.S. Akhmanova (Anna); R.J. Pasterkamp (Jeroen); C.C. Hoogenraad (Casper)

    2013-01-01

    textabstractMicroRNAs (miRNAs) are evolutionarily conserved non-coding RNAs of ∼22 nucleotides that regulate gene expression at the level of translation and play vital roles in hippocampal neuron development, function and plasticity. Here, we performed a systematic and in-depth analysis of miRNA exp

  9. Proteasome Inhibition Triggers Activity-Dependent Increase in the Size of the Recycling Vesicle Pool in Cultured Hippocampal Neurons

    OpenAIRE

    Willeumier, Kristen; Pulst, Stefan M.; Schweizer, Felix E.

    2006-01-01

    The ubiquitin proteasome system, generally known for its function in protein degradation, also appears to play an important role in regulating membrane trafficking. A role for the proteasome in regulating presynaptic release and vesicle trafficking has been proposed for invertebrates, but it remains to be tested in mammalian presynaptic terminals. We used the fluorescent styrylpyridinium dye FM4-64 to visualize changes in the recycling pool of vesicles in hippocampal culture under pharmacolog...

  10. Addition of glutamate to serum free culture promotes recovery of electrical activity in adult hippocampal neurons in vitro

    OpenAIRE

    Edwards, Darin; Das, Mainak; Molnar, Peter; Hickman, James J.

    2010-01-01

    A long-term cell culture system utilizing normal adult hippocampal neurons would represent an important tool that could be useful in research on the mature brain, neurological disorders and age-related neurological diseases. Historically, in vitro neuronal systems are derived from embryonic rather than mature brain tissue, a practice predicated upon difficulties in supporting regeneration, functional recovery and long-term survival of adult neurons in vitro. A few studies have shown that neur...

  11. Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Zhi-ying LIN; Li-min CHEN; Jing ZHANG; Xiao-dong PAN; Yuan-gui ZHU; Qin-yong YE; Hua-pin HUANG; Xiao-chun CHEN

    2012-01-01

    Aim:To investigate the effect of ginsenoside Rb1 on voltage-gated calcium currents in cultured rat hippocampal neurons and the modulatory mechanism.Methods:Cultured hippocampal neurons were prepared from Sprague Dawley rat embryos.Whole-cell configuration of the patchclamp technique was used to record the voltage-gated calcium currents (VGCCs)from the hippocampal neurons,and the effect of Rb1 was examined.Results:Rb1 (2-100 μmol/L)inhibited VGCCs in a concentration-dependent manner,and the current was mostly recovered upon wash-out.The specific L-type Ca2+ channel inhibitor nifedipine (10 μmol/L)occluded Rb1-induced inhibition on VGCCs.Neither the selective N-type Ca2+ channel blocker ω-conotoxin-GVlA (1 μmoVL),nor the selective P/Q-type Ca2+ channel blocker ωo-agatoxin IVA (30 nmol/L)diminished Rb1-sensitive VGCCs.Rb1 induced a leftward shift of the steady-state inactivation curve of Ica to a negative potential without affecting its activation kinetics or reversal potential in the I-V curve.The inhibitory effect of Rb1 was neither abolished by the adenylyl cyclase activator forskolin (10 μmol/L),nor by the PKA inhibitor H-89 (10 μmol/L).Conclusion:Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels,without affecting the N-type or P/Q-type Ca2+ channels in hippocampal neurons,cAMP-PKA signaling pathway is not involved in this effect.

  12. Seizure-like activity in hyaluronidase-treated dissociated hippocampal cultures

    OpenAIRE

    Vedunova, Maria; Sakharnova, Tatiana; Mitroshina, Elena; Perminova, Maya; Pimashkin, Alexey; Zakharov, Yury; Dityatev, Alexander; Mukhina, Irina

    2013-01-01

    The extracellular matrix (ECM) plays an important role in use-dependent synaptic plasticity. Hyaluronic acid (HA) is the backbone of the neural ECM, which has been shown to modulate α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptor mobility, paired-pulse depression, L-type voltage-dependent Ca2+ channel (L-VDCC) activity, long-term potentiation and contextual fear conditioning. To investigate the role of HA in the development of spontaneous neuronal network activity, we used m...

  13. Age-Dependent Glutamate Induction of Synaptic Plasticity in Cultured Hippocampal Neurons

    Science.gov (United States)

    Ivenshitz, Miriam; Segal, Menahem; Sapoznik, Stav

    2006-01-01

    A common denominator for the induction of morphological and functional plasticity in cultured hippocampal neurons involves the activation of excitatory synapses. We now demonstrate massive morphological plasticity in mature cultured hippocampal neurons caused by a brief exposure to glutamate. This plasticity involves a slow, 70%-80% increase in…

  14. Agmatine increases proliferation of cultured hippocampal progenitor cells and hippocampal neurogenesis in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Yun-feng LI; Hong-xia CHEN; Ying LIU; You-zhi ZHANG; Yan-qin LIU; Jin LI

    2006-01-01

    Aim:To explore the mechanism of agmatine's antidepressant action.Methods: Male mice were subjected to a variety of unpredictable stressors on a daily basis over a 24-d period.The open-field behaviors of the mice were displayed and recorded using a Videomex-V image analytic system automatically.For bromodeoxyuridine (BrdU;thymidine analog as a marker for dividing cells) labeling,the mice were injected with BrdU (100 mg/kg,ip,twice per d for 2 d),and the hippocampal neurogenesis in stressed mice was measured by immunohistochemistry.The proliferation of cultured hippocampal progenitor cells from neonatal rats was determined by colorimetric assay (cell counting kit-8) and 3H-thymidine incorporation assay.Results:After the onset of chronic stress,the locomotor activity of the mice in the open field significantly decreased,while coadministration of agmatine 10 mg/kg (po) blocked it.Furthermore,the number of BrdU-labeled cells in the hippocampal dentate gyrus significantly decreased in chronically stressed mice, which was also blocked by chronic coadministration with agmatine 10 mg/kg (po). Four weeks after the BrdU injection, some of the new born cells matured and became neurons, as determined by double labeling for BrdU and neuron specific enolase (NSE), a marker for mature neurons.In vitro treatment with agmatine 0.1-10 μmo1/L for 3 d significantly increased the proliferation of the cultured hippocampal progenitor cells in a dose-dependent manner.Conclusion:We have found that agmatine increases proliferation of hippocampal progenitor cells in vitro and the hippocampal neurogenesis in vivo in chronically stressed mice.This may be one of the important mechanisms involved in agmatine's antidepressant action.

  15. Staining protocol for organotypic hippocampal slice cultures.

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    Gogolla, Nadine; Galimberti, Ivan; DePaola, Vincenzo; Caroni, Pico

    2006-01-01

    This protocol details a method to immunostain organotypic slice cultures from mouse hippocampus. The cultures are based on the interface method, which does not require special equipment, is easy to execute and yields slice cultures that can be imaged repeatedly, from the time of isolation at postnatal day 6-9 up to 6 months in vitro. The preserved tissue architecture facilitates the analysis of defined hippocampal synapses, cells and entire projections. Time-lapse imaging is based on transgenes expressed in the mice or on constructs introduced through transfection or viral vectors; it can reveal processes that develop over periods ranging from seconds to months. Subsequent to imaging, the slices can be processed for immunocytochemistry to collect further information about the imaged structures. This protocol can be completed in 3 d.

  16. HIV-1 Tat activates indoleamine 2,3 dioxygenase in murine organotypic hippocampal slice cultures in a p38 mitogen-activated protein kinase-dependent manner

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    Kelley Keith W

    2011-08-01

    Full Text Available Abstract Background We have established that activation of the tryptophan degrading enzyme indoleamine 2,3 dioxygenase (IDO mediates the switch from cytokine-induced sickness behavior to depressive-like behavior. Because human immunodeficiency virus type 1 (HIV-1 Tat protein causes depressive-like behavior in mice, we investigated its ability to activate IDO in organotypic hippocampal slice cultures (OHSCs derived from neonatal C57BL/6 mice. Methods Depressive-like behavior in C57BL/6J mice was assessed by the forced swim test. Expression of cytokines and IDO mRNA in OHSCs was measured by real-time RT-PCR and cytokine protein was measured by enzyme-linked immunosorbent assays (ELISAs. p38 MAPK phosphorylation was analyzed by western blot. Results Intracerebroventricular (i.c.v. administration of Tat (40 ng induced depressive-like behavior in the absence of sickness. Addition of Tat (40 ng/slice to the medium of OHSCs induced IDO steady-state mRNA that peaked at 6 h. This effect was potentiated by pretreatment with IFNγ. Tat also induced the synthesis and release of TNFα and IL-6 protein in the supernatant of the slices and increased expression of the inducible isoform of nitric oxide synthase (iNOS and the serotonin transporter (SERT. Tat had no effect on endogenous synthesis of IFNγ. To explore the mechanisms of Tat-induced IDO expression, slices were pretreated with the p38 mitogen-activated protein kinase (MAPK inhibitor SB 202190 for 30 min before Tat treatment. SB 202190 significantly decreased IDO expression induced by Tat, and this effect was accompanied by a reduction of Tat-induced expression of TNFα, IL-6, iNOS and SERT. Conclusion These data establish that Tat induces IDO expression via an IFNγ-independent mechanism that depends upon activation of p38 MAPK. Targeting IDO itself or the p38 MAPK signaling pathway could provide a novel therapy for comorbid depressive disorders in HIV-1-infected patients.

  17. Functional clustering in hippocampal cultures: relating network structure and dynamics

    International Nuclear Information System (INIS)

    In this work we investigate the relationship between gross anatomic structural network properties, neuronal dynamics and the resultant functional structure in dissociated rat hippocampal cultures. Specifically, we studied cultures as they developed under two conditions: the first supporting glial cell growth (high glial group), and the second one inhibiting it (low glial group). We then compared structural network properties and the spatio-temporal activity patterns of the neurons. Differences in dynamics between the two groups could be linked to the impact of the glial network on the neuronal network as the cultures developed. We also implemented a recently developed algorithm called the functional clustering algorithm (FCA) to obtain the resulting functional network structure. We show that this new algorithm is useful for capturing changes in functional network structure as the networks evolve over time. The FCA detects changes in functional structure that are consistent with expected dynamical differences due to the impact of the glial network. Cultures in the high glial group show an increase in global synchronization as the cultures age, while those in the low glial group remain locally synchronized. We additionally use the FCA to quantify the amount of synchronization present in the cultures and show that the total level of synchronization in the high glial group is stronger than in the low glial group. These results indicate an interdependence between the glial and neuronal networks present in dissociated cultures

  18. Localized gene transfer into organotypic hippocampal slice cultures and acute hippocampal slices

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Shen, H;

    1993-01-01

    Viral vectors derived from herpes simplex virus, type-1 (HSV), can transfer and express genes into fully differentiated, post-mitotic neurons. These vectors also transduce cells effectively in organotypic hippocampal slice cultures. Nanoliter quantities of a virus stock of HSVlac, an HSV vector...... effective and rapid. The titer of the HSVlac stocks was determined on NIH3T3 cells. Eighty-three percent of the beta-gal forming units successfully transduced beta-gal after microapplication to slice cultures. beta-Gal expression was detected as rapidly as 4 h after transduction into cultures of fibroblasts...... or hippocampal slices. The rapid expression of beta-gal by HSVlac allowed efficient transduction of acute hippocampal slices. Many genes have been transduced and expressed using HSV vectors; therefore, this microapplication method can be applied to many neurobiological questions....

  19. Central Administration of Lipopolysaccharide Induces Depressive-like Behavior in Vivo and Activates Brain Indoleamine 2,3 Dioxygenase In Murine Organotypic Hippocampal Slice Cultures

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    Kavelaars Annemieke

    2010-08-01

    Full Text Available Abstract Background Transient stimulation of the innate immune system by an intraperitoneal injection of lipopolysaccharide (LPS activates peripheral and central expression of the tryptophan degrading enzyme indoleamine 2,3 dioxygenase (IDO which mediates depressive-like behavior. It is unknown whether direct activation of the brain with LPS is sufficient to activate IDO and induce depressive-like behavior. Methods Sickness and depressive-like behavior in C57BL/6J mice were assessed by social exploration and the forced swim test, respectively. Expression of cytokines and IDO mRNA was measured by real-time RT-PCR and cytokine protein was measured by enzyme-linked immunosorbent assays (ELISAs. Enzymatic activity of IDO was estimated as the amount of kynurenine produced from tryptophan as determined by high pressure liquid chromatography (HPLC with electrochemical detection. Results Intracerebroventricular (i.c.v. administration of LPS (100 ng increased steady-state transcripts of TNFα, IL-6 and the inducible isoform of nitric oxide synthase (iNOS in the hippocampus in the absence of any change in IFNγ mRNA. LPS also increased IDO expression and induced depressive-like behavior, as measured by increased duration of immobility in the forced swim test. The regulation of IDO expression was investigated using in situ organotypic hippocampal slice cultures (OHSCs derived from brains of newborn C57BL/6J mice. In accordance with the in vivo data, addition of LPS (10 ng/ml to the medium of OHSCs induced steady-state expression of mRNA transcripts for IDO that peaked at 6 h and translated into increased IDO enzymatic activity within 8 h post-LPS. This activation of IDO by direct application of LPS was preceded by synthesis and secretion of TNFα and IL-6 protein and activation of iNOS while IFNγ expression was undetectable. Conclusion These data establish that activation of the innate immune system in the brain is sufficient to activate IDO and induce

  20. Persistent Gliosis Interferes with Neurogenesis in Organotypic Hippocampal Slice Cultures.

    Science.gov (United States)

    Gerlach, Johannes; Donkels, Catharina; Münzner, Gert; Haas, Carola A

    2016-01-01

    Neurogenesis in the adult hippocampus has become an intensively investigated research topic, as it is essential for proper hippocampal function and considered to bear therapeutic potential for the replacement of pathologically lost neurons. On the other hand, neurogenesis itself is frequently affected by CNS insults. To identify processes leading to the disturbance of neurogenesis, we made use of organotypic hippocampal slice cultures (OHSC), which, for unknown reasons, lose their neurogenic potential during cultivation. In the present study, we show by BrdU/Prox1 double-immunostaining that the generation of new granule cells drops by 90% during the first week of cultivation. Monitoring neurogenesis dynamically in OHSC from POMC-eGFP mice, in which immature granule cells are endogenously labeled, revealed a gradual decay of the eGFP signal, reaching 10% of initial values within 7 days of cultivation. Accordingly, reverse transcription quantitative polymerase chain reaction analysis showed the downregulation of the neurogenesis-related genes doublecortin and Hes5, a crucial target of the stem cell-maintaining Notch signaling pathway. In parallel, we demonstrate a strong and long-lasting activation of astrocytes and microglial cells, both, morphologically and on the level of gene expression. Enhancement of astroglial activation by treating OHSC with ciliary neurotrophic factor accelerated the loss of neurogenesis, whereas treatment with indomethacin or an antagonist of the purinergic P2Y12 receptor exhibited potent protective effects on the neurogenic outcome. Therefore, we conclude that OHSC rapidly lose their neurogenic capacity due to persistent inflammatory processes taking place after the slice preparation. As inflammation is also considered to affect neurogenesis in many CNS pathologies, OHSC appear as a useful tool to study this interplay and its molecular basis. Furthermore, we propose that modification of glial activation might bear the therapeutic potential

  1. Persistent gliosis interferes with neurogenesis in organotypic hippocampal slice cultures

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    Johannes eGerlach

    2016-05-01

    Full Text Available Neurogenesis in the adult hippocampus has become an intensively investigated research topic, as it is essential for proper hippocampal function and considered to bear therapeutic potential for the replacement of pathologically lost neurons. On the other hand, neurogenesis itself is frequently affected by CNS insults. To identify processes leading to the disturbance of neurogenesis, we made use of organotypic hippocampal slice cultures (OHSC, which, for unknown reasons, lose their neurogenic potential during cultivation. In the present study, we show by BrdU/Prox1 double-immunostaining that the generation of new granule cells drops by 90% during the first week of cultivation. Monitoring neurogenesis dynamically in OHSC from POMC-eGFP mice, in which immature granule cells are endogenously labeled, revealed a gradual decay of the eGFP signal, reaching 10% of initial values within seven days of cultivation. Accordingly, RT-qPCR analysis showed the downregulation of the neurogenesis-related genes doublecortin and Hes5, a crucial target of the stem cell-maintaining Notch signaling pathway. In parallel, we demonstrate a strong and long-lasting activation of astrocytes and microglial cells, both, morphologically and on the level of gene expression. Enhancement of astroglial activation by treating OHSC with ciliary neurotrophic factor (CNTF accelerated the loss of neurogenesis, whereas treatment with indomethacin or an antagonist of the purinergic P2Y12 receptor exhibited potent protective effects on the neurogenic outcome. Therefore, we conclude that OHSC rapidly lose their neurogenic capacity due to persistent inflammatory processes taking place after the slice preparation. As inflammation is also considered to affect neurogenesis in many CNS pathologies, OHSC appear as a useful tool to study this interplay and its molecular basis. Furthermore, we propose that modification of glial activation might bear the therapeutic potential of enabling

  2. Characterization of the in vitro propagation of epileptiform electrophysiological activity in organotypic hippocampal slice cultures coupled to 3D microelectrode arrays

    DEFF Research Database (Denmark)

    Pisciotta, Marzia; Morgavi, Giovanna; Jahnsen, Henrik

    2010-01-01

    Dynamic aspects of the propagation of epileptiform activity have so far received little attention. With the aim of providing new insights about the spatial features of the propagation of epileptic seizures in the nervous system, we studied in vitro the initiation and propagation of traveling...... in hippocampus in vivo. Feng Z, Durand DM. J Neurophysiol. 2005 Mar; 93(3):1158-64. Epub 2004 Oct 20.Chloride-cotransport blockade desynchronizes neuronal discharge in the "epileptic" hippocampal slice. [J Neurophysiol. 2000] Chloride-cotransport blockade desynchronizes neuronal discharge in the "epileptic...

  3. Ethanol induces MAP2 changes in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Zimmer, J

    1998-01-01

    Microtubule-associated protein 2 (MAP2) and neuron-specific protein (NeuN) immunostains were used to demonstrate neurotoxic effects in mature hippocampal slice cultures exposed to ethanol (50, 100, 200 mM) for 4 weeks. At the low dose the density of MAP2 immunostaining in the dentate molecular...... layer was 118% of the control cultures, with no detectable changes in CA1 and CA3. At 100 mM no changes were detected, while 200 mM ethanol significantly reduced the MAP2 density in both dentate (19%) and hippocampal dendritic fields (CA3, 52%; CA1, 55%). At this dose NeuN staining showed considerable...... loss of CA3 pyramidal cells and moderate loss of dentate granule cells, as seen in vivo. The results indicate that brain slice cultures combined with immunostaining for cytoskeleton and neuronal markers can be used for studies of ethanol and organic solvent neurotoxicity....

  4. Trimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Gramsbergen, J B; Fonnum, F;

    1998-01-01

    The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model for neurotoxico......The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model...... for neurotoxicological studies, including further studies of neurotoxic mechanisms of TMT. Four-week-old cultures, derived from 7-day-old donor rats and grown in serum-free medium, were exposed to TMT (0.5-100 microM) for 24 h followed by 24 h in normal medium. TMT-induced neurodegeneration was then monitored by (a...

  5. Inhibition of glycine-activated current by melatonin in cultured rat hippocampal neurons%松果体素抑制大鼠海马神经元甘氨酸激活的全细胞电流

    Institute of Scientific and Technical Information of China (English)

    程新萍; 开远忠; 吴旭; 刘雅静; 周江宁

    2012-01-01

    目的 研究松果体素对培养的大鼠海马神经元甘氨酸激活的全细胞电流(Igly)的调控.方法 在培养的大鼠海马神经元上,采用全细胞膜片钳技术,研究松果体素对甘氨酸激活的全细胞电流的调控.结果 松果体素以浓度依赖的方式可逆地抑制Igly,并且这种抑制作用是非竞争性的,松果体素的抑制作用没有特异的亚基选择性.结论 松果体素能以非竞争的方式直接抑制甘氨酸受体介导的电流,这种抑制作用可能对海马区域神经网络的兴奋性产生影响.%Aim To investigate the effect of melatonin on the glycine-activated current ( Igly ) in cultured rat hippocampal neurons. Method Whole-cell patch-clamp technique was used. Result Melatonin rapidly and reversibly inhibited the amplitude of glycine-activated current mediated by native glycine receptors and recombinant al-a2-a3-and alp-glycine receptors. In cultured rat hippocampal neurons, melatonin inhibited the glycine-activated current in a dose-dependentmanner. Furthermore, melatonin noncompetitively inhibited the Igly Conclusion Melatonin can directly depress GlyR-mediated currents in a non-competitive and subunit-independent manner, suggesting that melatonin may modulate glycinergic transmission and hippocampal network activity.

  6. A calcium-permeable cGMP-activated cation conductance in hippocampal neurons

    Science.gov (United States)

    Leinders-Zufall, T.; Rosenboom, H.; Barnstable, C. J.; Shepherd, G. M.; Zufall, F.

    1995-01-01

    Whole-cell patch clamp recordings detected a previously unidentified cGMP-activated membrane conductance in cultured rat hippocampal neurons. This conductance is nonselectively permeable for cations and is completely but reversibly blocked by external Cd2+. The Ca2+ permeability of the hippocampal cGMP-activated conductance was examined in detail, indicating that the underlying ion channels display a high relative permeability for Ca2+. The results indicate that hippocampal neurons contain a cGMP-activated membrane conductance that has some properties similar to the cyclic nucleotide-gated channels previously shown in sensory receptor cells and retinal neurons. In hippocampal neurons this conductance similarly could mediate membrane depolarization and Ca2+ fluxes in response to intracellular cGMP elevation.

  7. The structural development of primary cultured hippocampal neurons on a graphene substrate.

    Science.gov (United States)

    He, Zuhong; Zhang, Shasha; Song, Qin; Li, Wenyan; Liu, Dong; Li, Huawei; Tang, Mingliang; Chai, Renjie

    2016-10-01

    The potential of graphene-based nanomaterials as a neural interfacing material for neural repair and regeneration remains poorly understood. In the present study, the response to the graphene substrate by neurons was determined in a hippocampal culture model. The results revealed the growth and maturation of hippocampal cultures on graphene substrates were significantly improved compared to the commercial control. In details, graphene promoted growth cone growth and microtubule formation inside filopodia 24h after seeding as evidenced by a higher average number of filopodia emerging from growth cones, a longer average length of filopodia, and a larger growth cone area. Graphene also significantly boosted neurite sprouting and outgrowth. The dendritic length, the number of branch points, and the dendritic complex index were significantly improved on the graphene substrate during culture. Moreover, the spine density was enhanced and the maturation of dendritic spines from thin to stubby spines was significantly promoted on graphene at 21 days after seeding. Lastly, graphene significantly elevated the synapse density and synaptic activity in the hippocampal cultures. The present study highlights graphene's potential as a neural interfacing material for neural repair and regeneration and sheds light on the future biomedical applications of graphene-based nanomaterials. PMID:27395037

  8. Neuroprotective effect of piperine on primarily cultured hippocampal neurons.

    Science.gov (United States)

    Fu, Min; Sun, Zhao-Hui; Zuo, Huan-Cong

    2010-01-01

    It was previously reported that piperine (PIP) significantly blocks convulsions induced by intracerebroventricular injection of threshold doses of kainate, but had no or only slight effects on convulsions induced by L-glutamate, N-methyl-D-aspartate and guanidinosuccinate. In traditional Chinese medicine, black pepper has been used for epileptic treatment; however, the exact mechanism is still unclear. We reported here in that appropriate concentration of PIP effectively inhibites the synchronized oscillation of intracellular calcium in rat hippocampal neuronal networks and represses spontaneous synaptic activities in terms of spontaneous synaptic currents (SSC) and spontaneous excitatory postsynaptic currents (sEPSC). Moreover, pretreatment with PIP expects protective effect on glutamate-induced decrease of cell viability and apoptosis of hippocampal neurons. These data suggest that the neuroprotective effects of PIP might be associated with suppression of synchronization of neuronal networks, presynaptic glutamic acid release, and Ca(2+) overloading.

  9. Synaptic network activity induces neuronal differentiation of adult hippocampal precursor cells through BDNF signaling

    Directory of Open Access Journals (Sweden)

    Harish Babu

    2009-09-01

    Full Text Available Adult hippocampal neurogenesis is regulated by activity. But how do neural precursor cells in the hippocampus respond to surrounding network activity and translate increased neural activity into a developmental program? Here we show that long-term potential (LTP-like synaptic activity within a cellular network of mature hippocampal neurons promotes neuronal differentiation of newly generated cells. In co-cultures of precursor cells with primary hippocampal neurons, LTP-like synaptic plasticity induced by addition of glycine in Mg2+-free media for 5 min, produced synchronous network activity and subsequently increased synaptic strength between neurons. Furthermore, this synchronous network activity led to a significant increase in neuronal differentiation from the co-cultured neural precursor cells. When applied directly to precursor cells, glycine and Mg2+-free solution did not induce neuronal differentiation. Synaptic plasticity-induced neuronal differentiation of precursor cells was observed in the presence of GABAergic neurotransmission blockers but was dependent on NMDA-mediated Ca2+ influx. Most importantly, neuronal differentiation required the release of brain-derived neurotrophic factor (BDNF from the underlying substrate hippocampal neurons as well as TrkB receptor phosphorylation in precursor cells. This suggests that activity-dependent stem cell differentiation within the hippocampal network is mediated via synaptically evoked BDNF signaling.

  10. Potent activity of nobiletin-rich Citrus reticulata peel extract to facilitate cAMP/PKA/ERK/CREB signaling associated with learning and memory in cultured hippocampal neurons: identification of the substances responsible for the pharmacological action.

    Science.gov (United States)

    Kawahata, Ichiro; Yoshida, Masaaki; Sun, Wen; Nakajima, Akira; Lai, Yanxin; Osaka, Naoya; Matsuzaki, Kentaro; Yokosuka, Akihito; Mimaki, Yoshihiro; Naganuma, Akira; Tomioka, Yoshihisa; Yamakuni, Tohru

    2013-10-01

    cAMP/PKA/ERK/CREB signaling linked to CRE-mediated transcription is crucial for learning and memory. We originally found nobiletin as a natural compound that stimulates this intracellular signaling and exhibits anti-dementia action in animals. Citrus reticulata or C. unshiu peels are employed as "chinpi" and include a small amount of nobiletin. We here provide the first evidence for beneficial pharmacological actions on the cAMP/PKA/ERK/CREB cascade of extracts from nobiletin-rich C.reticulata peels designated as Nchinpi, the nobiletin content of which was 0.83 ± 0.13% of the dry weight or 16-fold higher than that of standard chinpi extracts. Nchinpi extracts potently facilitated CRE-mediated transcription in cultured hippocampal neurons, whereas the standard chinpi extracts showed no such activity. Also, the Nchinpi extract, but not the standard chinpi extract, stimulated PKA/ERK/CREB signaling. Interestingly, treatment with the Nchinpi extract at the concentration corresponding to approximately 5 μM nobiletin more potently facilitated CRE-mediated transcriptional activity than did 30 μM nobiletin alone. Consistently, sinensetin, tangeretin, 6-demethoxynobiletin, and 6-demethoxytangeretin were also identified as bioactive substances in Nchinpi that facilitated the CRE-mediated transcription. Purified sinensetin enhanced the transcription to a greater degree than nobiletin. Furthermore, samples reconstituted with the four purified compounds and nobiletin in the ratio of each constituent's content in the extract showed activity almost equal to that of the Nchinpi extract to stimulate CRE-mediated transcription. These findings suggest that above four compounds and nobiletin in the Nchinpi extract mainly cooperated to facilitate potently CRE-mediated transcription linked to the upstream cAMP/PKA/ERK/CREB pathway in hippocampal neurons. PMID:23588349

  11. PACAP enhances axon outgrowth in cultured hippocampal neurons to a comparable extent as BDNF.

    Directory of Open Access Journals (Sweden)

    Katsuya Ogata

    Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP exerts neurotrophic activities including modulation of synaptic plasticity and memory, hippocampal neurogenesis, and neuroprotection, most of which are shared with brain-derived neurotrophic factor (BDNF. Therefore, the aim of this study was to compare morphological effects of PACAP and BDNF on primary cultured hippocampal neurons. At days in vitro (DIV 3, PACAP increased neurite length and number to similar levels by BDNF, but vasoactive intestinal polypeptide showed much lower effects. In addition, PACAP increased axon, but not dendrite, length, and soma size at DIV 3 similarly to BDNF. The PACAP antagonist PACAP6-38 completely blocked the PACAP-induced increase in axon, but not dendrite, length. Interestingly, the BDNF-induced increase in axon length was also inhibited by PACAP6-38, suggesting a mechanism involving PACAP signaling. K252a, a TrkB receptor inhibitor, inhibited axon outgrowth induced by PACAP and BDNF without affecting dendrite length. These results indicate that in primary cultured hippocampal neurons, PACAP shows morphological actions via its cognate receptor PAC1, stimulating neurite length and number, and soma size to a comparable extent as BDNF, and that the increase in total neurite length is ascribed to axon outgrowth.

  12. Influence of Ginkgo Biloba extract on beta-secretase in rat hippocampal neuronal cultures following chronic hypoxic and hypoglycemic conditions

    Institute of Scientific and Technical Information of China (English)

    Xueneng Guan; Fuling Yan

    2008-01-01

    BACKGROUND: Preparation of Ginkgo leaf has been widely used to improve cognitive deficits and dementia, in particular in Alzheimer's disease patients. However, the precise mechanism of action of Ginkgo leaf remains unclear.OBJECTIVE: To explore the effect of Ginkgo Biloba extract (Egb761), Ginaton, on β-secretase expression in rat hippocampal neuronal cultures following chronic hypoxic and hypoglycemic conditions.DESIGN, TIME AND SETTNG: Completely by randomized, grouping study. The experiment was performed at the Laboratory of Molecular Imaging, Southeast University between August 2006 and August 2007.MATERIALS: A total of 128 Wistar rats aged 24 hours were selected, and hippocampal neurons were harvested for primary cultures.METHODS: On day 7, primary hippocampal neuronal cultures were treated with Egb761 (0, 25, 50, 100, 150, and 200 μ g/mL) under hypoxic/hypoglycemic or hypoglycemic culture conditions for 12, 24, and 36 hours, respectively. Hippocampal neurons cultured in primary culture medium served as control.MAIN OUTCOME MEASURES: Cell viability was assayed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT); fluorescence detection of β-secretase activity was performed; Western Blot was used to measure β -secretase expression.RESULTS: Cell viability under hypoxic/hypoglycemic or hypoglycemic culture conditions was significantly less than control cells (P 25 μ g/mL Egb761 induced greater cell viability (P 0.05). Α -secretase activity was increased after 12 hours in hypoxic/hypoglycemic culture (P 0.05). Β -secretase activity was greater after 12, 24, and 36 hours in hypoxic/hypoglycemic culture conditions, compared with control conditions (P < 0.05). Β-secretase activity was significantly decreased in neurons treated with Egb761 for 12, 24, or 36 hours, compared with the hypoxic/hypoglycemic group (P < 0.05).β-secretase protein expression was significantly up-regulated in neurons cultured in hypoxic/hypoglycemic conditions for

  13. Glutamate receptor antagonists and growth factors modulate dentate granule cell neurogenesis in organotypic, rat hippocampal slice cultures

    DEFF Research Database (Denmark)

    Poulsen, Frantz Rom; Blaabjerg, Morten; Montero, Maria;

    2005-01-01

    Generation of dentate granule cells and its modulation by glutamate receptor antagonists, growth factors and pilocarpine-induced seizure-like activity was investigated in rat hippocampal slice cultures derived from 1-week-old rats and grown for 2 weeks. Focussing on the dentate granule cell layer...

  14. Downregulation of Transketolase Activity Is Related to Inhibition of Hippocampal Progenitor Cell Proliferation Induced by Thiamine Deficiency

    OpenAIRE

    Yanling Zhao; Yiying Wu; Haolu Hu; Jinghui Cai; Min Ning; Xiushi Ni; Chunjiu Zhong

    2014-01-01

    In animal experiments, hippocampal neurogenesis and the activity of thiamine-dependent transketolase decrease markedly under conditions of thiamine deficiency. To further investigate the effect of thiamine deficiency on the proliferation of hippocampal progenitor cells (HPCs) and the potential mechanisms involved in this effect, we cultured HPCs in vitro in the absence of thiamine and found that proliferation and transketolase activity were both significantly repressed. Furthermore, specific ...

  15. Spontaneous Plasticity of Multineuronal Activity Patterns in Activated Hippocampal Networks

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    Atsushi Usami

    2008-01-01

    Full Text Available Using functional multineuron imaging with single-cell resolution, we examined how hippocampal networks by themselves change the spatiotemporal patterns of spontaneous activity during the course of emitting spontaneous activity. When extracellular ionic concentrations were changed to those that mimicked in vivo conditions, spontaneous activity was increased in active cell number and activity frequency. When ionic compositions were restored to the control conditions, the activity level returned to baseline, but the weighted spatial dispersion of active cells, as assessed by entropy-based metrics, did not. Thus, the networks can modify themselves by altering the internal structure of their correlated activity, even though they as a whole maintained the same level of activity in space and time.

  16. Ghrelin regulates cell cycle-related gene expression in cultured hippocampal neural stem cells.

    Science.gov (United States)

    Chung, Hyunju; Park, Seungjoon

    2016-08-01

    We have previously demonstrated that ghrelin stimulates the cellular proliferation of cultured adult rat hippocampal neural stem cells (NSCs). However, little is known about the molecular mechanisms by which ghrelin regulates cell cycle progression. The purpose of this study was to investigate the potential effects of ghrelin on cell cycle regulatory molecules in cultured hippocampal NSCs. Ghrelin treatment increased proliferation assessed by CCK-8 proliferation assay. The expression levels of proliferating cell nuclear antigen and cell division control 2, well-known cell-proliferating markers, were also increased by ghrelin. Fluorescence-activated cell sorting analysis revealed that ghrelin promoted progression of cell cycle from G0/G1 to S phase, whereas this progression was attenuated by the pretreatment with specific inhibitors of MEK/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/Akt, mammalian target of rapamycin, and janus kinase 2/signal transducer and activator of transcription 3. Ghrelin-induced proliferative effect was associated with increased expression of E2F1 transcription factor in the nucleus, as determined by Western blotting and immunofluorescence. We also found that ghrelin caused an increase in protein levels of positive regulators of cell cycle, such as cyclin A and cyclin-dependent kinase (CDK) 2. Moreover, p27(KIP1) and p57(KIP2) protein levels were reduced when cell were exposed to ghrelin, suggesting downregulation of CDK inhibitors may contribute to proliferative effect of ghrelin. Our data suggest that ghrelin targets both cell cycle positive and negative regulators to stimulate proliferation of cultured hippocampal NSCs. PMID:27325242

  17. MEK inhibitor PD98059 acutely inhibits synchronized spontaneous Ca2+ oscillations in cultured hippocampal networks

    Institute of Scientific and Technical Information of China (English)

    Yan-fang RUI; Zhao-hui SUN; Jia-ping GU; Zhong-hua SHENG; Xiang-ping HE; Zuo-ping XIE

    2006-01-01

    Aim: To investigate the changes in synchronized spontaneous Ca2+ oscillations induced by mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 at different concentrations in cultured hippocampal network. Methods: Hippocampal neurons in culture for 1-2 weeks were used for this study. Spontaneous synaptic activities of these hippocampal neurons were examined by Ca2+ imaging using calcium-sensitive dye. MEK inhibitor PD98059 (10,30, and 60 μmol/L) and SB202474 (10 and 60 μmol/L), a negative control for mitogen-activated protein kinase (MAPK) cascade study, were applied to the cells under the microscope while imaging was taking place. Results: PD98059 at a lower concentration of 10 μmol/L had little effect on the Ca2+ oscillation. At the higher concentration of 30 μmol/L, 5 min after application of PD98059, the spike frequency was decreased to 25.38%±7.40% (mean±SEM, n=16, F<0.01 vs medium control) of that of the control period. At an even higher concentration of 60 μmol/L, 5 min after application of PD98059, the spike frequency was decreased to 14.53%±5.34% (mean±SEM, n=16, P<0.01 vs medium control) of that of the control period. The spike amplitude underwent a corresponding decrease. However, the negative control SB202474 at concentrations of 10 and 60 μmol/L had little inhibition effect on the Ca2+ oscillation. Conclusion: These results indicate that PD98059 inhibits synchronized spontaneous Ca2+ oscillation through inhibition of MEK, which hints that the MAPK cascade is required to maintain synchronized spontaneous Ca2+ oscillation.

  18. BDNF downregulates 5-HT(2A) receptor protein levels in hippocampal cultures

    DEFF Research Database (Denmark)

    Trajkovska, V; Santini, M A; Marcussen, Anders Bue;

    2009-01-01

    Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT(2A)) have been related to depression pathology. Specific 5-HT(2A) receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT(2A) receptor level. Here we show a direct effect of BDNF...... on 5-HT(2A) receptor protein levels in primary hippocampal neuronal and mature hippocampal organotypic cultures exposed to different BDNF concentrations for either 1, 3, 5 or 7 days. In vivo effects of BDNF on hippocampal 5-HT(2A) receptor levels were further corroborated in (BDNF +/-) mice...... with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50ng/mL BDNF resulted in downregulation of 5-HT(2A), but not of 5-HT(1A), receptor protein levels. The BDNF-associated downregulation of 5-HT(2A) receptor levels was also observed in mature hippocampal organotypic cultures...

  19. Perampanel inhibition of AMPA receptor currents in cultured hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Chao-Yin Chen

    Full Text Available Perampanel is an aryl substituted 2-pyridone AMPA receptor antagonist that was recently approved as a treatment for epilepsy. The drug potently inhibits AMPA receptor responses but the mode of block has not been characterized. Here the action of perampanel on AMPA receptors was investigated by whole-cell voltage-clamp recording in cultured rat hippocampal neurons. Perampanel caused a slow (τ∼1 s at 3 µM, concentration-dependent inhibition of AMPA receptor currents evoked by AMPA and kainate. The rates of block and unblock of AMPA receptor currents were 1.5×105 M-1 s-1 and 0.58 s-1, respectively. Perampanel did not affect NMDA receptor currents. The extent of block of non-desensitizing kainate-evoked currents (IC50, 0.56 µM was similar at all kainate concentrations (3-100 µM, demonstrating a noncompetitive blocking action. Parampanel did not alter the trajectory of AMPA evoked currents indicating that it does not influence AMPA receptor desensitization. Perampanel is a selective negative allosteric AMPA receptor antagonist of high-affinity and slow blocking kinetics.

  20. Hippocampal unit activity during classical aversive and appetitive conditioning.

    Science.gov (United States)

    Segal, M; Disterhoft, J F; Olds, J

    1972-02-18

    Rats were trained with a tone being followed by either food or electric shock, on alternate days. Unit activity during application of the conditioned stimulus was recorded from the dorsal hippocampus. The results indicate differentiation of the hippocampal system. Dentate units respond by augmentation to a conditioned stimulus which leads to food and by inhibition to the same stimulus when it precedes electric shock. The hippocampus proper responds by augmentation in both situations. The intensity of the hippocampal response to the conditioned stimulus on the first day of training is higher if the unconditioned stimulus is food than if it is electric shock. These data cast light on the functions of the dorsal dentate-hippocampal connections and the hippocampus proper during aversive and appetitive conditioning.

  1. Hyperexcitability and cell loss in kainate-treated hippocampal slice cultures

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Casaccia-Bonnefil, P; Stelzer, A;

    1993-01-01

    Loss of hippocampal interneurons has been reported in patients with severe temporal lobe epilepsy and in animals treated with kainate. We investigated the relationship between KA induced epileptiform discharge and loss of interneurons in hippocampal slice cultures. Application of KA (1 microM) pr......-like immunoreactive (PV-I) interneurons preceded loss of somatostatin-like immunoreactive (SS-I) interneurons suggesting a different time course of KA neurotoxicity in these subpopulations of interneurons....

  2. Erythropoietin improves synaptic transmission during and following ischemia in rat hippocampal slice cultures.

    Science.gov (United States)

    Weber, Astrid; Maier, Rolf F; Hoffmann, Ulrike; Grips, Martin; Hoppenz, Marc; Aktas, Ayse G; Heinemann, Uwe; Obladen, Michael; Schuchmann, Sebastian

    2002-12-27

    Erythropoietin (EPO) prevents neuronal damage following ischemic, metabolic, and excitotoxic stress. In this study evoked extracellular field potentials (FP) were used to investigate the effect of EPO on synaptic transmission in hippocampal slice cultures. EPO treated cultured slices (40 units/ml for 48 h) showed significantly increased FP during and following oxygen and glucose deprivation compared with untreated control slices. The addition of the Jak2 inhibitor AG490 (50 microM for 48 h) blocked the EPO effect. These data suggest that EPO improves synaptic transmission during and following ischemia in hippocampal slice cultures.

  3. Synaptic and extrasynaptic γ-aminobutyric acid type A receptor clusters in rat hippocampal cultures during development

    OpenAIRE

    Scotti, Alessandra L.; Reuter, Harald

    2001-01-01

    We have simultaneously measured the expression of postsynaptic γ-aminobutyric acid type A (GABAA) receptor clusters and of presynaptic boutons in neonatal rat hippocampal cultures between days 1 and 30. GABAA receptors were labeled with antibodies recognizing the extracellular domains of β2/3 and γ2 subunits. Boutons were visualized by activity-dependent uptake of the styryl dye FM4-64, or by antibodies against the presynaptic vesicular protein SV2 or the GABA-synt...

  4. Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons.

    Science.gov (United States)

    Morte, Maria I; Carreira, Bruno P; Falcão, Maria J; Ambrósio, António F; Soares-da-Silva, Patrício; Araújo, Inês M; Carvalho, Caetana M

    2013-12-01

    In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic pathways, such as extracellular-regulated kinase (ERK1/2), Akt and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). We found that neither ESL nor its metabolites, CBZ or LTG, up to 0.3mM, for 24h of exposure, decreased cell viability. OXC was the most toxic drug decreasing cell viability in a concentration-dependent manner, leading to activation of caspase-3 and PARP cleavage. VPA caused the appearance of the apoptotic markers, but did not alter cell viability. ESL, S-Lic and OXC decreased the levels of phospho-ERK1/2 and of phospho-Akt, when compared to basal levels, whereas CBZ decreased phospho-SAPK/JNK and phospho-Akt levels. LTG and VPA increased the phosphorylation levels of SAPK/JNK. These results suggest that ESL and its main metabolite S-Lic, as well as CBZ, LTG and VPA, are less toxic to hippocampal neurons than OXC, which was the most toxic agent. PMID:24055897

  5. Morphological assessment of neurite outgrowth in hippocampal neuron-astrocyte co-cultures.

    Science.gov (United States)

    Giordano, Gennaro; Costa, Lucio G

    2012-05-01

    Neurite outgrowth is a fundamental event in brain development, as well as in regeneration of damaged neurons. Astrocytes play a major role in neuritogenesis, by expressing and releasing factors that facilitate neurite outgrowth, such as extracellular matrix proteins, and factors that can inhibit neuritogenesis, such as the chondroitin sulfate proteoglycan neurocan. In this unit we describe a noncontact co-culture system of hippocampal neurons and cortical (or hippocampal) astrocytes for measurement of neurite outgrowth. Hippocampal pyramidal neurons are plated on glass coverslips, which are inverted onto an astrocyte feeder layer, allowing exposure of neurons to astrocyte-derived factors without direct contact between these two cell types. After co-culture, neurons are stained and photographed, and processes are assessed morphologically using Metamorph software. This method allows exposing astrocytes to various agents before co-culture in order to assess how these exposures may influence the ability of astrocytes to foster neurite outgrowth. PMID:22549268

  6. Full Length Bid is sufficient to induce apoptosis of cultured rat hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Ward Manus W

    2007-02-01

    Full Text Available Abstract Background Bcl-2 homology domain (BH 3-only proteins are pro-apoptotic proteins of the Bcl-2 family that couple stress signals to the mitochondrial cell death pathways. The BH3-only protein Bid can be activated in response to death receptor activation via caspase 8-mediated cleavage into a truncated protein (tBid, which subsequently translocates to mitochondria and induces the release of cytochrome-C. Using a single-cell imaging approach of Bid cleavage and translocation during apoptosis, we have recently demonstrated that, in contrast to death receptor-induced apoptosis, caspase-independent excitotoxic apoptosis involves a translocation of full length Bid (FL-Bid from the cytosol to mitochondria. We induced a delayed excitotoxic cell death in cultured rat hippocampal neurons by a 5-min exposure to the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 300 μM. Results Western blot experiments confirmed a translocation of FL-Bid to the mitochondria during excitotoxic apoptosis that was associated with the release of cytochrome-C from mitochondria. These results were confirmed by immunofluorescence analysis of Bid translocation during excitotoxic cell death using an antibody raised against the amino acids 1–58 of mouse Bid that is not able to detect tBid. Finally, inducible overexpression of FL-Bid or a Bid mutant that can not be cleaved by caspase-8 was sufficient to induce apoptosis in the hippocampal neuron cultures. Conclusion Our data suggest that translocation of FL-Bid is sufficient for the activation of mitochondrial cell death pathways in response to glutamate receptor overactivation.

  7. Contextual modulation of hippocampal activity during picture naming.

    Science.gov (United States)

    Llorens, A; Dubarry, A-S; Trébuchon, A; Chauvel, P; Alario, F-X; Liégeois-Chauvel, C

    2016-08-01

    Picture naming is a standard task used to probe language processes in healthy and impaired speakers. It recruits a broad neural network of language related areas, among which the hippocampus is rarely included. However, the hippocampus could play a role during picture naming, subtending, for example, implicit learning of the links between pictured objects and their names. To test this hypothesis, we recorded hippocampal activity during plain picture naming, without memorization requirement; we further assessed whether this activity was modulated by contextual factors such as repetition priming and semantic interference. Local field potentials recorded from intracerebral electrodes implanted in the healthy hippocampi of epileptic patients revealed a specific and reliable pattern of activity, markedly modulated by repetition priming and semantic context. These results indicate that the hippocampus is recruited during picture naming, presumably in relation to implicit learning, with contextual factors promoting differential hippocampal processes, possibly subtended by different sub-circuitries. PMID:27380274

  8. Organotypic hippocampal slice cultures for studies of brain damage, neuroprotection and neurorepair

    DEFF Research Database (Denmark)

    Noraberg, Jens; Poulsen, Frantz Rom; Blaabjerg, Morten;

    2005-01-01

    Slices of developing brain tissue can be grown for several weeks as so-called organotypic slice cultures. Here we summarize and review studies using hippocampal slice cultures to investigate mechanisms and treatment strategies for the neurodegenerative disorders like stroke (cerebral ischemia......), Alzheimer's disease (AD) and epilepsia. Studies of non-excitotoxic neurotoxic compounds and the experimental use of slice cultures in studies of HIV neurotoxicity, traumatic brain injury (TBI) and neurogenesis are included. For cerebral ischemia, experimental models with oxygen-glucose deprivation (OGD...... in vitro models using dispersed cell cultures, experimental in vivo models, and in some instances, clinical trials. New techniques including slice culturing of hippocampal tissue from transgenic mice as well as more mature brain tissue, and slice cultures coupled to microelectrode arrays (MEAs), on...

  9. P物质抑制培养大鼠海马大锥体细胞GABA-激活电流%Substance P depresses GABA-activated currents in cultured hippocampal pyramidal neurons of rats

    Institute of Scientific and Technical Information of China (English)

    熊顺华; 李之望; 樊友珍; 王明江; 魏劲波

    2001-01-01

    研究主要探讨P物质(SP)对GABA-激活电流的调制。实验在培养的新生大鼠海马大锥体细胞上进行, 应用全细胞膜片箝技术记录GABA激活的内向电流。在被检的大锥体细胞中, 有72%(66/92)的神经元对GABA和SP同时敏感。预加SP后, GABA激活电流明显地被抑制, 此抑制作用是呈剂量依赖性的, 在预加10-8、10-7、10-6、10-5 mol/L SP后, GABA的激活电流分别降低18%、24.8%、25.9%和28%。用SP的拮抗剂spantide能阻断此种抑制作用, 在电极中灌注H7 (PKC抑制剂)能取消此抑制作用。上述结果提示: SP对GABA激活电流的抑制作用是SP作用于SP受体, 通过胞内第二信使, 使GABAA受体通道复合体胞内磷酸化所致。%The purpose of the present study was to explore whether substance P (SP) modulates the response mediated by GABAA receptors. Experiments were carried out on cultured hippocampal pyramidal neurons of rats. GABA-activated inward currents were recorded using the whole-cell-patch-clamp techique. The majority of the neurons examined (66/92, 72%) were sensitive to both GABA and SP. When the neurons were treated with SP prior to application of GABA, the GABA-activated current (IGABA) was inhibited markedly, which was concentration-dependent and could be blocked by spantide, an NK1 receptor antagonist. With 10-8, 10-7, 10-6 and 10-5 mol/L SP, IGABA was inhibited by 18%, 24.8%, 25.9% and 28% respectively. Intracellular application of H7, a potent inhibitor of PKC, abolished inhibition of IGABA by SP, suggesting that the inhibition of IGABA by SP may be a result of intracellular phosphorylation of the GABAA receptor.

  10. A method for objectively quantifying propidium iodide exclusion in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Happ, Denise F; Tasker, Andrew

    2016-01-01

    BACKGROUND: Organotypic hippocampal slice cultures (OHSCs) are an attractive in vitro model to examine mechanisms of neuronal injury, because the normal hippocampal architecture, function and cellular diversity are mostly preserved. The effects of exposure to excitotoxins such as N......-methyl-d-aspartate (NMDA) on cell viability can be determined by propidium iodide (PI) staining. NEW METHOD: We describe a simple method to objectively quantify cell death in NMDA exposed slice cultures using PI that provides a standardized means of quantifying cell death in hippocampal subfields without the need to...... induce maximal cell death in each slice. The method employs separation of subfields using simple landmarks and densitometric quantification of PI intensity in 10 template-oriented counting fields. RESULTS: We show that exposure to increasing concentrations of NMDA results in a dose-dependent increase in...

  11. BDNF regulates the expression and distribution of vesicular glutamate transporters in cultured hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Carlos V Melo

    Full Text Available BDNF is a pro-survival protein involved in neuronal development and synaptic plasticity. BDNF strengthens excitatory synapses and contributes to LTP, presynaptically, through enhancement of glutamate release, and postsynaptically, via phosphorylation of neurotransmitter receptors, modulation of receptor traffic and activation of the translation machinery. We examined whether BDNF upregulated vesicular glutamate receptor (VGLUT 1 and 2 expression, which would partly account for the increased glutamate release in LTP. Cultured rat hippocampal neurons were incubated with 100 ng/ml BDNF, for different periods of time, and VGLUT gene and protein expression were assessed by real-time PCR and immunoblotting, respectively. At DIV7, exogenous application of BDNF rapidly increased VGLUT2 mRNA and protein levels, in a dose-dependent manner. VGLUT1 expression also increased but only transiently. However, at DIV14, BDNF stably increased VGLUT1 expression, whilst VGLUT2 levels remained low. Transcription inhibition with actinomycin-D or α-amanitine, and translation inhibition with emetine or anisomycin, fully blocked BDNF-induced VGLUT upregulation. Fluorescence microscopy imaging showed that BDNF stimulation upregulates the number, integrated density and intensity of VGLUT1 and VGLUT2 puncta in neurites of cultured hippocampal neurons (DIV7, indicating that the neurotrophin also affects the subcellular distribution of the transporter in developing neurons. Increased VGLUT1 somatic signals were also found 3 h after stimulation with BDNF, further suggesting an increased de novo transcription and translation. BDNF regulation of VGLUT expression was specifically mediated by BDNF, as no effect was found upon application of IGF-1 or bFGF, which activate other receptor tyrosine kinases. Moreover, inhibition of TrkB receptors with K252a and PLCγ signaling with U-73122 precluded BDNF-induced VGLUT upregulation. Hippocampal neurons express both isoforms during

  12. Recruitment of Perisomatic Inhibition during Spontaneous Hippocampal Activity In Vitro.

    Directory of Open Access Journals (Sweden)

    Anna Beyeler

    Full Text Available It was recently shown that perisomatic GABAergic inhibitory postsynaptic potentials (IPSPs originating from basket and chandelier cells can be recorded as population IPSPs from the hippocampal pyramidal layer using extracellular electrodes (eIPSPs. Taking advantage of this approach, we have investigated the recruitment of perisomatic inhibition during spontaneous hippocampal activity in vitro. Combining intracellular and extracellular recordings from pyramidal cells and interneurons, we confirm that inhibitory signals generated by basket cells can be recorded extracellularly, but our results suggest that, during spontaneous activity, eIPSPs are mostly confined to the CA3 rather than CA1 region. CA3 eIPSPs produced the powerful time-locked inhibition of multi-unit activity expected from perisomatic inhibition. Analysis of the temporal dynamics of spike discharges relative to eIPSPs suggests significant but moderate recruitment of excitatory and inhibitory neurons within the CA3 network on a 10 ms time scale, within which neurons recruit each other through recurrent collaterals and trigger powerful feedback inhibition. Such quantified parameters of neuronal interactions in the hippocampal network may serve as a basis for future characterisation of pathological conditions potentially affecting the interactions between excitation and inhibition in this circuit.

  13. Epoxyeicosatrienoic acids pretreatment improves amyloid β-induced mitochondrial dysfunction in cultured rat hippocampal astrocytes.

    Science.gov (United States)

    Sarkar, Pallabi; Zaja, Ivan; Bienengraeber, Martin; Rarick, Kevin R; Terashvili, Maia; Canfield, Scott; Falck, John R; Harder, David R

    2014-02-15

    Amyloid-β (Aβ) has long been implicated as a causative protein in Alzheimer's disease. Cellular Aβ accumulation is toxic and causes mitochondrial dysfunction, which precedes clinical symptoms of Alzheimer's disease pathology. In the present study, we explored the possible use of epoxyeicosatrienoic acids (EETs), epoxide metabolites of arachidonic acid, as therapeutic target against Aβ-induced mitochondrial impairment using cultured neonatal hippocampal astrocytes. Inhibition of endogenous EET production by a selective epoxygenase inhibitor, MS-PPOH, caused a greater reduction in mitochondrial membrane potential in the presence of Aβ (1, 10 μM) exposure versus absence of Aβ. MS-PPOH preincubation also aggravated Aβ-induced mitochondrial fragmentation. Preincubation of the cells with either 14,15- or 11,12-EET prevented this mitochondrial depolarization and fragmentation. EET pretreatment also further improved the reduction observed in mitochondrial oxygen consumption in the presence of Aβ. Preincubation of the cells with EETs significantly improved cellular respiration under basal condition and in the presence of the protonophore, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP). The uncoupling of ATP synthase from the electron transfer chain that occurred in Aβ-treated cells was also prevented by preincubation with EETs. Lastly, cellular reactive oxygen species production, a hallmark of Aβ toxicity, also showed significant reduction in the presence of EETs. We have previously shown that Aβ reduces EET synthesis in rat brain homogenates and cultured hippocampal astrocytes and neurons (Sarkar P, Narayanan J, Harder DR. Differential effect of amyloid beta on the cytochrome P450 epoxygenase activity in rat brain. Neuroscience 194: 241-249, 2011). We conclude that reduction of endogenous EETs may be one of the mechanisms through which Aβ inflicts toxicity and thus supplementing the cells with exogenous EETs improves mitochondrial dynamics and

  14. Apolipoprotein E isoform-dependent dendritic recovery of hippocampal neurons following activation of innate immunity

    Directory of Open Access Journals (Sweden)

    Maezawa Izumi

    2006-08-01

    Full Text Available Abstract Background Innate immune activation, including a role for cluster of differentiation 14/toll-like receptor 4 co-receptors (CD14/TLR-4 co-receptors, has been implicated in paracrine damage to neurons in several neurodegenerative diseases that also display stratification of risk or clinical outcome with the common alleles of the apolipoprotein E gene (APOE: APOE2, APOE3, and APOE4. Previously, we have shown that specific stimulation of CD14/TLR-4 with lipopolysaccharide (LPS leads to greatest innate immune response by primary microglial cultures from targeted replacement (TR APOE4 mice and greatest p38MAPK-dependent paracrine damage to neurons in mixed primary cultures and hippocampal slice cultures derived from TR APOE4 mice. In contrast, TR APOE2 astrocytes had the highest NF-kappaB activity and no neurotoxicity. Here we tested the hypothesis that direct activation of CD14/TLR-4 in vivo would yield different amounts of paracrine damage to hippocampal sector CA1 pyramidal neurons in TR APOE mice. Methods We measured in vivo changes in dendrite length in hippocampal CA1 neurons using Golgi staining and determined hippocampal apoE levels by Western blot. Neurite outgrowth of cultured primary neurons in response to astrocyte conditioned medium was assessed by measuring neuron length and branch number. Results Our results showed that TR APOE4 mice had slightly but significantly shorter dendrites at 6 weeks of age. Following exposure to intracerebroventricular LPS, there was comparable loss of dendrite length at 24 hr among the three TR APOE mice. Recovery of dendrite length over the next 48 hr was greater in TR APOE2 than TR APOE3 mice, while TR APOE4 mice had failure of dendrite regeneration. Cell culture experiments indicated that the enhanced neurotrophic effect of TR APOE2 was LDL related protein-dependent. Conclusion The data indicate that the environment within TR APOE2 mouse hippocampus was most supportive of dendrite regeneration

  15. Effects of GSM 1800 MHz on dendritic development of cultured hippo-campal neurons

    Institute of Scientific and Technical Information of China (English)

    Wei NING; Shu-jun XU; Huai CHIANG; Zheng-ping XU; Su-ya ZHOU; Wei YANG; Jian-hong LUO

    2007-01-01

    Aim: To evaluate the effects of global system for mobile communications (GSM)1800 MHz microwaves on dendritic filopodia, dendritic arborization, and spine maturation during development in cultured hippocampal neurons in rats. Methods: The cultured hippocampal neurons were exposed to GSM 1800 MHz microwaves with 2.4 and 0.8 W/kg, respectively, for 15 min each day from 6 days in vitro (DIV6) to DIV14. The subtle structures of dendrites were displayed by transfection with farnesylated enhanced green fluorescent protein (F-GFP) and GFP-actin on DIV5 into the hippocampal neurons. Results: There was a significant decrease in the density and mobility of dendritic filopodia at DIV8 and in the density of mature spines at DIV14 in the neurons exposed to GSM 1800 MHz microwaves with 2.4 W/kg. In addition, the average length of dendrites per neuron at DIV10 and DIV14 was decreased, while the dendritic arborization was unaltered in these neurons. However, there were no significant changes found in the neurons ex- posed to the GSM 1800 MHz microwaves with 0.8 W/kg. Conclusion: These data indicate that the chronic exposure to 2.4 W/kg GSM 1800 MHz micro- waves during the early developmental stage may affect dendritic development and the formation of excitatory synapses of hippocampal neurons in culture.

  16. Protective effect of naringenin on glutamate-induced neurotoxicity in cultured hippocampal cells

    Directory of Open Access Journals (Sweden)

    Xu Xiao-Hui

    2015-01-01

    Full Text Available Monosodium glutamate induces excitotoxicity in the central nervous system through hyperactivation of both ionotropic and metabotropic glutamate receptors, which leads to neuronal cell death. In this study, we investigated the neuroprotective effects of naringenin on excitotoxicity induced by glutamate in primary hippocampal neurons of neonatal mice. The expression levels of apoptosis-inducing proteins and as well as ischemic factors were observed by Western blot analysis. Immunocytochemistry and morphometric analysis of hippocampal cells with or without glutamate and naringenin treatment were performed. We observed that naringenin regulated Erk1/2 and Akt phosphorylation and reduced the demise of dendrites due to glutamate exposure in cultured hippocampal neurons. Furthermore, naringenin induced the brain-derived neurotrophic factor and other neuroprotective cytokines, and markedly improved the survival rates of the neurons 24 h following glutamate exposure. The observed results suggest that the naturally occurring bioflavonoid (naringenin exerts neuroprotective effects via highly specific molecular targets in neurons.

  17. Batroxobin Against Anoxic Damage of Rat Hippocampal Neurons in Culture: Morphological Changes and Hsp70 Expression

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Batroxobin,the thrombin-like enzyme,is used for therapeutic defibrination. We have found that batroxobin has good therapeutic effect in ischemic reperfusion rats and clinical practices in vivo. But we have not studied the neuroprotective effect of batroxobin on anoxic hippocampal neurons in vitro. The purpose of this study was to obtain further information on the mechanism of the batroxobin-induced neuroprotection and examine the neuroprotective effect on neurons exposed to anoxia. The effect of batroxobin on anoxic damages in cultured hippocampal neurons of neonatal rats was investigated by using morphological changes and heat shock protein 70Kd (Hsp70) immunoreactive expression as indicators. The results indicate that batroxobin, besides its defibrination, may have a direct neuroprotective effect on anoxic damage of hippocampal neurons.

  18. ZD7288, a selective hyperpolarization-activated cyclic nucleotide-gated channel blocker, inhibits hippocampal synaptic plasticity

    Institute of Scientific and Technical Information of China (English)

    Xiao-xue Zhang; Xiao-chun Min; Xu-lin Xu; Min Zheng; Lian-jun Guo

    2016-01-01

    The selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimeth-yl-6-(methylamino) pyrimidinium chloride (ZD7288) blocks the induction of long-term potentiation in the perforant path–CA3 region in rat hippocampusin vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path–CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hip-pocampal neurons using high performance liquid chromatography, and determined intracellular Ca2+ concentration ([Ca2+]i) using Fura-2. ZD7288 inhibited the induction and maintenance of long-term potentiation, and these effects were mirrored by the nonspeciifc HCN channel blocker cesium. ZD7288 also decreased glutamate release in hippocampal tissue and in cultured hippocampal neurons. Further-more, ZD7288 attenuated glutamate-induced rises in [Ca2+]i in a concentration-dependent manner and reversed 8-Br-cAMP-mediated facilitation of these glutamate-induced [Ca2+]i rises. Our results suggest that ZD7288 inhibits hippocampal synaptic plasticity both gluta-mate release and resultant [Ca2+]i increases in rat hippocampal neurons.

  19. Activity-dependent plasticity of mouse hippocampal assemblies in vitro

    Directory of Open Access Journals (Sweden)

    Martin eKeller

    2015-05-01

    Full Text Available Memory formation is associated with the generation of transiently stable neuronal assemblies. In hippocampal networks, such groups of functionally coupled neurons express highly ordered spatiotemporal activity patterns which are coordinated by local network oscillations. One of these patterns, sharp wave-ripple complexes (SPW-R, repetitively activates previously established groups of memory-encoding neurons, thereby supporting memory consolidation. This function implies that repetition of specific SPW-R induces plastic changes which render the underlying neuronal assemblies more stable. We modeled this repetitive activation in an in vitro model of SPW-R in mouse hippocampal slices. Weak electrical stimulation upstream of the CA3-CA1 networks reliably induced SPW-R of stereotypic waveform, thus representing re-activation of similar neuronal activity patterns. Frequent repetition of these patterns (100 times reduced the variance of both, evoked and spontaneous SPW-R waveforms, indicating stabilization of pre-existing assemblies. These effects were most pronounced in the CA1 subfield and depended on the timing of stimulation relative to spontaneous SPW-R. Additionally, plasticity of SPW-R was blocked by application of a NMDA receptor antagonist, suggesting a role for associative synaptic plasticity in this process. Thus, repetitive activation of specific patterns of SPW-R causes stabilization of memory-related networks.

  20. Time window characteristics of cultured rat hippocampal neurons subjected to ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    XU Zhong; XU Ru-xiang; LIU Bao-song; JIANG Xiao-dan; HUANG Tao; DING Lian-shu; YUAN Jun

    2005-01-01

    Objective: To explore cell death and apoptosis in rat hippocampal neurons at different time points after ischemia, hypoxia and reperfusion injury and to elucidate time window characteristics in ischemia neuronal injury.Methods: Hippocampal neurons were obtained from rat embryo and were cultured in vitro. The ischemia and reperfusion of cultured rat hippocampal neurons were simulated by oxygen-glucose deprivation (OGD) and recovery. OGD at different time points (0.25 h to 3.0 h) and then the same recovery (24 h) were prepared. Annexin V-PI staining and flow cytometry examined neuron death and apoptosis at different time after injury. Results: After OGD and recovery, both necrosis and apoptosis were observed. At different times after OGD, there were statistically significant differences in neuron necrosis rate (P0.05). At recovery, survival rate of hippocampal neurons further decreased while apoptosis rate increased. Furthermore, apoptosis rates of different time differed greatly (P<0.05). Apoptosis rate gradually increased with significant difference among those of different time points (P<0.05). However, 2 h after ischemia, apoptosis rate decreased markedly.Conclusions: Apoptosis is an important pathway of delayed neuron death. The therapeutic time window should be within 2 h after cerebral ischemia and hypoxia.

  1. Deoxyschisandrin modulates synchronized Ca2+ oscillations and spontaneous synaptic transmission of cultured hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Min FU; Zhao-hui SUN; Min ZONG; Xiang-ping HE; Huan-cong ZUO; Zuo-ping XIE

    2008-01-01

    Aim: Deoxyschisandrin is one of the most effective composites of Schisandra chinensis, a famous Chinese medicine widely used as an antistress, anti-aging, and neurological performance-improving herb. In this study, we examined its spe- cific mechanisms of action on cultured hippocampal neurons. Methods: Hippoc- ampal neurons, primarily cultured for 9-11 d in vitro, were used for this study. DS were dissolved in DMSO and applied to calcium imaging and whole-cell patch clamp. Results: The application of 3 mg/L DS decreased the frequency of sponta- neous and synchronous oscillations of intracellular Ca2+ to 72%±2% (mean±SEM), and the spontaneous inhibitory postsynaptic currents to 60%±3% (mean±SEM). The inhibitory concentraton 50% (IC50) for the effect of DS on calcium oscillations was 3.8 mg/L. DS also depressed the high voltage-gated Ca2+ channel and the voltage-gated Na+ channel currents at the same time point. It had no effect, however, on voltage-gated K+ and spontaneous excitatory postsynaptic currents. Conclusion: DS inhibited the spontaneous and synchronous oscillations of intra- cellular Ca2+ through the depression of influx of extracellular calcium and the initiation of action potential. By repressing the spontaneous neurotransmitter release, DS modulated the neuronal network activities.

  2. Achyranthes bidentata Blume extract promotes neuronal growth in cultured embryonic rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Xin Tang; Yiren Chen; Xiaosong Gu; Fei Ding

    2009-01-01

    We have prepared an aqueous extract of Achyranthes bidentata Blume,a commonly prescribed Chinese medicinal herb,and reported,in previous studies,that A.bidentata extract benefits nerve growth and prevents neuron apoptosis.In this study,we investigated the actions of ,4.bidentata extract on survival and growth of primarily cultured rat hippocampal neurons.The morphological observation revealed that neurite growth from hippocampal neurons was significantly enhanced by A.bidentata extract with similar effects to those induced by nerve growth factor (NGF),and the greatest neurite growth appeared on treatment with A.bidentata extract at 1 ttg/ml for 24 h.DNA microarray analysis indicated that there were 25 upregulated genes and 47 downregulated genes exhibiting significantly differential expression in hippocampal neurons treated with A.bidentata extract at 1 μg/ml for 6 h when compared to those in untreated hippocampal neurons.Real-time quantitative RT-PCR and Western blot analysis demonstrated that the expression of growth-associated protein-43 in hippocampal neurons was upregulated at both mRNA and protein levels after treatment with A.bidentata extract,and the optimal dosage of the extract was also 1 μg/ml.These data confirm that A.bidentata extract could promote in vitro hippocampal neuronal growth in a dose- and time-dependent manner.(C) 2009 National Natural Science Foundation of China and Chinese Academy of Sciences.Published by Elsevier Limited and Science in China Press.All rights reserved.

  3. Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Rai, R;

    1993-01-01

    In organotypic hippocampal slice cultures, kainate (KA) specifically induces cell loss in the CA3 region while N-methyl-D-aspartate induces cell loss in the CA1 region. The sensitivity of slice cultures to KA toxicity appears only after 2 weeks in vitro which parallels the appearance of mossy fib...... fibers. KA toxicity is potentiated by co-application with the GABA-A antagonist, picrotoxin. These data suggest that the excitotoxicity of KA in slice cultures is modulated by both excitatory and inhibitory synapses....

  4. A simplified micropatterning method for straight-line neurite extension of cultured hippocampal neurons.

    Science.gov (United States)

    Suzuki, Ikuro; Nakamura, Kosuke; Odawara, Aoi; Alhebshi, Amani; Gotoh, Masao

    2013-01-01

    We report a simplified micropatterning method for the straight-line extension of the neurites of cultured neurons. We prepared a poly-D-lysine (PDL)-patterned surface using a polydimethylsiloxane microfluidic stamp. Hippocampal neurons were cultured on the PDL-bound substrate with the stamp removed, allowing for conventional cell seeding and detailed optical observation without fluorescent label. Cultured neurons elongated neurites along straight lines at the single-cell level and displayed spontaneous firing as detected by time-lapse imaging and Ca(2+) imaging.

  5. Membrane potential dynamics of axons in cultured hippocampal neurons probed by second-harmonic-generation imaging

    Science.gov (United States)

    Nuriya, Mutsuo; Yasui, Masato

    2010-03-01

    The electrical properties of axons critically influence the nature of communication between neurons. However, due to their small size, direct measurement of membrane potential dynamics in intact and complex mammalian axons has been a challenge. Furthermore, quantitative optical measurements of axonal membrane potential dynamics have not been available. To characterize the basic principles of somatic voltage signal propagation in intact axonal arbors, second-harmonic-generation (SHG) imaging is applied to cultured mouse hippocampal neurons. When FM4-64 is applied extracellularly to dissociated neurons, whole axonal arbors are visualized by SHG imaging. Upon action potential generation by somatic current injection, nonattenuating action potentials are recorded in intact axonal arbors. Interestingly, however, both current- and voltage-clamp recordings suggest that nonregenerative subthreshold somatic voltage changes at the soma are poorly conveyed to these axonal sites. These results reveal the nature of membrane potential dynamics of cultured hippocampal neurons, and further show the possibility of SHG imaging in physiological investigations of axons.

  6. A Simplified Method for Ultra-Low Density, Long-Term Primary Hippocampal Neuron Culture.

    Science.gov (United States)

    Lu, Zhongming; Piechowicz, Mariel; Qiu, Shenfeng

    2016-01-01

    Culturing primary hippocampal neurons in vitro facilitates mechanistic interrogation of many aspects of neuronal development. Dissociated embryonic hippocampal neurons can often grow successfully on glass coverslips at high density under serum-free conditions, but low density cultures typically require a supply of trophic factors by co-culturing them with a glia feeder layer, preparation of which can be time-consuming and laborious. In addition, the presence of glia may confound interpretation of results and preclude studies on neuron-specific mechanisms. Here, a simplified method is presented for ultra-low density (~2,000 neurons/cm2), long-term (>3 months) primary hippocampal neuron culture that is under serum free conditions and without glia cell support. Low density neurons are grown on poly-D-lysine coated coverslips, and flipped on high density neurons grown in a 24-well plate. Instead of using paraffin dots to create a space between the two neuronal layers, the experimenters can simply etch the plastic bottom of the well, on which the high density neurons reside, to create a microspace conducive to low density neuron growth. The co-culture can be easily maintained for >3 months without significant loss of low density neurons, thus facilitating the morphological and physiological study of these neurons. To illustrate this successful culture condition, data are provided to show profuse synapse formation in low density cells after prolonged culture. This co-culture system also facilitates the survival of sparse individual neurons grown in islands of poly-D-lysine substrates and thus the formation of autaptic connections. PMID:27022758

  7. Effects of rhynchophylline on GluN1 and GluN2B expressions in primary cultured hippocampal neurons.

    Science.gov (United States)

    He, Yan; Zeng, Sheng-Ya; Zhou, Shi-Wen; Qian, Gui-Sheng; Peng, Kang; Mo, Zhi-Xian; Zhou, Ji-Yin

    2014-10-01

    N-methyl-d-aspartate (NMDA) receptor subunits GluN1 and GluN2B in hippocampal neurons play key roles in anxiety. Our previous studies show that rhynchophylline, an active component of the Uncaria species, down-regulates GluN2B expression in the hippocampal CA1 area of amphetamine-induced rat. The effects of rhynchophylline on expressions of GluN1 and GluN2B in primary hippocampal neurons in neonatal rats in vitro were investigated. Neonatal hippocampal neurons were cultured with neurobasal-A medium. After incubation for 6h or 48 h with rhynchophylline (non-competitive NMDAR antagonist) and MK-801 (non-competitive NMDAR antagonist with anxiolytic effect, as the control drug) from day 6, neuron toxicity, mRNA and protein expressions of GluN1 and GluN2B were analyzed. GluN1 is mainly distributed on neuronal axons and dendritic trunks, cytoplasm and cell membrane near axons and dendrites. GluN2B is mainly distributed on the membrane, dendrites, and axon membranes. GluN1 and GluN2B are codistributed on dendritic trunks and dendritic spines. After 48 h incubation, a lower concentration of rhynchophylline (lower than 400 μmol/L) and MK-801 (lower than 200 μmol/L) have no toxicity on neonatal hippocampal neurons. Rhynchophylline up-regulated GluN1 mRNA expression at 6h and mRNA and protein expressions at 48h, but down-regulated GluN2B mRNA and protein expressions at 48 h. However, GluN1 and GluN2B mRNA expressions were down-regulated at 6h, and mRNA and protein expressions were both up-regulated by MK-801 at 48h. These findings show that rhynchophylline reciprocally regulates GluN1 and GluN2B expressions in hippocampal neurons, indicating a potential anxiolytic property for rhynchophylline. PMID:25110195

  8. Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

    OpenAIRE

    Morte, Maria I.; Carreira, Bruno P.; Falcão, Maria J.; Ambrosio, António M.; Soares-da-Silva, Patrício; Araújo, Inês M.; Carvalho, Caetana M.

    2013-01-01

    In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic p...

  9. Nucleofection and Primary Culture of Embryonic Mouse Hippocampal and Cortical Neurons

    OpenAIRE

    Viesselmann, Christopher; Ballweg, Jason; Lumbard, Derek; Dent, Erik W.

    2011-01-01

    Hippocampal and cortical neurons have been used extensively to study central nervous system (CNS) neuronal polarization, axon/dendrite outgrowth, and synapse formation and function. An advantage of culturing these neurons is that they readily polarize, forming distinctive axons and dendrites, on a two dimensional substrate at very low densities. This property has made them extremely useful for determining many aspects of neuronal development. Furthermore, by providing glial conditioning for t...

  10. Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons

    OpenAIRE

    Ransom, Christopher B.; Tao, Wucheng; Wu, Yuanming; Spain, William J; Richerson, George B.

    2012-01-01

    Subacute and chronic changes in tonic GABAergic inhibition occur in human and experimental epilepsy. Less is known about how tonic inhibition is modulated over shorter time frames (seconds). We measured endogenous tonic GABA currents from cultured rat hippocampal neurons to evaluate how they are affected by 1) transient increases in extracellular GABA concentration ([GABA]), 2) transient postsynaptic depolarization, and 3) depolarization of presynaptic cells. Transient increases in [GABA] (1 ...

  11. Activity-dependent plasticity of hippocampal place maps.

    Science.gov (United States)

    Schoenenberger, Philipp; O'Neill, Joseph; Csicsvari, Jozsef

    2016-01-01

    Hippocampal neurons encode a cognitive map of space. These maps are thought to be updated during learning and in response to changes in the environment through activity-dependent synaptic plasticity. Here we examine how changes in activity influence spatial coding in rats using halorhodopsin-mediated, spatially selective optogenetic silencing. Halorhoposin stimulation leads to light-induced suppression in many place cells and interneurons; some place cells increase their firing through disinhibition, whereas some show no effect. We find that place fields of the unaffected subpopulation remain stable. On the other hand, place fields of suppressed place cells were unstable, showing remapping across sessions before and after optogenetic inhibition. Disinhibited place cells had stable maps but sustained an elevated firing rate. These findings suggest that place representation in the hippocampus is constantly governed by activity-dependent processes, and that disinhibition may provide a mechanism for rate remapping. PMID:27282121

  12. S-Nitrosoglutathione and glutathione act as NMDA receptor agonists in cultured hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Ting-yu CHIN; Sheau-huei CHUEH; Pao-luh TAO

    2006-01-01

    Aim: To characterize the effect of combined pre- and postnatal morphine exposure on Af-methyl-D-aspartate receptor (NMDA) receptor signaling in hippocampal neurons of the offspring of morphine-addicted female rats. Methods: Cultured hippocampal neurons and synaptosomes were prepared from neonatal and 2-week-old offspring, respectively, of control or morphine-addicted female rats. The increase in the cytosolic Ca2+ concentration ([Ca2+]i) of cultured cells was measured using Fura-2, and glutamate release from synaptosomes was measured enzymatically. Results: Both glutamate and NMDA caused a dose-dependent increase in the [Ca2+]i. The nitric oxide (NO) donor, S-nitrosoglutathione (GSNO), but not 3-morpholinosydnonimine, sodium nitroprusside, and S-nitroso-N-acetylpenicillamine, also induced a [Ca2+]i increase. GSNO and glutathione caused a dose-dependent increase in the [Ca2+]i with respective EC50 values of 56 and 414 μmol/L. Both effects were inhibited by Mg2+ or an NMDA receptor antagonist and were unaffected by the presence of a glutamate scavenger. The other glutathione derivatives, oxidized glutathione, S-methylglutathione, S-ethylglutathione, S-propylglutathione, and S-butylglutathione, the dipeptides, Glu-Cys and Cys-Gly, and the antioxidants, dithiothreitol and mercaptoethanol, failed to induce a [Ca2+]i increase. In addition, glutathione caused a dose-dependent increase in glutamate release from synaptosomes. The maximal responses and the EC50 values for the glutamate-, NMDA-, GSNO-, and glutathione-induced [Ca2+]i increases and the glutathione-induced glutamate release were indistinguishable in the neurons of the offspring from control and morphine-addicted female rats. Conclusion: GSNO and glutathione act as NMDA receptor agonists and, in contrast to hippocampal brain slice, combined pre- and postnatal morphine exposure does not modulate NMDA receptor signaling in the cultured hippocampal neurons.

  13. Colchicine induces apoptosis in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne W; Noer, Helle; Gramsbergen, Jan Bert;

    2003-01-01

    with the colchicine-induced apoptosis in 1-week-old cultures showed that colchicine-induced PI uptake and formation of apoptotic nuclei were temporarily prevented by coapplication of the protein synthesis inhibitor cycloheximide. Application of the pancaspase inhibitor z-VAD-fmk almost completely abolished...

  14. GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bonde, C; Kristensen, B W; Blaabjerg, M;

    2000-01-01

    The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN......-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN...

  15. Low-intensity daily walking activity is associated with hippocampal volume in older adults.

    Science.gov (United States)

    Varma, Vijay R; Chuang, Yi-Fang; Harris, Gregory C; Tan, Erwin J; Carlson, Michelle C

    2015-05-01

    Hippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimer's disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficulty initiating and maintaining exercise programs. A modestly more active lifestyle may nonetheless be beneficial. This study explored whether greater objectively measured daily walking activity was associated with larger hippocampal volume. We additionally explored whether greater low-intensity walking activity, which may be related to leisure-time physical, functional, and social activities, was associated with larger hippocampal volume independent of exercise and higher-intensity walking activity. Segmentation of hippocampal volumes was performed using Functional Magnetic Resonance Imaging of the Brain's Software Library (FSL), and daily walking activity was assessed using a step activity monitor on 92, nondemented, older adult participants. After controlling for age, education, body mass index, cardiovascular disease risk factors, and the Mini Mental State Exam, we found that a greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampal volume among older women, but not among men. These relationships were specific to hippocampal volume, compared with the thalamus, used as a control brain region, and remained significant for low-intensity walking activity, independent of moderate- to vigorous-intensity activity and self-reported exercise. This is the first study, to our knowledge, to explore the relationship between objectively measured daily walking activity and hippocampal volume in an older adult population. Findings

  16. A study of epileptogenic network structures in rat hippocampal cultures using first spike latencies during synchronization events

    International Nuclear Information System (INIS)

    Study of hypersynchronous activity is of prime importance for combating epilepsy. Studies on network structure typically reconstruct the network by measuring various aspects of the interaction between neurons and subsequently measure the properties of the reconstructed network. In sub-sampled networks such methods lead to significant errors in reconstruction. Using rat hippocampal neurons cultured on a multi-electrode array dish and a glutamate injury model of epilepsy in vitro, we studied synchronous activity in neuronal networks. Using the first spike latencies in various neurons during a network burst, we extract various recurring spatio-temporal onset patterns in the networks. Comparing the patterns seen in control and injured networks, we observe that injured networks express a wide diversity in their foci (origin) and activation pattern, while control networks show limited diversity. Furthermore, we note that onset patterns in glutamate injured networks show a positive correlation between synchronization delay and physical distance between neurons, while control networks do not. (paper)

  17. Concentration-dependent effects of fullerenol on cultured hippocampal neuron viability

    Directory of Open Access Journals (Sweden)

    Zha YY

    2012-06-01

    Full Text Available Ying-ying Zha,1 Bo Yang,1 Ming-liang Tang,2 Qiu-chen Guo,1 Ju-tao Chen,1 Long-ping Wen,3 Ming Wang11CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 2Suzhou Institute of NanoTech and NanoBionics, Chinese Academy of Sciences, Suzhou, 3Laboratory of Nano-biology, School of Life Sciences, University of Science and Technology of China, Hefei, People's Republic of ChinaBackground: Recent studies have shown that the biological actions and toxicity of the water-soluble compound, polyhydroxyfullerene (fullerenol, are related to the concentrations present at a particular site of action. This study investigated the effects of different concentrations of fullerenol on cultured rat hippocampal neurons.Methods and results: Fullerenol at low concentrations significantly enhanced hippocampal neuron viability as tested by MTT assay and Hoechst 33342/propidium iodide double stain detection. At high concentrations, fullerenol induced apoptosis confirmed by Comet assay and assessment of caspase proteins.Conclusion: These findings suggest that fullerenol promotes cell death and protects against cell damage, depending on the concentration present. The concentration-dependent effects of fullerenol were mainly due to its influence on the reduction-oxidation pathway.Keywords: fullerenol, nanomaterial, neurotoxicity, neuroprotection, hippocampal neuron

  18. Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones.

    OpenAIRE

    Orser, B. A.; Bertlik, M.; Wang, L. Y.; MacDonald, J. F.

    1995-01-01

    1. The effects of propofol (2,6 di-isopropylphenol) on responses to the selective glutamate receptor agonists, N-methyl-D-aspartate (NMDA) and kainate, were investigated in cultured hippocampal neurones of the mouse. Whole cell and single channel currents were recorded by patch-clamp techniques. Drugs were applied with a multi-barrel perfusion system. 2. Propofol produced a reversible, dose-dependent inhibition of whole cell currents activated by NMDA. The concentration of propofol which indu...

  19. Hippocampal inactivation with TTX impairs long-term spatial memory retrieval and modifies brain metabolic activity.

    Science.gov (United States)

    Conejo, Nélida María; Cimadevilla, José Manuel; González-Pardo, Héctor; Méndez-Couz, Marta; Arias, Jorge Luis

    2013-01-01

    Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions. PMID:23724089

  20. Glutamate induces the rapid formation of spine head protrusions in hippocampal slice cultures

    OpenAIRE

    David A Richards; Mateos, José Maria; Hugel, Sylvain; De Paola, Vincenzo; CARONI, Pico; Gähwiler, Beat H.; McKinney, R. Anne

    2005-01-01

    Synaptic plasticity at neuronal connections has been well characterized functionally by using electrophysiological approaches, but the structural basis for this phenomenon remains controversial. We have studied the dynamic interactions between presynaptic and postsynaptic structures labeled with FM 4-64 and a membrane-targeted GFP, respectively, in hippocampal slices. Under conditions of reduced neuronal activity (1 μM tetrodotoxin), we observed extension of glutamate receptor-dependent proce...

  1. Long-term live imaging of neuronal circuits in organotypic hippocampal slice cultures.

    Science.gov (United States)

    Gogolla, Nadine; Galimberti, Ivan; DePaola, Vincenzo; Caroni, Pico

    2006-01-01

    This protocol details a method for imaging organotypic slice cultures from the mouse hippocampus. The cultures are based on the interface method, which does not require special equipment, is easy to execute, and yields slice cultures that can be imaged repeatedly after they are isolated on postnatal day 6-9 and for up to 6 months in vitro. The preserved tissue architecture facilitates the analysis of defined hippocampal synapses, cells and entire projections. Time-lapse imaging is based on transgenes expressed in the mice, or on constructs introduced through transfection or viral vectors; it can reveal processes that develop over time periods ranging from seconds to months. Imaging can be repeated at least eight times without detectable morphological damage to neurons. Subsequent to imaging, the slices can be processed for immunocytochemistry or electron microscopy, to collect further information about the structures that have been imaged. This protocol can be completed in 35 min.

  2. Preparation of organotypic hippocampal slice cultures for long-term live imaging.

    Science.gov (United States)

    Gogolla, Nadine; Galimberti, Ivan; DePaola, Vincenzo; Caroni, Pico

    2006-01-01

    This protocol details a method to establish organotypic slice cultures from mouse hippocampus, which can be maintained for several months. The cultures are based on the interface method, which does not require special equipment, is easy to execute and yields slice cultures that can be imaged repeatedly--from when they are isolated at postnatal day 6-9, and up to 6 months in vitro. The preserved tissue architecture facilitates the analysis of defined hippocampal synapses, cells and entire projections. Monitoring of defined cellular and molecular components in the slices can be achieved by preparing slices from transgenic mice or by introducing transgenes through transfection or viral vectors. This protocol can be completed in 3 h.

  3. DIDS prevents ischemic membrane degradation in cultured hippocampal neurons by inhibiting matrix metalloproteinase release.

    Directory of Open Access Journals (Sweden)

    Matthew E Pamenter

    Full Text Available During stroke, cells in the infarct core exhibit rapid failure of their permeability barriers, which releases ions and inflammatory molecules that are deleterious to nearby tissue (the penumbra. Plasma membrane degradation is key to penumbral spread and is mediated by matrix metalloproteinases (MMPs, which are released via vesicular exocytosis into the extracellular fluid in response to stress. DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid preserves membrane integrity in neurons challenged with an in vitro ischemic penumbral mimic (ischemic solution: IS and we asked whether this action was mediated via inhibition of MMP activity. In cultured murine hippocampal neurons challenged with IS, intracellular proMMP-2 and -9 expression increased 4-10 fold and extracellular latent and active MMP isoform expression increased 2-22 fold. MMP-mediated extracellular gelatinolytic activity increased ∼20-50 fold, causing detachment of 32.1±4.5% of cells from the matrix and extensive plasma membrane degradation (>60% of cells took up vital dyes and >60% of plasma membranes were fragmented or blebbed. DIDS abolished cellular detachment and membrane degradation in neurons and the pathology-induced extracellular expression of latent and active MMPs. DIDS similarly inhibited extracellular MMP expression and cellular detachment induced by the pro-apoptotic agent staurosporine or the general proteinase agonist 4-aminophenylmercuric acetate (APMA. Conversely, DIDS-treatment did not impair stress-induced intracellular proMMP production, nor the intracellular cleavage of proMMP-2 to the active form, suggesting DIDS interferes with the vesicular extrusion of MMPs rather than directly inhibiting proteinase expression or activation. In support of this hypothesis, an antagonist of the V-type vesicular ATPase also inhibited extracellular MMP expression to a similar degree as DIDS. In addition, in a proteinase-independent model of vesicular exocytosis, DIDS

  4. Abelson tyrosine kinase links PDGFbeta receptor activation to cytoskeletal regulation of NMDA receptors in CA1 hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Beazely Michael A

    2008-12-01

    Full Text Available Abstract Background We have previously demonstrated that PDGF receptor activation indirectly inhibits N-methyl-D-aspartate (NMDA currents by modifying the cytoskeleton. PDGF receptor ligand is also neuroprotective in hippocampal slices and cultured neurons. PDGF receptors are tyrosine kinases that control a variety of signal transduction pathways including those mediated by PLCγ. In fibroblasts Src and another non-receptor tyrosine kinase, Abelson kinase (Abl, control PDGF receptor regulation of cytoskeletal dynamics. The mechanism whereby PDGF receptor regulates cytoskeletal dynamics in central neurons remains poorly understood. Results Intracellular applications of active Abl, but not heat-inactivated Abl, decreased NMDA-evoked currents in isolated hippocampal neurons. This mimics the effects of PDGF receptor activation in these neurons. The Abl kinase inhibitor, STI571, blocked the inhibition of NMDA currents by Abl. We demonstrate that PDGF receptors can activate Abl kinase in hippocampal neurons via mechanisms similar to those observed previously in fibroblasts. Furthermore, PDGFβ receptor activation alters the subcellular localization of Abl. Abl kinase is linked to actin cytoskeletal dynamics in many systems. We show that the inhibition of NMDA receptor currents by Abl kinase is blocked by the inclusion of the Rho kinase inhibitor, Y-27632, and that activation of Abl correlates with an increase in ROCK tyrosine phosphorylation. Conclusion This study demonstrates that PDGFβ receptors act via an interaction with Abl kinase and Rho kinase to regulated cytoskeletal regulation of NMDA receptor channels in CA1 pyramidal neurons.

  5. Corticosterone activates Erk1/2 mitogen-activated protein kinase in primary hippocampal cells through rapid nongenomic mechanism

    Institute of Scientific and Technical Information of China (English)

    QI Aiqun; QIU Jian; XIAO Lin; CHEN Yizhang

    2005-01-01

    Nongenomic effects of glucocorticoids (GC) in various cell types have been well documented, but it still remains unknown whether the mechanism also works in hippocampus which is a crucial target of glucocorticoids in neural system during physiological and/or pathophysiological processes. We present here that corticosterone (B) could rapidly activate Erk1/2 mitogen-activated protein kinase (MAPK) in primarily cultured hippocampal cells within minutes, with a bell-shaped time dependent curve which peaked at 15min and then went down to normal level in 30 min. This activation was blocked by protein kinase C (PKC) inhibitor (Go6976), G protein inhibitor (GDPβs), and MEK(MAPK/extracellular signal-regulated kinase kinase) inhibitor(PD98059), but not by protein kinase A (PKA) inbibitor (H89), tyrosine kinase inhibitor (genistein), and glucocorticoid receptor ( GR ) antagonist (RU38486). Thus, the rapid activation of Erk1/2 MAPK in primary hippocampal cells induced by B was likely mediated by a G protein coupled receptor (GPCR) pathway with involvement of PKC, which belonged to the nongenomic rather than genomic mechanism of GC' s effects.

  6. Low-intensity daily walking activity is associated with hippocampal volume in older adults

    OpenAIRE

    Varma, Vijay R.; Chuang, Yi-Fang; Harris, Gregory C.; Tan, Erwin J.; Carlson, Michelle C.

    2014-01-01

    Hippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimer's disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficul...

  7. Excitatory Effects of Parvalbumin-Expressing Interneurons Maintain Hippocampal Epileptiform Activity via Synchronous Afterdischarges

    OpenAIRE

    Ellender, Tommas J.; Raimondo, Joseph V.; Irkle, Agnese; Karri P Lamsa; Akerman, Colin J.

    2014-01-01

    Epileptic seizures are characterized by periods of hypersynchronous, hyperexcitability within brain networks. Most seizures involve two stages: an initial tonic phase, followed by a longer clonic phase that is characterized by rhythmic bouts of synchronized network activity called afterdischarges (ADs). Here we investigate the cellular and network mechanisms underlying hippocampal ADs in an effort to understand how they maintain seizure activity. Using in vitro hippocampal slice models from r...

  8. Mechanism underlying blockade of voltage-gated calcium channels by agmatine in cultured rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Jian-quan ZHENG; Xie-chuan WENG; Xiao-dan GAI; Jin LI; Wen-bin XIAO

    2004-01-01

    AIM: To investigate whether agmatine could selectively block a given type of the voltage-gated calcium channels (VGCC) and whether related receptors are involved in the blocking effect of agmatine on VGCC. METHODS: The whole-cell patch recording technique was performed to record VGCC currents in the cultured neonatal rat hippocampal neurons. RESULTS: Verapamil (100 μmol/L), a selective blocker of L-type calcium channel, significantly inhibited VGCC current by 80 %± 7 %. Agmatine (100 μmol/L) could further depress the remained currents by 25 %±6 %. The α2-adrenoceptor antagonist yohimbine (10 μmol/L) and the I2 imidazoline receptor antagonist idazoxon (10 and 40 μmol/L) had no significant effect on VGCC currents when used respectively. When the mixture of yohimbine and agmatine was applied, VGCC currents were still depressed remarkably. However, the blocking effect of agmatine was decreased by 29 %± 8 % in the presence of idazoxon (10 μmol/L). The effect of idazoxon did not increase at a higher concentration (40 μmol/L). CONCLUSION: Agmatine could block the L- and other types of VGCC currents in the cultured rat hippocampal neurons. Blocking effect of agmatine on VGCC was partially related to I2 imidazoline receptor and had no relationship with α2-adrenoceptors.

  9. Effect of New O-Superfamily Conotoxin on Voltage-Activated Currents of Hippocampal Neurons

    Institute of Scientific and Technical Information of China (English)

    李湛; 何湘平; 戴秋云; 黄培堂; 谢佐平

    2004-01-01

    The effects of a new O-superfamily conotoxin, SO3, on sodium current (/Na), transient A-type potassium currents (/A), and delayed rectified potassium currents (/K), were examined in cultured rat hippocampal neurons using the whole-cell patch clamp technique. Addition of SO3 caused a concentration-dependent,rapidly developing, and reversible inhibition of voltage-activated currents. The IC50 values for the blockage of /Na, /A, and /K were calculated as 0.49, 33.9, and 7.6 μmol/L, respectively. The determined Hill coefficients were 1.7, 0.6, and 1.2, respectively. These results indicate that SO3 can selectively inhibit neuronal sodium and potassium currents.

  10. Effect of polybrominated diphenyl ether on development of cultured hippocampal neuron

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Polybrominated diphenyl ether (PBDE) is a persistently environmental pollutant ubiquitously found in wildlife and humans. Although concern on PBDE’s toxic effects is steadily increasing, its action on the central nervous system (CNS) remains largely unknown. To address this issue, the present study ex- amined the development inhibition of PBDE in neurons. The primary cultured hippocampal neurons of rat were exposed to the commercial decabromodiphenyl ether (deca-BDE), and the neurite length, bi- furcation, and synapse formation and maturation were evaluated, based on the confocal microscope imaging. The results showed that the development inhibition in neurons occurred at 15 μmol/L, indi- cating that PBDE is a potent neurotoxicant and it might obviously inhibit the development of cultured neurons.

  11. Effect of polybrominated diphenyl ether on development of cultured hippocampal neuron

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Polybrominated diphenyl ether (PBDE) is a persistently environmental pollutant ubiquitously found in wildlife and humans. Although concern on PBDE's toxic effects is steadily increasing, its action on the central nervous system (CNS) remains largely unknown. To address this issue, the present study examined the development inhibition of PBDE in neurons. The primary cultured hippocampal neurons of rat were exposed to the commercial decabromodiphenyl ether (deca-BDE), and the neurite length, bifurcation, and synapse formation and maturation were evaluated, based on the confocal microscope imaging. The results showed that the development inhibition in neurons occurred at 15 μmol/L, indicating that PBDE is a potent neurotoxicant and it might obviously inhibit the development of cultured neurons.

  12. Topiramate protects against glutamate excitotoxicity via activating BDNF/TrkB-dependent ERK pathway in rodent hippocampal neurons.

    Science.gov (United States)

    Mao, Xiao-Yuan; Cao, Yong-Gang; Ji, Zhong; Zhou, Hong-Hao; Liu, Zhao-Qian; Sun, Hong-Li

    2015-07-01

    Topiramate (TPM) was previously found to have neuroprotection against neuronal injury in epileptic and ischemic models. However, whether TPM protects against glutamate-induced excitotoxicity in hippocampal neurons is elusive. Our present work aimed to evaluate the protective effect of TPM against glutamate toxicity in hippocampal neurons and further figure out the potential molecular mechanisms. The in vitro glutamate excitotoxic model was prepared with 125μM glutamate for 20min. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) analysis and Hoechst 33342 staining were conducted to detect neuronal survival. The protein expressions of brain-derived neurotrophic factor (BDNF), TrkB, mitogen-activated protein kinase (MAPK) cascade (including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK), cyclic AMP response element binding protein (CREB), Bcl-2, Bax and β-actin were detected via Western blot assay. Our results demonstrated that TPM protected hippocampal neurons from glutamate toxicity. Meanwhile, the pretreatment of TPM for 10min significantly prevented the down-regulation of BDNF and the phosphorylation of TrkB. Furthermore, the elevation of phosphorylated EKR expression was significantly inhibited after blockade of TrkB by TrkB IgG, while no alterations of phosphorylated JNK and p38 MAPK were found in the cultured hippocampal neurons. Besides, it was also found that the enhanced phosphorylation of CREB was evidently reversed under excitotoxic conditions after treating with U0126 (the selective inhibitor of ERK). The protein level of Bcl-2 was also observed to be remarkably increased after TPM treatment. In conclusion, these findings implicate that TPM exerts neuroprotective effects against glutamate excitotoxicity in hippocampal neurons and its protection may be modulated through BDNF/TrkB-dependent ERK pathway.

  13. Carbachol-induced rhythmic slow activity (theta) in cat hippocampal formation slices.

    Science.gov (United States)

    Konopacki, J; Gołebiewski, H; Eckersdorf, B

    1992-04-24

    Application of the cholinergic agonist, carbachol, produced theta-like rhythmical waveforms, recorded in the stratum moleculare of the dentate gyrus in the cat hippocampal formation slices. This effect of carbachol was antagonized by atropine but not D-tubocurarine. These results provide first direct evidence that the hippocampal formation neuronal network in the cat is capable of producing synchronized slow wave activity when isolated from pulsed rhythmic inputs of the medial septum. PMID:1511270

  14. Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

    Directory of Open Access Journals (Sweden)

    Williams Sylvain

    2006-03-01

    Full Text Available Abstract Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+-butaclamol and L-741,742. These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (--raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (--raclopride (10-6 M was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M. Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.

  15. The effects of temperature on vesicular supply and release in autaptic cultures of rat and mouse hippocampal neurons

    NARCIS (Netherlands)

    Pyott, Sonja J; Rosenmund, Christian

    2002-01-01

    Membrane fusion plays a central role in the synaptic vesicle cycle. While many of the pre- and postfusion events have been investigated at room temperature, few researchers have investigated these processes at more physiologically relevant temperatures. We have used autaptic cultures of hippocampal

  16. Sleep restriction by forced activity reduces hippocampal cell proliferation

    NARCIS (Netherlands)

    Roman, Viktor; Van der Borght, K; Leemburg, SA; Van der Zee, EA; Meerlo, P

    2005-01-01

    Mounting evidence suggests that sleep loss negatively affects learning and memory processes through disruption of hippocampal function. In the present study, we examined whether sleep loss alters the generation, differentiation, and survival of new cells in the dentate gyrus. Rats were sleep restric

  17. Apoptosis after irradiation of the rat cortical and hippocampal cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Coffigny, H.; Lane, M.C. [CEA Fontenay-aux-Roses, Direction des Sciences du Vivant-DRR-LRO, 92 (France)

    1997-03-01

    During the development of the central nervous system many neurons are generated but over 50% die by natural apoptosis; this phenomenon occurred in neurons without or with wrong connections with their target cells. Children exposed in utero to Hiroshima or Nagasaki bombing presented microcephaly due to cell deaths and mental retardation. In animals, the number of apoptotic cells in the developing central nervous system increased as a function of the dose received. In vitro, we have shown that 1 Gy irradiation induced 50 % decrease of cortical and hippocampal cell survival. Nervous cells when seeded in a plate were round without processes. Neuritis outgrowth increased with culture time and physical contacts were established between cells. Our purpose is to test the importance of these contacts in the radio-induced apoptosis. (authors)

  18. Effects of cordycepin on the microglia-overactivation-induced impairments of growth and development of hippocampal cultured neurons.

    Directory of Open Access Journals (Sweden)

    Jie Peng

    Full Text Available Microglial cells are normally activated in response to brain injury or immunological stimuli to protect central nervous system (CNS. However, over-activation of microglia conversely amplifies the inflammatory effects and mediates cellular degeneration, leading to the death of neurons. Recently, cordycepin, an active component found in Cordyceps militarisa known as a rare Chinese caterpillar fungus, has been reported as an effective drug for treating inflammatory diseases and cancer via unclear mechanisms. In this study, we attempted to identify the anti-inflammatory role of cordycepin and its protective effects on the impairments of neural growth and development induced by microglial over-activation. The results indicate that cordycepin could attenuate the lipopolysaccharide (LPS-induced microglial activation, evidenced by the dramatically reduced release of TNF-α and IL-1β, as well as the down-regulation of mRNA levels of iNOS and COX-2 after cordycepin treatment. Besides, cordycepin reversed the LPS-induced activation of NF-κB pathway, resulting in anti-inflammatory effects. Furthermore, by employing the conditioned medium (CM, we found cordycepin was able to recover the impairments of neural growth and development in the primary hippocampal neurons cultured in LPS-CM, including cell viability, growth cone extension, neurite sprouting and outgrowth as well as spinogenesis. This study expands our knowledge of the anti-inflammatory function of cordycepin and paves the way for the biomedical applications of cordycepin in the therapies of neural injuries.

  19. Hippocampal activation during face-name associative memory encoding: blocked versus permuted design

    Energy Technology Data Exchange (ETDEWEB)

    De Vogelaere, Frederick; Vingerhoets, Guy [Ghent University, Laboratory for Neuropsychology, Department of Neurology, Ghent (Belgium); Santens, Patrick; Boon, Paul [Ghent University Hospital, Department of Neurology, Ghent (Belgium); Achten, Erik [Ghent University Hospital, Department of Radiology, Ghent (Belgium)

    2010-01-15

    The contribution of the hippocampal subregions to episodic memory through the formation of new associations between previously unrelated items such as faces and names is established but remains under discussion. Block design studies in this area of research generally tend to show posterior hippocampal activation during encoding of novel associational material while event-related studies emphasize anterior hippocampal involvement. We used functional magnetic resonance imaging to assess the involvement of anterior and posterior hippocampus in the encoding of novel associational material compared to the viewing of previously seen associational material. We used two different experimental designs, a block design and a permuted block design, and applied it to the same associative memory task to perform valid statistical comparisons. Our results indicate that the permuted design was able to capture more anterior hippocampal activation compared to the block design, which emphasized more posterior hippocampal involvement. These differences were further investigated and attributed to a combination of the polymodal stimuli we used and the experimental design. Activation patterns during encoding in both designs occurred along the entire longitudinal axis of the hippocampus, but with different centers of gravity. The maximal activated voxel in the block design was situated in the posterior half of the hippocampus while in the permuted design this was located in the anterior half. (orig.)

  20. Developmental Changes in Hippocampal CA1 Single Neuron Firing and Theta Activity during Associative Learning

    Science.gov (United States)

    Kim, Jangjin; Goldsberry, Mary E.; Harmon, Thomas C.; Freeman, John H.

    2016-01-01

    Hippocampal development is thought to play a crucial role in the emergence of many forms of learning and memory, but ontogenetic changes in hippocampal activity during learning have not been examined thoroughly. We examined the ontogeny of hippocampal function by recording theta and single neuron activity from the dorsal hippocampal CA1 area while rat pups were trained in associative learning. Three different age groups [postnatal days (P)17-19, P21-23, and P24-26] were trained over six sessions using a tone conditioned stimulus (CS) and a periorbital stimulation unconditioned stimulus (US). Learning increased as a function of age, with the P21-23 and P24-26 groups learning faster than the P17-19 group. Age- and learning-related changes in both theta and single neuron activity were observed. CA1 pyramidal cells in the older age groups showed greater task-related activity than the P17-19 group during CS-US paired sessions. The proportion of trials with a significant theta (4–10 Hz) power change, the theta/delta ratio, and theta peak frequency also increased in an age-dependent manner. Finally, spike/theta phase-locking during the CS showed an age-related increase. The findings indicate substantial developmental changes in dorsal hippocampal function that may play a role in the ontogeny of learning and memory. PMID:27764172

  1. Calcium-sensitive regulation of monoamine oxidase-A contributes to the production of peroxyradicals in hippocampal cultures: implications for Alzheimer disease-related pathology

    Directory of Open Access Journals (Sweden)

    Li XinMin

    2007-09-01

    Full Text Available Abstract Background Calcium (Ca2+ has recently been shown to selectively increase the activity of monoamine oxidase-A (MAO-A, a mitochondria-bound enzyme that generates peroxyradicals as a natural by-product of the deamination of neurotransmitters such as serotonin. It has also been suggested that increased intracellular free Ca2+ levels as well as MAO-A may be contributing to the oxidative stress associated with Alzheimer disease (AD. Results Incubation with Ca2+ selectively increases MAO-A enzymatic activity in protein extracts from mouse hippocampal HT-22 cell cultures. Treatment of HT-22 cultures with the Ca2+ ionophore A23187 also increases MAO-A activity, whereas overexpression of calbindin-D28K (CB-28K, a Ca2+-binding protein in brain that is greatly reduced in AD, decreases MAO-A activity. The effects of A23187 and CB-28K are both independent of any change in MAO-A protein or gene expression. The toxicity (via production of peroxyradicals and/or chromatin condensation associated with either A23187 or the AD-related β-amyloid peptide, which also increases free intracellular Ca2+, is attenuated by MAO-A inhibition in HT-22 cells as well as in primary hippocampal cultures. Conclusion These data suggest that increases in intracellular Ca2+ availability could contribute to a MAO-A-mediated mechanism with a role in AD-related oxidative stress.

  2. Hippocampal activity mediates the relationship between circadian activity rhythms and memory in older adults.

    Science.gov (United States)

    Sherman, Stephanie M; Mumford, Jeanette A; Schnyer, David M

    2015-08-01

    Older adults experience parallel changes in sleep, circadian rhythms, and episodic memory. These processes appear to be linked such that disruptions in sleep contribute to deficits in memory. Although more variability in circadian patterns is a common feature of aging and predicts pathology, little is known about how alterations in circadian activity rhythms within older adults influence new episodic learning. Following 10 days of recording sleep-wake patterns using actigraphy, healthy older adults underwent fMRI while performing an associative memory task. The results revealed better associative memory was related to more consistent circadian activity rhythms, independent of total sleep time, sleep efficiency, and level of physical activity. Moreover, hippocampal activity during successful memory retrieval events was positively correlated with associative memory accuracy and circadian activity rhythm (CAR) consistency. We demonstrated that the link between consistent rhythms and associative memory performance was mediated by hippocampal activity. These findings provide novel insight into how the circadian rhythm of sleep-wake cycles are associated with memory in older adults and encourage further examination of circadian activity rhythms as a biomarker of cognitive functioning. PMID:26205911

  3. Hippocampal CA2 activity patterns change over time to a larger extent than between spatial contexts.

    Science.gov (United States)

    Mankin, Emily A; Diehl, Geoffrey W; Sparks, Fraser T; Leutgeb, Stefan; Leutgeb, Jill K

    2015-01-01

    The hippocampal CA2 subregion has a different anatomical connectivity pattern within the entorhino-hippocampal circuit than either the CA1 or CA3 subregion. Yet major differences in the neuronal activity patterns of CA2 compared with the other CA subregions have not been reported. We show that standard spatial and temporal firing patterns of individual hippocampal principal neurons in behaving rats, such as place fields, theta modulation, and phase precession, are also present in CA2, but that the CA2 subregion differs substantially from the other CA subregions in its population coding. CA2 ensembles do not show a persistent code for space or for differences in context. Rather, CA2 activity patterns become progressively dissimilar over time periods of hours to days. The weak coding for a particular context is consistent with recent behavioral evidence that CA2 circuits preferentially support social, emotional, and temporal rather than spatial aspects of memory. PMID:25569350

  4. NRSF causes cAMP-sensitive suppression of sodium current in cultured hippocampal neurons

    Science.gov (United States)

    Nadeau, H.; Lester, H. A.

    2002-01-01

    The neuron restrictive silencer factor (NRSF/REST) has been shown to bind to the promoters of many neuron-specific genes and is able to suppress transcription of Na(+) channels in PC12 cells, although its functional effect in terminally differentiated neurons is unknown. We constructed lentiviral vectors to express NRSF as a bicistronic message with green fluorescent protein (GFP) and followed infected hippocampal neurons in culture over a period of 1-2 wk. NRSF-expressing neurons showed a time-dependent suppression of Na(+) channel function as measured by whole cell electrophysiology. Suppression was reversed or prevented by the addition of membrane-permeable cAMP analogues and enhanced by cAMP antagonists but not affected by increasing protein expression with a viral enhancer. Secondary effects, including altered sensitivity to glutamate and GABA and reduced outward K(+) currents, were duplicated by culturing GFP-infected control neurons in TTX. The striking similarity of the phenotypes makes NRSF potentially useful as a genetic "silencer" and also suggests avenues of further exploration that may elucidate the transcription factor's in vivo role in neuronal plasticity.

  5. Nanoparticle targeting to neurons in a rat hippocampal slice culture model

    Directory of Open Access Journals (Sweden)

    Richard P Kraig

    2012-10-01

    Full Text Available We have previously shown that CdSe/ZnS core/shell luminescent semiconductor nanocrystals or QDs (quantum dots coated with PEG [poly(ethylene glycol]-appended DHLA (dihydrolipoic acid can bind AcWG(PalVKIKKP9GGH6 (Palm1 through the histidine residues. The coating on the QD provides colloidal stability and this peptide complex uniquely allows the QDs to be taken up by cultured cells and readily exit the endosome into the soma. We now show that use of a polyampholyte coating [in which the neutral PEG is replaced by the negatively heterocharged CL4 (compact ligand], results in the specific targeting of the palmitoylated peptide to neurons in mature rat hippocampal slice cultures. There was no noticeable uptake by astrocytes, oligodendrocytes or microglia (identified by immunocytochemistry, demonstrating neuronal specificity to the overall negatively charged CL4 coating. In addition, EM (electron microscopy images confirm the endosomal egress ability of the Palm1 peptide by showing a much more disperse cytosolic distribution of the CL4 QDs conjugated to Palm1 compared with CL4 QDs alone. This suggests a novel and robust way of delivering neurotherapeutics to neurons.

  6. Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network

    Science.gov (United States)

    Kaplan, Raphael; Adhikari, Mohit H.; Hindriks, Rikkert; Mantini, Dante; Murayama, Yusuke; Logothetis, Nikos K.; Deco, Gustavo

    2016-01-01

    Summary The default mode network (DMN) is a commonly observed resting-state network (RSN) that includes medial temporal, parietal, and prefrontal regions involved in episodic memory [1, 2, 3]. The behavioral relevance of endogenous DMN activity remains elusive, despite an emerging literature correlating resting fMRI fluctuations with memory performance [4, 5]—particularly in DMN regions [6, 7, 8]. Mechanistic support for the DMN’s role in memory consolidation might come from investigation of large deflections (sharp-waves) in the hippocampal local field potential that co-occur with high-frequency (>80 Hz) oscillations called ripples—both during sleep [9, 10] and awake deliberative periods [11, 12, 13]. Ripples are ideally suited for memory consolidation [14, 15], since the reactivation of hippocampal place cell ensembles occurs during ripples [16, 17, 18, 19]. Moreover, the number of ripples after learning predicts subsequent memory performance in rodents [20, 21, 22] and humans [23], whereas electrical stimulation of the hippocampus after learning interferes with memory consolidation [24, 25, 26]. A recent study in macaques showed diffuse fMRI neocortical activation and subcortical deactivation specifically after ripples [27]. Yet it is unclear whether ripples and other hippocampal neural events influence endogenous fluctuations in specific RSNs—like the DMN—unitarily. Here, we examine fMRI datasets from anesthetized monkeys with simultaneous hippocampal electrophysiology recordings, where we observe a dramatic increase in the DMN fMRI signal following ripples, but not following other hippocampal electrophysiological events. Crucially, we find increases in ongoing DMN activity after ripples, but not in other RSNs. Our results relate endogenous DMN fluctuations to hippocampal ripples, thereby linking network-level resting fMRI fluctuations with behaviorally relevant circuit-level neural dynamics. PMID:26898464

  7. Effects of chronic prenatal ethanol exposure on locomotor activity, and hippocampal weight, neurons, and nitric oxide synthase activity of the young postnatal guinea pig.

    Science.gov (United States)

    Gibson, M A; Butters, N S; Reynolds, J N; Brien, J F

    2000-01-01

    Decreased nitric oxide synthase (NOS)-catalyzed formation of NO from L-arginine may be involved in ethanol teratogenesis involving the hippocampus. This hypothesis was tested by determining the effects of chronic prenatal ethanol exposure on locomotor activity and on hippocampal weight, number of CA1 and CA3 pyramidal cells and dentate gyrus granule cells, and NOS activity of the postnatal guinea pig. Timed, pregnant guinea pigs received one of the following chronic oral regimens throughout gestation: 4 g ethanol/kg maternal body weight/day, isocaloric-sucrose/pair-feeding, or water. At postnatal day (PD) 10, spontaneous locomotor activity was measured. At PD 12, histological analysis was performed on the hippocampal formation, in which hippocampal CA1 and CA3 pyramidal cells and dentate gyrus granule cells were counted; body, brain, and hippocampal weights were measured; and hippocampal NOS enzymatic activity was determined using a radiometric assay. Chronic prenatal ethanol exposure produced hyperactivity, decreased the brain and hippocampal weights with no change in body weight, decreased the number of hippocampal CA1 pyramidal cells by 25-30%, and had no effect on hippocampal NOS activity compared with the two control groups. These data, together with our previous findings in the fetal guinea pig, demonstrate that chronic prenatal ethanol exposure decreases hippocampal NOS activity in near-term fetal life that temporally precedes the selective loss of hippocampal CA1 pyramidal cells in postnatal life. PMID:10758347

  8. Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies.

    Science.gov (United States)

    Giovanoli, Sandra; Weber-Stadlbauer, Ulrike; Schedlowski, Manfred; Meyer, Urs; Engler, Harald

    2016-07-01

    Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre- and postsynaptic deficits. Using a well-established mouse model of maternal exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)-exposed and control mothers. We found that prenatal immune activation induced an adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early-life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial anomalies or systemic inflammation, adult offspring exposed to prenatal immune activation displayed increased hippocampal IL-1β levels. Taken together, our findings demonstrate that age-dependent synaptic deficits and abnormal pro-inflammatory cytokine expression can occur during postnatal brain maturation in the absence of microglial anomalies or systemic inflammation. PMID:26408796

  9. APP Is a Context-Sensitive Regulator of the Hippocampal Presynaptic Active Zone.

    Science.gov (United States)

    Laßek, Melanie; Weingarten, Jens; Wegner, Martin; Mueller, Benjamin F; Rohmer, Marion; Baeumlisberger, Dominic; Arrey, Tabiwang N; Hick, Meike; Ackermann, Jörg; Acker-Palmer, Amparo; Koch, Ina; Müller, Ulrike; Karas, Michael; Volknandt, Walter

    2016-04-01

    The hallmarks of Alzheimer's disease (AD) are characterized by cognitive decline and behavioral changes. The most prominent brain region affected by the progression of AD is the hippocampal formation. The pathogenesis involves a successive loss of hippocampal neurons accompanied by a decline in learning and memory consolidation mainly attributed to an accumulation of senile plaques. The amyloid precursor protein (APP) has been identified as precursor of Aβ-peptides, the main constituents of senile plaques. Until now, little is known about the physiological function of APP within the central nervous system. The allocation of APP to the proteome of the highly dynamic presynaptic active zone (PAZ) highlights APP as a yet unknown player in neuronal communication and signaling. In this study, we analyze the impact of APP deletion on the hippocampal PAZ proteome. The native hippocampal PAZ derived from APP mouse mutants (APP-KOs and NexCreAPP/APLP2-cDKOs) was isolated by subcellular fractionation and immunopurification. Subsequently, an isobaric labeling was performed using TMT6 for protein identification and quantification by high-resolution mass spectrometry. We combine bioinformatics tools and biochemical approaches to address the proteomics dataset and to understand the role of individual proteins. The impact of APP deletion on the hippocampal PAZ proteome was visualized by creating protein-protein interaction (PPI) networks that incorporated APP into the synaptic vesicle cycle, cytoskeletal organization, and calcium-homeostasis. The combination of subcellular fractionation, immunopurification, proteomic analysis, and bioinformatics allowed us to identify APP as structural and functional regulator in a context-sensitive manner within the hippocampal active zone network. PMID:27092780

  10. APP Is a Context-Sensitive Regulator of the Hippocampal Presynaptic Active Zone.

    Directory of Open Access Journals (Sweden)

    Melanie Laßek

    2016-04-01

    Full Text Available The hallmarks of Alzheimer's disease (AD are characterized by cognitive decline and behavioral changes. The most prominent brain region affected by the progression of AD is the hippocampal formation. The pathogenesis involves a successive loss of hippocampal neurons accompanied by a decline in learning and memory consolidation mainly attributed to an accumulation of senile plaques. The amyloid precursor protein (APP has been identified as precursor of Aβ-peptides, the main constituents of senile plaques. Until now, little is known about the physiological function of APP within the central nervous system. The allocation of APP to the proteome of the highly dynamic presynaptic active zone (PAZ highlights APP as a yet unknown player in neuronal communication and signaling. In this study, we analyze the impact of APP deletion on the hippocampal PAZ proteome. The native hippocampal PAZ derived from APP mouse mutants (APP-KOs and NexCreAPP/APLP2-cDKOs was isolated by subcellular fractionation and immunopurification. Subsequently, an isobaric labeling was performed using TMT6 for protein identification and quantification by high-resolution mass spectrometry. We combine bioinformatics tools and biochemical approaches to address the proteomics dataset and to understand the role of individual proteins. The impact of APP deletion on the hippocampal PAZ proteome was visualized by creating protein-protein interaction (PPI networks that incorporated APP into the synaptic vesicle cycle, cytoskeletal organization, and calcium-homeostasis. The combination of subcellular fractionation, immunopurification, proteomic analysis, and bioinformatics allowed us to identify APP as structural and functional regulator in a context-sensitive manner within the hippocampal active zone network.

  11. Cortisol's effects on hippocampal activation in depressed patients are related to alterations in memory formation.

    Science.gov (United States)

    Abercrombie, Heather C; Jahn, Allison L; Davidson, Richard J; Kern, Simone; Kirschbaum, Clemens; Halverson, Jerry

    2011-01-01

    Many investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response to exogenously manipulated cortisol elevations has not yet been directly examined in depressed humans. Animal research shows that glucocorticoids have robust effects on hippocampal function, and can either enhance or suppress neuroplastic events in the hippocampus depending on a number of factors. We hypothesized that depressed individuals would show 1) altered hippocampal response to exogenous administration of cortisol, and 2) altered effects of cortisol on learning. In a repeated-measures design, 19 unmedicated depressed and 41 healthy individuals completed two fMRI scans. Fifteen mg oral hydrocortisone (i.e., cortisol) or placebo (order randomized and double-blind) was administered 1 h prior to encoding of emotional and neutral words during fMRI scans. Data analysis examined the effects of cortisol administration on 1) brain activation during encoding, and 2) subsequent free recall for words. Cortisol affected subsequent recall performance in depressed but not healthy individuals. We found alterations in hippocampal response to cortisol in depressed women, but not in depressed men (who showed altered response to cortisol in other regions, including subgenual prefrontal cortex). In both depressed men and women, cortisol's effects on hippocampal function were positively correlated with its effects on recall performance assessed days later. Our data provide evidence that in depressed compared to healthy women, cortisol's effects on hippocampal function are altered. Our data also show that in both depressed men and women, cortisol's effects on emotional memory formation and hippocampal function are related.

  12. Effects of active shock avoidance learning on hippocampal neurogenesis and plasma levels of corticosterone

    NARCIS (Netherlands)

    van der Borght, Karin; Meerlo, Peter; Luiten, Paul G.M.; Eggen, Bart J.L.; van der Zee, Eddy A.

    2005-01-01

    Hippocampal granule neurons that are newly formed during adulthood might be involved in learning and memory processes. Experimental data suggest that only hippocampus-dependent learning tasks stimulate neurogenesis. To further address this issue, the effects of active shock avoidance (ASA) learning

  13. Hippocampal activity during transient respiratory events in the freely behaving cat

    DEFF Research Database (Denmark)

    Poe, G R; Kristensen, Morten Pilgaard; Rector, D M;

    1996-01-01

    We measured dorsal hippocampal activity accompanying sighs and apnea using reflectance imaging and electrophysiologic measures in freely behaving cats. Reflected 660-nm light from a 1-mm2 area of CA1 was captured during sighs and apnea at 25 Hz through a coherent image conduit coupled to a charge...

  14. Adaptive top-down suppression of hippocampal activity and the purging of intrusive memories from consciousness.

    Science.gov (United States)

    Benoit, Roland G; Hulbert, Justin C; Huddleston, Ean; Anderson, Michael C

    2015-01-01

    When reminded of unwanted memories, people often attempt to suppress these experiences from awareness. Prior work indicates that control processes mediated by the dorsolateral prefrontal cortex (DLPFC) modulate hippocampal activity during such retrieval suppression. It remains unknown whether this modulation plays a role in purging an intrusive memory from consciousness. Here, we combined fMRI and effective connectivity analyses with phenomenological reports to scrutinize a role for adaptive top-down suppression of hippocampal retrieval processes in terminating mnemonic awareness of intrusive memories. Participants either suppressed or recalled memories of pictures depicting faces or places. After each trial, they reported their success at regulating awareness of the memory. DLPFC activation was greatest when unwanted memories intruded into consciousness and needed to be purged, and this increased engagement predicted superior control of intrusive memories over time. However, hippocampal activity was decreased during the suppression of place memories only. Importantly, the inhibitory influence of the DLPFC on the hippocampus was linked to the ensuing reduction in intrusions of the suppressed memories. Individuals who exhibited negative top-down coupling during early suppression attempts experienced fewer involuntary memory intrusions later on. Over repeated suppressions, the DLPFC-hippocampus connectivity grew less negative with the degree that they no longer had to purge unwanted memories from awareness. These findings support a role of DLPFC in countermanding the unfolding recollection of an unwanted memory via the suppression of hippocampal processing, a mechanism that may contribute to adaptation in the aftermath of traumatic experiences. PMID:25100219

  15. Fractal analysis of a voltage-dependent potassium channel from cultured mouse hippocampal neurons.

    Science.gov (United States)

    Liebovitch, L S; Sullivan, J M

    1987-12-01

    The kinetics of ion channels have been widely modeled as a Markov process. In these models it is assumed that the channel protein has a small number of discrete conformational states and the kinetic rate constants connecting these states are constant. In the alternative fractal model the spontaneous fluctuations of the channel protein at many different time scales are represented by a kinetic rate constant k = At1-D, where A is the kinetic setpoint and D the fractal dimension. Single-channel currents were recorded at 146 mM external K+ from an inwardly rectifying, 120 pS, K+ selective, voltage-sensitive channel in cultured mouse hippocampal neurons. The kinetics of these channels were found to be statistically self-similar at different time scales as predicted by the fractal model. The fractal dimensions were approximately 2 for the closed times and approximately 1 for the open times and did not depend on voltage. For both the open and closed times the logarithm of the kinetic setpoint was found to be proportional to the applied voltage, which indicates that the gating of this channel involves the net inward movement of approximately one negative charge when this channel opens. Thus, the open and closed times and the voltage dependence of the gating of this channel are well described by the fractal model. PMID:2447974

  16. Tracking burst patterns in hippocampal cultures with high-density CMOS-MEAs

    Science.gov (United States)

    Gandolfo, M.; Maccione, A.; Tedesco, M.; Martinoia, S.; Berdondini, L.

    2010-10-01

    In this work, we investigate the spontaneous bursting behaviour expressed by in vitro hippocampal networks by using a high-resolution CMOS-based microelectrode array (MEA), featuring 4096 electrodes, inter-electrode spacing of 21 µm and temporal resolution of 130 µs. In particular, we report an original development of an adapted analysis method enabling us to investigate spatial and temporal patterns of activity and the interplay between successive network bursts (NBs). We first defined and detected NBs, and then, we analysed the spatial and temporal behaviour of these events with an algorithm based on the centre of activity trajectory. We further refined the analysis by using a technique derived from statistical mechanics, capable of distinguishing the two main phases of NBs, i.e. (i) a propagating and (ii) a reverberating phase, and by classifying the trajectory patterns. Finally, this methodology was applied to signal representations based on spike detection, i.e. the instantaneous firing rate, and directly based on voltage-coded raw data, i.e. activity movies. Results highlight the potentialities of this approach to investigate fundamental issues on spontaneous neuronal dynamics and suggest the hypothesis that neurons operate in a sort of 'team' to the perpetuation of the transmission of the same information.

  17. Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression.

    Science.gov (United States)

    Huijbers, Willem; Mormino, Elizabeth C; Schultz, Aaron P; Wigman, Sarah; Ward, Andrew M; Larvie, Mykol; Amariglio, Rebecca E; Marshall, Gad A; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A

    2015-04-01

    Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity--consistent with findings in genetic at-risk populations--and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer's disease continuum. Here, we examine the contribution of amyloid-β deposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model

  18. Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression

    Science.gov (United States)

    Mormino, Elizabeth C.; Schultz, Aaron P.; Wigman, Sarah; Ward, Andrew M.; Larvie, Mykol; Amariglio, Rebecca E.; Marshall, Gad A.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.

    2015-01-01

    Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity—consistent with findings in genetic at-risk populations—and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer’s disease continuum. Here, we examine the contribution of amyloid-β deposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model

  19. Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning

    Directory of Open Access Journals (Sweden)

    Miriam Shirin Nokia

    2012-12-01

    Full Text Available Oscillations in hippocampal local-field potentials reflect the crucial involvement of the hippocampus in memory trace formation: theta (4-8 Hz oscillations and ripples (~200 Hz occurring during sharp waves are thought to mediate encoding and consolidation, respectively. During sharp wave-ripple complexes (SPW-Rs, hippocampal cell firing closely follows the pattern that took place during the initial experience, most likely reflecting replay of that event. Disrupting hippocampal ripples using electrical stimulation either during training in awake animals or during sleep after training retards spatial learning. Here, adult rabbits were trained in trace eyeblink conditioning, a hippocampus-dependent associative learning task. A bright light was presented to the animals during the inter-trial interval, when awake, either during SPW-Rs or irrespective of their neural state. Learning was particularly poor when the light was presented following SPW-Rs. While the light did not disrupt the ripple itself, it elicited a theta-band oscillation, a state that does not usually coincide with SPW-Rs. Thus, it seems that consolidation depends on neuronal activity within and beyond the hippocampus taking place immediately after, but by no means limited to, hippocampal SPW-Rs.

  20. Membrane voltage modulates the GABA(A) receptor gating in cultured rat hippocampal neurons.

    Science.gov (United States)

    Pytel, Maria; Mercik, Katarzyna; Mozrzymas, Jerzy W

    2006-02-01

    The kinetics of GABAergic currents in neurons is known to be modulated by the membrane voltage but the underlying mechanisms have not been fully explored. In particular, the impact of membrane potential on the GABA(A) receptor gating has not been elucidated. In the present study, the effect of membrane voltage on current responses elicited by ultrafast GABA applications was studied in cultured hippocampal neurons. The current to voltage relationship (I-V) for responses to saturating [GABA] (10 mM) showed an inward rectification (slope conductance at positive voltages was 0.62 +/- 0.05 of that at negative potentials). On the contrary, I-V for currents evoked by low [GABA] (1 microM) showed an outward rectification. The onset of currents elicited by saturating [GABA] was significantly accelerated at positive potentials. Analysis of currents evoked by prolonged applications of saturating [GABA] revealed that positive voltages significantly increased the rate and extent of desensitization. The onsets of current responses to non-saturating [GABA] were significantly accelerated at positive voltages indicating an enhancement of the binding rate. However, at low [GABA] at which the onset rate is expected to approach an asymptote set by opening/closing and unbinding rates, no significant modification of current onset by voltage was observed. Quantitative analysis based on model simulations indicated that the major effect of membrane depolarization was to increase the rates of binding, desensitization and of opening as well as to slightly reduce the rate of exit from desensitization. In conclusion, we provide evidence that membrane voltage affects the GABA(A) receptor microscopic gating.

  1. Sub-toxic Ethanol Exposure Modulates Gene Expression and Enzyme Activity of Antioxidant Systems to Provide Neuroprotection in Hippocampal HT22 Cells

    Science.gov (United States)

    Casañas-Sánchez, Verónica; Pérez, José A.; Quinto-Alemany, David; Díaz, Mario

    2016-01-01

    Ethanol is known to cause severe systemic damage often explained as secondary to oxidative stress. Brain is particularly vulnerable to ethanol-induced reactive oxygen species (ROS) because the high amounts of lipids, and because nerve cell membranes contain high amounts of peroxidable fatty acids. Usually these effects of ethanol are associated to high and/or chronic exposure to ethanol. However, as we show in this manuscript, a low and acute dose of ethanol trigger a completely different response in hippocampal cells. Thus, we have observed that 0.1% ethanol exposure to HT22 cells, a murine hippocampal-derived cell line, increases the transcriptional expression of different genes belonging to the classical, glutathione/glutaredoxin and thioredoxin/peroxiredoxin antioxidant systems, these including Sod1, Sod2, Gpx1, Gclc, and Txnrd1. Paralleling these changes, enzyme activities of total superoxide dismutase (tSOD), catalase, total glutathione peroxidase (tGPx), glutathione-S-reductase (GSR), and total thioredoxin reductase (tTXNRD), were all increased, while the generation of thiobarbituric acid reactive substances (TBARS), as indicators of lipid peroxidation, and glutathione levels remained unaltered. Ethanol exposure did not affect cell viability or cell growing as assessed by real-time cell culture monitoring, indicating that low ethanol doses are not deleterious for hippocampal cells, but rather prevented glutamate-induced excitotoxicity. In summary, we conclude that sub-toxic exposure to ethanol may well be neuroprotective against oxidative insults in hippocampal cells. PMID:27512374

  2. Large-scale, high-resolution multielectrode-array recording depicts functional network differences of cortical and hippocampal cultures.

    Directory of Open Access Journals (Sweden)

    Shinya Ito

    Full Text Available Understanding the detailed circuitry of functioning neuronal networks is one of the major goals of neuroscience. Recent improvements in neuronal recording techniques have made it possible to record the spiking activity from hundreds of neurons simultaneously with sub-millisecond temporal resolution. Here we used a 512-channel multielectrode array system to record the activity from hundreds of neurons in organotypic cultures of cortico-hippocampal brain slices from mice. To probe the network structure, we employed a wavelet transform of the cross-correlogram to categorize the functional connectivity in different frequency ranges. With this method we directly compare, for the first time, in any preparation, the neuronal network structures of cortex and hippocampus, on the scale of hundreds of neurons, with sub-millisecond time resolution. Among the three frequency ranges that we investigated, the lower two frequency ranges (gamma (30-80 Hz and beta (12-30 Hz range showed similar network structure between cortex and hippocampus, but there were many significant differences between these structures in the high frequency range (100-1000 Hz. The high frequency networks in cortex showed short tailed degree-distributions, shorter decay length of connectivity density, smaller clustering coefficients, and positive assortativity. Our results suggest that our method can characterize frequency dependent differences of network architecture from different brain regions. Crucially, because these differences between brain regions require millisecond temporal scales to be observed and characterized, these results underscore the importance of high temporal resolution recordings for the understanding of functional networks in neuronal systems.

  3. Role of neuronal Ras activity in adult hippocampal neurogenesis and cognition

    Directory of Open Access Journals (Sweden)

    Martina eManns

    2011-02-01

    Full Text Available Hippocampal neurogenesis in the adult mammalian brain is modulated by various signals like growth factors, hormones, neuropeptides, and neurotransmitters. All of these factors can (but not necessarily do converge on the activation of the G protein p21Ras. We used a transgenic mouse model (synRas mice expressing constitutively activated G12V-Harvey Ras selectively in differentiated neurons to investigate the possible effects onto neurogenesis. Ras activation in neurons attenuates hippocampal precursor cell generation at an early stage of the proliferative cascade before neuronal lineage determination occurs. Therefore it is unlikely that the transgenically activated Ras in neurons mediates this effect by a direct, intracellular signaling mechanism. Voluntary exercise restores neurogenesis up to wild type level presumably mediated by brain derived neurotrophic factor. Reduced neurogenesis is linked to impairments in spatial short-term memory and object recognition, the latter can be rescued by voluntary exercise, as well. These data support the view that new cells significantly increase complexity that can be processed by the hippocampal network when experience requires high demands to associate stimuli over time and/or space.

  4. Autobiographical Memory Retrieval and Hippocampal Activation as a Function of Repetition and the Passage of Time

    Directory of Open Access Journals (Sweden)

    Lynn Nadel

    2007-01-01

    Full Text Available Multiple trace theory (MTT predicts that hippocampal memory traces expand and strengthen as a function of repeated memory retrievals. We tested this hypothesis utilizing fMRI, comparing the effect of memory retrieval versus the mere passage of time on hippocampal activation. While undergoing fMRI scanning, participants retrieved remote autobiographical memories that had been previously retrieved either one month earlier, two days earlier, or multiple times during the preceding month. Behavioral analyses revealed that the number and consistency of memory details retrieved increased with multiple retrievals but not with the passage of time. While all three retrieval conditions activated a similar set of brain regions normally associated with autobiographical memory retrieval including medial temporal lobe structures, hippocampal activation did not change as a function of either multiple retrievals or the passage of time. However, activation in other brain regions, including the precuneus, lateral prefrontal cortex, parietal cortex, lateral temporal lobe, and perirhinal cortex increased after multiple retrievals, but was not influenced by the passage of time. These results have important implications for existing theories of long-term memory consolidation.

  5. Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat.

    Science.gov (United States)

    Ego-Stengel, Valérie; Wilson, Matthew A

    2010-01-01

    The hippocampus plays a key role in the acquisition of new memories for places and events. Evidence suggests that the consolidation of these memories is enhanced during sleep. At the neuronal level, reactivation of awake experience in the hippocampus during sharp-wave ripple events, characteristic of slow-wave sleep, has been proposed as a neural mechanism for sleep-dependent memory consolidation. However, a causal relation between sleep reactivation and memory consolidation has not been established. Here we show that disrupting neuronal activity during ripple events impairs spatial learning. We trained rats daily in two identical spatial navigation tasks followed each by a 1-hour rest period. After one of the tasks, stimulation of hippocampal afferents selectively disrupted neuronal activity associated with ripple events without changing the sleep-wake structure. Rats learned the control task significantly faster than the task followed by rest stimulation, indicating that interfering with hippocampal processing during sleep led to decreased learning.

  6. Hippocampal Cannabinoid Transmission Modulates Dopamine Neuron Activity: Impact on Rewarding Memory Formation and Social Interaction

    OpenAIRE

    Loureiro, Michael; Renard, Justine; Zunder, Jordan; Laviolette, Steven R

    2015-01-01

    Disturbances in cannabinoid type 1 receptor (CB1R) signaling have been linked to emotional and cognitive deficits characterizing neuropsychiatric disorders, including schizophrenia. Thus, there is growing interest in characterizing the relationship between cannabinoid transmission, emotional processing, and dopamine (DA)-dependent behavioral deficits. The CB1R is highly expressed in the mammalian nervous system, particularly in the hippocampus. Activation of the ventral hippocampal subregion ...

  7. Hippocampal sub-regional shape and physical activity in older adults.

    Science.gov (United States)

    Varma, Vijay R; Tang, Xiaoying; Carlson, Michelle C

    2016-08-01

    Hippocampal atrophy is a hallmark of Alzheimer's disease pathology, and a target biomarker region for testing intervention efficacy. Over the last few decades, a growing body of evidence from animal and human models suggests that physical activity (PA) is associated with structural benefits to the hippocampus in older adults. Very few human studies, however have explored hippocampal sub-regional specificity of PA; this is significant considering that sub-regions of the hippocampus are associated with distinct cognitive tasks and are differentially affected by disease pathology. This study used objective and self-reported measures of daily walking activity and exercise, and surface-based regional shape analysis using high-field hippocampal sub-regional partitions to explore sub-region specific hippocampal associations in a sample of nondemented, community-dwelling older adults at elevated sociodemographic risk for cognitive decline. Vertex-wise surface areas, which may be more sensitive than global volume measures, were calculated using shape diffeomorphometry, and PA was assessed using step activity monitors and PA questionnaires. We found that daily walking activity in a participant's environment was associated in cross-section mainly with larger surface areas of the subiculum in women. Associations remained significant when controlling for self-reported exercise. Prior studies have found that PA related to exercise and aerobic fitness may be most closely associated with the anterior hippocampus, particularly the dentate gyrus of the hippocampus. These novel findings are the first, to our knowledge, in human models to suggest that PA related to navigation that may not reach the level of moderate-intensity exercise may be associated with specific sub-regions of the hippocampus. These findings underscore the importance of better understanding the independent and related biological mechanisms and pathways by which increasing exercise as well as non

  8. Modulation of inhibitory glycine receptors in cultured embryonic mouse hippocampal neurons by zinc, thiol containing redox agents and carnosine.

    Science.gov (United States)

    Thio, L L; Zhang, H X

    2006-01-01

    Modulation of inhibitory glycine receptors by zinc (Zn(2+)) and endogenous redox agents such as glutathione may alter inhibition in the mammalian brain. Despite the abundance of Zn(2+) in the hippocampus and its ability to modulate glycine receptors, few studies have examined Zn(2+) modulation of hippocampal glycine receptors. Whether redox agents modulate hippocampal glycine receptors also remains unknown. This study examined Zn(2+) and redox modulation of glycine receptor-mediated currents in cultured embryonic mouse hippocampal neurons using whole-cell recordings. Zn(2+) concentrations below 10 microM potentiated currents elicited by low glycine, beta-alanine, and taurine concentrations by 300-400%. Zn(2+) concentrations above 300 microM produced nearly complete inhibition. Potentiating Zn(2+) concentrations shifted the dose-response curves for the three agonists to the left and decreased the Hill coefficient for glycine and beta-alanine but not taurine. Inhibiting Zn(2+) concentrations shifted the dose-response curves for glycine and beta-alanine to the right but reduced the maximum taurine response. Histidine residues may participate in potentiation because diethyl pyrocarbonate and pH 5.4 diminished Zn(2+) enhancement of glycine currents. pH 5.4 diminished Zn(2+) block of glycine currents, but diethyl pyrocarbonate did not. These findings indicate that separate sites mediate Zn(2+) potentiation and inhibition. The redox agents glutathione, dithiothreitol, tris(2-carboxyethyl)phosphine, and 5,5'-dithiobis(2-nitrobenzoic acid) did not alter glycine currents by a redox mechanism. However, glutathione and dithiothreitol interfered with the effects of Zn(2+) on glycine currents by chelating it. Carnosine had similar effects. Thus, Zn(2+) and thiol containing redox agents that chelate Zn(2+) modulate hippocampal glycine receptors with the mechanism of Zn(2+) modulation being agonist dependent. PMID:16515845

  9. 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

  10. Impairment of cognitive function and reduced hippocampal cholinergic activity in a rat model of chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    Chunling Zhao; Yan Chen; Chunlai Zhang; Linya Lü; Qian Xu

    2011-01-01

    The present study established a rat model of chronic intermittent hypoxia (CIH) to simulate obstructive sleep apnea syndrome. CIH rats were evaluated for cognitive function using the Morris water maze, and neuronal pathology in the hippocampus was observed using hematoxylin-eosin staining. In addition, hippocampal choline acetyl transferase (ChAT) and nicotinic acetylcholine receptor (nAChR) expression was determined by immunohistochemistry. Our results revealed necrotic hippocampal neurons, decreased ChAT and nAChR expression, as well as cognitive impairment in CIH rats. These results suggest that hippocampal neuronal necrosis and decreased cholinergic activity may be involved in CIH-induced cognitive impairment in rats.

  11. Social and cultural activities

    CERN Multimedia

    2008-01-01

    Club news : Record Club, Ski Club, Dancing Club, Orienteering Club, CERN Women's Club, Concerts Club, Russian Cultural Circle, Yachting Club. Conference : Voyage au coeur d'une flûte de champagne. Exhibition.

  12. MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process

    Science.gov (United States)

    Huang, Hao; Zhou, Xin; Liu, Xi; Xu, Tao; Ma, Limin

    2016-01-01

    Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (miR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether miR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model. Silencing miR-132 inhibited the electrical excitability level of cultured epileptic neurons, whereas silencing p250GAP had an opposite effect. In addition, we verified the effect of miR-132 in vivo and found that silencing miR-132 inhibited the aberrant formation of dendritic spines and chronic spontaneous seizure in a lithium-pilocarpine-induced epileptic mouse model. Finally, we confirmed that silencing miR-132 has a neuroprotective effect on cultured epileptic neurons; however, this effect did not occur through the p250GAP pathway. Generally, silencing miR-132 may suppress spontaneous seizure activity through the miR-132/p250GAP/Cdc42 pathway by regulating the morphology and electrophysiology of dendritic spines; therefore, miR-132 may serve as a potential target for the development of antiepileptic drugs.

  13. MicroRNA-132 Interact with p250GAP/Cdc42 Pathway in the Hippocampal Neuronal Culture Model of Acquired Epilepsy and Associated with Epileptogenesis Process.

    Science.gov (United States)

    Yuan, Jinxian; Huang, Hao; Zhou, Xin; Liu, Xi; Ou, Shu; Xu, Tao; Li, Ruohan; Ma, Limin; Chen, Yangmei

    2016-01-01

    Increasing evidence suggests that epilepsy is the result of synaptic reorganization and pathological excitatory loop formation in the central nervous system; however, the mechanisms that regulate this process are not well understood. We proposed that microRNA-132 (miR-132) and p250GAP might play important roles in this process by activating the downstream Rho GTPase family. We tested this hypothesis using a magnesium-free medium-induced epileptic model of cultured hippocampal neurons. We investigated whether miR-132 regulates GTPase activity through p250GAP and found that Cdc42 was significantly activated in our experimental model. Silencing miR-132 inhibited the electrical excitability level of cultured epileptic neurons, whereas silencing p250GAP had an opposite effect. In addition, we verified the effect of miR-132 in vivo and found that silencing miR-132 inhibited the aberrant formation of dendritic spines and chronic spontaneous seizure in a lithium-pilocarpine-induced epileptic mouse model. Finally, we confirmed that silencing miR-132 has a neuroprotective effect on cultured epileptic neurons; however, this effect did not occur through the p250GAP pathway. Generally, silencing miR-132 may suppress spontaneous seizure activity through the miR-132/p250GAP/Cdc42 pathway by regulating the morphology and electrophysiology of dendritic spines; therefore, miR-132 may serve as a potential target for the development of antiepileptic drugs. PMID:27579184

  14. Formaldehyde increases intracellular calcium concentration in primary cultured hippocampal neurons partly through NMDA receptors and T-type calcium channels

    Institute of Scientific and Technical Information of China (English)

    Ye-Nan Chi; Xu Zhang; Jie Cai; Feng-Yu Liu; Guo-Gang Xing; You Wan

    2012-01-01

    Objective Formaldehyde at high concentrations is a contributor to air pollution.It is also an endogenous metabolic product in cells,and when beyond physiological concentrations,has pathological effects on neurons.Formaldehyde induces mis-folding and aggregation of neuronal tau protein,hippocampal neuronal apoptosis,cognitive impairment and loss of memory functions,as well as excitation of peripheral nociceptive neurons in cancer pain models.Intracellular calcium ([Ca2+]i) is an important intracellular messenger,and plays a key role in many pathological processes.The present study aimed to investigate the effect of formaldehyde on [Ca2+]i and the possible involvement of N-methyl-D-aspartate receptors (NMDARs) and T-type Ca2+ channels on the cell membrane.Methods Using primary cultured hippocampal neurons as a model,changes of [Ca2+]i in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy.Results Formaldehyde at 1 mmol/L approximately doubled [Ca2+]i.(2R)-amino-5-phosphonopentanoate (AP5,25 μtmol/L,an NMDAR antagonist) and mibefradil (MIB,1 μtmol/L,a T-type Ca2+ channel blocker),given 5 min after formaldehyde perfusion,each partly inhibited the formaldehyde-induced increase of [Ca2+]i,and this inhibitory effect was reinforced by combined application of AP5 and MIB.When applied 3 min before formaldehyde perfusion,AP5 (even at 50 μmol/L) did not inhibit the formaldehyde-induced increase of [Ca2+]i,but MIB (1 μmol/L) significantly inhibited this increase by 70%.Conclusion These results suggest that formaldehyde at a low concentration increases [Ca2+]i in cultured hippocampal neurons; NMDARs and T-type Ca2+ channels may be involved in this process.

  15. Kynurenine pathway metabolites are associated with hippocampal activity during autobiographical memory recall in patients with depression.

    Science.gov (United States)

    Young, Kymberly D; Drevets, Wayne C; Dantzer, Robert; Teague, T Kent; Bodurka, Jerzy; Savitz, Jonathan

    2016-08-01

    Inflammation-related changes in the concentrations of inflammatory mediators such as c-reactive protein (CRP), interleukin 1β (IL-1), and IL-6 as well as kynurenine metabolites are associated with major depressive disorder (MDD) and affect depressive behavior, cognition, and hippocampal plasticity in animal models. We previously reported that the ratios of kynurenic acid (KynA) to the neurotoxic metabolites, 3-hydroxykynurenine (3HK) and quinolinic acid (QA), were positively correlated with hippocampal volume in depression. The hippocampus is critical for autobiographical memory (AM) recall which is impaired in MDD. Here we tested whether the ratios, KynA/3HK and KynA/QA were associated with AM recall performance as well as hippocampal activity during AM recall. Thirty-five unmedicated depressed participants and 25 healthy controls (HCs) underwent fMRI scanning while recalling emotionally-valenced AMs and provided serum samples for the quantification of kynurenine metabolites, CRP, and cytokines (IL-1 receptor antagonist - IL-1RA; IL-6, tumor necrosis factor alpha - TNF, interferon gamma -IFN-γ, IL-10). KynA/3HK and KynA/QA were lower in the MDD group relative to the HCs. The concentrations of the CRP and the cytokines did not differ significantly between the HCs and the MDD group. Depressed individuals recalled fewer specific AMs and displayed increased left hippocampal activity during the recall of positive and negative memories. KynA/3HK was inversely associated with left hippocampal activity during specific AM recall in the MDD group. Further, KynA/QA was positively correlated with percent negative specific memories recalled in the MDD group and showed a non-significant trend toward a positive correlation with percent positive specific memories recalled in HCs. In contrast, neither CRP nor the cytokines were significantly associated with AM recall or activity of the hippocampus during AM recall. Conceivably, an imbalance in levels of KynA versus QA

  16. Key physiological parameters dictate triggering of activity-dependent bulk endocytosis in hippocampal synapses.

    Directory of Open Access Journals (Sweden)

    Eva M Wenzel

    Full Text Available To maintain neurotransmission in central neurons, several mechanisms are employed to retrieve synaptically exocytosed membrane. The two major modes of synaptic vesicle (SV retrieval are clathrin-mediated endocytosis and activity-dependent bulk endocytosis (ADBE. ADBE is the dominant SV retrieval mode during intense stimulation, however the precise physiological conditions that trigger this mode are not resolved. To determine these parameters we manipulated rat hippocampal neurons using a wide spectrum of stimuli by varying both the pattern and duration of stimulation. Using live-cell fluorescence imaging and electron microscopy approaches, we established that stimulation frequency, rather than the stimulation load, was critical in the triggering of ADBE. Thus two hundred action potentials, when delivered at high frequency, were sufficient to induce near maximal bulk formation. Furthermore we observed a strong correlation between SV pool size and ability to perform ADBE. We also identified that inhibitory nerve terminals were more likely to utilize ADBE and had a larger SV recycling pool. Thus ADBE in hippocampal synaptic terminals is tightly coupled to stimulation frequency and is more likely to occur in terminals with large SV pools. These results implicate ADBE as a key modulator of both hippocampal neurotransmission and plasticity.

  17. Acute restraint stress enhances hippocampal endocannabinoid function via glucocorticoid receptor activation.

    Science.gov (United States)

    Wang, Meina; Hill, Matthew N; Zhang, Longhua; Gorzalka, Boris B; Hillard, Cecilia J; Alger, Bradley E

    2012-01-01

    Exposure to behavioural stress normally triggers a complex, multilevel response of the hypothalamic-pituitary-adrenal (HPA) axis that helps maintain homeostatic balance. Although the endocannabinoid (eCB) system (ECS) is sensitive to chronic stress, few studies have directly addressed its response to acute stress. Here we show that acute restraint stress enhances eCB-dependent modulation of GABA release measured by whole-cell voltage clamp of inhibitory postsynaptic currents (IPSCs) in rat hippocampal CA1 pyramidal cells in vitro. Both Ca(2+)-dependent, eCB-mediated depolarization-induced suppression of inhibition (DSI), and muscarinic cholinergic receptor (mAChR)-mediated eCB mobilization are enhanced following acute stress exposure. DSI enhancement is dependent on the activation of glucocorticoid receptors (GRs) and is mimicked by both in vivo and in vitro corticosterone treatment. This effect does not appear to involve cyclooxygenase-2 (COX-2), an enzyme that can degrade eCBs; however, treatment of hippocampal slices with the L-type calcium (Ca(2+)) channel inhibitor, nifedipine, reverses while an agonist of these channels mimics the effect of in vivo stress. Finally, we find that acute stress produces a delayed (by 30 min) increase in the hippocampal content of 2-arachidonoylglycerol, the eCB responsible for DSI. These results support the hypothesis that the ECS is a biochemical effector of glucocorticoids in the brain, linking stress with changes in synaptic strength. PMID:21890595

  18. Membrane voltage differently affects mIPSCs and current responses recorded from somatic excised patches in rat hippocampal cultures.

    Science.gov (United States)

    Pytel, Maria; Mozrzymas, Jerzy W

    2006-01-30

    Recent analysis of current responses to exogenous GABA applications recorded from excised patches indicated that membrane voltage affected the GABAA receptor gating mainly by altering desensitization and binding [M. Pytel, K. Mercik, J.W. Mozrzymas, Membrane voltage modulates the GABAA receptor gating in cultured rat hippocampal neurons, Neuropharmacology, in press]. In order investigate the impact of such voltage effect on GABAA receptors in conditions of synaptic transmission, mIPSCs and current responses to rapid GABA applications were recorded from the same culture of rat hippocampal neurons. We found that I-V relationship for mIPSCs amplitudes showed a clear outward rectification while for current responses an inward rectification was seen, except for very low GABA concentrations. A clear shift in amplitude cumulative distributions indicated that outward rectification resulted from the voltage effect on the majority of mIPSCs. Moreover, the decaying phase of mIPSCs was clearly slowed down at positive voltages and this effect was represented by a shift in cumulative distributions of weighted decaying time constants. In contrast, deactivation of current responses was only slightly affected by membrane depolarization. These data indicate that the mechanisms whereby the membrane voltage modulates synaptic and extrasynaptic receptors are qualitatively different but the mechanism underlying this difference is not clear.

  19. The emergence of spontaneous activity in neuronal cultures

    Science.gov (United States)

    Orlandi, J. G.; Alvarez-Lacalle, E.; Teller, S.; Soriano, J.; Casademunt, J.

    2013-01-01

    In vitro neuronal networks of dissociated hippocampal or cortical tissues are one of the most attractive model systems for the physics and neuroscience communities. Cultured neurons grow and mature, develop axons and dendrites, and quickly connect to their neighbors to establish a spontaneously active network within a week. The resulting neuronal network is characterized by a combination of excitatory and inhibitory neurons coupled through synaptic connections that interact in a highly nonlinear manner. The nonlinear behavior emerges from the dynamics of both the neurons' spiking activity and synaptic transmission, together with biological noise. These ingredients give rise to a rich repertoire of phenomena that are still poorly understood, including the emergence and maintenance of periodic spontaneous activity, avalanches, propagation of fronts and synchronization. In this work we present an overview on the rich activity of cultured neuronal networks, and detail the minimal theoretical considerations needed to describe experimental observations.

  20. Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse.

    Science.gov (United States)

    Tanaka, Masayuki; Yoneyama, Masanori; Shiba, Tatsuo; Yamaguchi, Taro; Ogita, Kiyokazu

    2016-07-01

    Thrombin-activated protease-activated receptor (PAR)-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs) derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR. Direct exposure of the cells to thrombin dramatically attenuated the cell proliferation without causing cell damage. This thrombin-induced attenuation was almost completely abolished by the PAR antagonist RWJ 56110, as well as by dabigatran and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), which are selective and non-selective thrombin inhibitors, respectively. Expectedly, the PAR-1 agonist peptide (AP) SFLLR-NH2 also attenuated the cell proliferation. The cell proliferation was not affected by the PAR-1 negative control peptide RLLFT-NH2, which is an inactive peptide for PAR-1. Independently, we determined the effect of in vivo treatment with AEBSF or AP on hippocampal neurogenesis in the adult mouse. The administration of AEBSF, but not that of AP, significantly increased the number of newly-generated cells in the hippocampal subgranular zone. These data suggest that PAR-1 negatively regulated adult neurogenesis in the hippocampus by inhibiting the proliferative activity of the NPCs. PMID:27426918

  1. SNAP-29-mediated Modulation of Synaptic Transmission in Cultured Hippocampal Neurons*

    OpenAIRE

    Pan, Ping-Yue; Cai, Qian; Lin, Lin; Lu, Pei-Hua; Duan, Shumin; Sheng, Zu-Hang

    2005-01-01

    Identifying the molecules that regulate both the recycling of synaptic vesicles and the SNARE components required for fusion is critical for elucidating the molecular mechanisms underlying synaptic plasticity. SNAP-29 was initially isolated as a syntaxin-binding and ubiquitously expressed protein. Previous studies have suggested that SNAP-29 inhibits SNARE complex disassembly, thereby reducing synaptic transmission in cultured superior cervical ganglion neurons in an activity-dependent manner...

  2. Extremely-low-frequency magnetic fields disrupt rhythmic slow activity in rat hippocampal slices.

    Science.gov (United States)

    Bawin, S M; Satmary, W M; Jones, R A; Adey, W R; Zimmerman, G

    1996-01-01

    Several studies have indicated that weak, extremely-low-frequency (ELF; 1-100 Hz) magnetic fields affect brain electrical activity and memory processes in man and laboratory animals. Our studies sought to determine whether ELF magnetic fields could couple directly with brain tissue and affect neuronal activity in vitro. We used rat hippocampal slices to study field effects on a specific brain activity known as rhythmic slow activity (RSA), or theta rhythm, which occurs in 7-15 s bursts in the hippocampus during memory functions. RSA, which, in vivo, is a cholinergic activity, is induced in hippocampal slices by perfusion of the tissue with carbachol, a stable analog of acetylcholine. We previously demonstrated that the free radical nitric oxide (NO), synthesized in carbachol-treated hippocampal slices, lengthened and destabilized the intervals between successive RSA episodes. Here, we investigate the possibility that sinusoidal ELF magnetic fields could trigger the NO-dependent perturbation of the rate of occurrence of the RSA episodes. Carbachol-treated slices were exposed for 10 min epochs to 1 or 60 Hz magnetic fields with field intensities of 5.6, 56, or 560 microT (rms), or they were sham exposed. All exposures took place in the presence of an ambient DC field of 45 microT, with an angle of -66 degrees from the horizontal plane. Sinusoidal 1 Hz fields at 56 and 560 microT, but not at 5.6 microT, triggered the irreversible destabilization of RSA intervals. Fields at 60 Hz resulted in similar, but not statistically significant, trends. Fields had no effects on RSA when NO synthesis was pharmacologically inhibited. However, field effects could take place when extracellular NO, diffusing from its cell of origin to the extracellular space,was chelated by hemoglobin. These results suggest that ELF magnetic fields exert a strong influence on NO systems in the brain; therefore, they could modulate the functional state of a variety of neuronal ensembles. PMID:8915548

  3. The potential of apolipoprotein E4 to act as a substrate for primary cultures of hippocampal neurons.

    Science.gov (United States)

    Kim, Kwang-Min; Vicenty, Janice; Palmore, G Tayhas R

    2013-04-01

    The E4 isoform of apolipoprotein (apoE4) is known to be a major risk factor for Alzheimer's Disease (AD). Previous in vitro studies have shown apoE4 to have a negative effect on neuronal outgrowth when incubated with lipids. The effect of apoE4 itself on the development of neurons from the central nervous system (CNS), however, has not been well characterized. Consequently, apoE4 alone has not been pursued as a substrate for neuronal cultures. In this study, the effect of surface-bound apoE4 on developmental features of rat hippocampal neurons was examined. We show that apoE4 substrates elicit significantly enhanced values in all developmental features at day 2 of culture when compared to laminin (LN) substrates, which is the current substrate-of-choice for neuronal cultures. Interestingly, the adhesion of hippocampal neurons was found to be significantly lower on LN substrates than on glass substrates, but the axon lengths on both substrates were similar. In addition, this study demonstrates that the adhesion- and growth-enhancing effects of apoE4 substrates are not mediated by heparan sulfate proteoglycans (HSPGs), proteins that have been indicated to function as receptors or co-receptors for apoE4. In the absence of lipids, apoE4 appears to use an unknown pathway for up-regulating neuronal adhesion and neurite outgrowth. Our results indicate that apoE4 is better than LN as a substrate for primary cultures of CNS neurons and should be considered in the design of tissue engineered CNS.

  4. Long-lasting changes in DNA methylation following short-term hypoxic exposure in primary hippocampal neuronal cultures.

    Directory of Open Access Journals (Sweden)

    Iain Hartley

    Full Text Available While the effects of hypoxia on gene expression have been investigated in the CNS to some extent, we currently do not know what role epigenetics plays in the transcription of many genes during such hypoxic stress. To start understanding the role of epigenetic changes during hypoxia, we investigated the long-term effect of hypoxia on gene expression and DNA methylation in hippocampal neuronal cells. Primary murine hippocampal neuronal cells were cultured for 7 days. Hypoxic stress of 1% O2, 5% CO2 for 24 hours was applied on Day 3, conditions we found to maximize cellular hypoxic stress response without inducing cell death. Cells were returned to normoxia for 4 days following the period of hypoxic stress. On Day 7, Methyl-Sensitive Cut Counting (MSCC was used to identify a genome-wide methylation profile of the hippocampal cell lines to assess methylation changes resulting from hypoxia. RNA-Seq was also done on Day 7 to analyze changes in gene transcription. Phenotypic analysis showed that neuronal processes were significantly shorter after 1 day of hypoxia, but there was a catch-up growth of these processes after return to normoxia. Transcriptome profiling using RNA-Seq revealed 369 differentially expressed genes with 225 being upregulated, many of which form networks shown to affect CNS development and function. Importantly, the expression level of 59 genes could be correlated to the changes in DNA methylation in their promoter regions. CpG islands, in particular, had a strong tendency to remain hypomethylated long after hypoxic stress was removed. From this study, we conclude that short-term, sub-lethal hypoxia results in long-lasting changes to genome wide DNA methylation status and that some of these changes can be highly correlated with transcriptional modulation in a number of genes involved in functional pathways that have been previously implicated in neural growth and development.

  5. [Bacteriocidal activity of Streptomyces cultures].

    Science.gov (United States)

    Polishchuk, L V; Bambura, O I; Luk'ianchuk, V V

    2012-01-01

    Bacteriocidal activity of metabolites synthesized by 17 plasmid-containing cultures of Streptomyces has been studied. These cultures were isolated from soils of Ukraine with different anthropogenic contamination. The cultures, in their majority (85.3%), synthesized bioactive metabolites, which suppressed growth of microorganisms of different taxonomical groups, pathogenic for people, animals or plants. None of 17 Streptomyces cultures was able to suppress growth of yeasts or Escherichia coli. All 17 investigated cultures of Streptomyces were polyresistant to antibiotics, which were used in medicine and veterinary: makrolide, aminoglycoside, beta-lactam and other groups. Resistance of 8 cultures to the antibiotic thiostrepton, which was widely used in some branches of science, was found. PMID:23088099

  6. Hippocampal electrical activity of adult rabbits during moderate passive hyperventilation

    International Nuclear Information System (INIS)

    The effects of a moderate passive hyperventilation (HV) were studied in immobilized un-anesthetized rabbits. Hypocapnia (PCO2 = 23.3 ± 2.8 mm Hg) and alkalosis (pH = 7.54 ± 0.07) were measured on arterial samples. PO2 remained stable. The following results were obtained. From the onset of HV, the mean discharge rate (F) of the pyramidal cells (CA1) was modified. Several types of cellular behaviours were defined according to whether F decreased (51 pc of the neurons), increased (39 pc) or remained stable (6 pc). The most marked effect was observed 15 min after HV onset when 87 pc of cells showed a discharge rate lower than in controls. Whatever F variations, the temporal organization of the action potentials remained unchanged in 71 pc of cases. The evoked response resulting from the stimulation of the commissural inputs corresponded with the activity of GABA inhibitory neurons (basket cells). The response threshold, amplitude and latency were not modified by HV. Only the facilitation process resulting from paired pulses was modified in its late stage. These results as well as those concerning unit activity do not support various assumption such as trouble of the neuronal energetic metabolism due to hypoxia, modification of ionic exchanges (Na+, K+, Ca++), or variations of neurotransmitter concentrations (especially GABA). The effects observed could be ascribed to modifications of neuronal membrane resting potential resulting from direct action of CO2 and alkalosis. (author)

  7. Role of hippocampal activity-induced transcription in memory consolidation.

    Science.gov (United States)

    Eagle, Andrew L; Gajewski, Paula A; Robison, Alfred J

    2016-08-01

    Experience-dependent changes in the strength of connections between neurons in the hippocampus (HPC) are critical for normal learning and memory consolidation, and disruption of this process drives a variety of neurological and psychiatric diseases. Proper HPC function relies upon discrete changes in gene expression driven by transcription factors (TFs) induced by neuronal activity. Here, we describe the induction and function of many of the most well-studied HPC TFs, including cyclic-AMP response element binding protein, serum-response factor, AP-1, and others, and describe their role in the learning process. We also discuss the known target genes of many of these TFs and the purported mechanisms by which they regulate long-term changes in HPC synaptic strength. Moreover, we propose that future research in this field will depend upon unbiased identification of additional gene targets for these activity-dependent TFs and subsequent meta-analyses that identify common genes or pathways regulated by multiple TFs in the HPC during learning or disease. PMID:27180338

  8. Cell surface area regulation in neurons in hippocampal slice cultures is resistant to oxygen-glucose deprivation

    Directory of Open Access Journals (Sweden)

    Natalya Shulyakova

    2010-09-01

    Full Text Available Natalya Shulyakova1,2, Jamie Fong2, Diana Diec2, Adrian Nahirny1,2, Linda R Mills1,21Department of Physiology, University of Toronto, Toronto, ON, Canada, M5T 2S8; 2Toronto Western Hospital Research Institute, University Health Network, 11-430, 399 Bathurst St, Toronto, ON, Canada, M5T 2S8Background: Neurons swell in response to a variety of insults. The capacity to recover, ie, to shrink, is critical for neuronal function and survival. Studies on dissociated neurons have shown that during swelling and shrinking, neurons reorganize their plasma membrane; as neurons swell, in response to hypo-osmotic media, the bilayer area increases. Upon restoration of normo-osmotic media, neurons shrink, forming transient invaginations of the plasma membrane known as vacuole-like dilations (VLDs, to accommodate the decrease in the bilayer.Methods: Here we used confocal microscopy to monitor neuronal swelling and shrinking in the three-dimensional (3D environment of post-natal rat hippocampal slice cultures. To label neurons, we used biolistic transfection, to introduce enhanced green fluorescent protein (eGFP targeted to the cytoplasm; and a membrane targeted GFP (lckGFP, targeted to the plasma membrane.Results: Neurons in slice cultures swelled and shrank in response to hypo-osmotic to normo-osmotic media changes. Oxygen-glucose deprivation (OGD caused sustained neuronal swelling; after reperfusion, some neurons recovered but in others, VLD recovery was stalled. OGD did not impair neuronal capacity to recover from a subsequent osmotic challenge.Conclusion: These results suggest cell surface area regulation (SAR is an intrinsic property of neurons, and that neuronal capacity for SAR may play an important role in the brain’s response to ischemic insults.Keywords: neurons, swelling, ischemia, cell surface area, hippocampal slice culture

  9. Lead Can Inhibit NMDA-, K+-, QA/KA-Induced Increases in Intracellular Free Ca2+ in Cultured Rat Hippocampal Neurons

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To examine the effects of Pb2+ on N-methyl-D-aspartate (NMDA)-, K+- and quisqualate(QA)/kainite(KA)-induced increases in intracellular free calcium concentration ([Ca2+]i) in cultured fetal rat hippocampal neurons in order to explain the cognitive and learning deficits produced by this heavy metal. Methods Laser scanning confocal microscopy was used. Results The results clearly demonstrated that adding Pb2+ before or after NMDA/glycine stimulation selectively inhibited the stimulated increases in [Ca2+]i in a concentration-dependent manner. In contrast, Pb2+ treatment did not markedly affect increases in [Ca2+]i induced by an admixture of QA and KA. The minimal inhibitory effect of Pb2+ occurred at 1 μ mol/L, and more than seventy percent abolition of the NMDA-stimulated increase in [Ca2+]iwas observed at 100 μmol/L Pb2+. Evaluation of pb2+-induced increase in [Ca2+]i response to elevating extracellular concentrations of NMDA, glycine or calcium revealed that Pb2+ was a noncompetitive antagonist of both NMDA and glycine, and a competitive antagonist of Ca2+ at NMDA receptor channels. In addition, Pb2+ inhibited depolarization-evoked increases in [Ca2+]i mediated by K+ stimulation (30 μmol/L), indicating that Pb2+ also depressed the voltage-dependent calcium channels. Also, the results showed that Pb2+ appeared to be able to elevate the resting levels of [Ca2+]i in cultured neurons, implying a reason for pb2+-enhanced spontaneous release of several neurotransmitters reported in several previous studies. Conclusion Lead can inhibit NMDA-, K+-, QA/KA-inducod increases in intracellular [Ca2+]i in cultured hippocampal neurons.

  10. Neuroprotective effects of the AMPA antagonist PNQX in oxygen-glucose deprivation in mouse hippocampal slice cultures and global cerebral ischemia in gerbils

    DEFF Research Database (Denmark)

    Montero, Maria; Nielsen, Marianne; Rønn, Lars Christian B;

    2007-01-01

    PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective AMPA antagonist with demonstrated neuroprotective effects in focal ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to oxygen and glucose deprivation (OGD) and in tr...

  11. The developmental expression of fluorescent proteins in organotypic hippocampal slice cultures from transgenic mice and its use in the determination of excitotoxic neurodegeneration

    DEFF Research Database (Denmark)

    Noraberg, Jens; Jensen, Carsten V; Bonde, Christian;

    2007-01-01

    changes, as well as the opportunity to monitor reversible changes or long-term effects in the event of minor damage. As a first step, we present: a) the developmental expression in organotypic hippocampal brain slice cultures of transgenic fluorescent proteins, useful for the visualisation of neuronal...

  12. The Gαo Activator Mastoparan-7 Promotes Dendritic Spine Formation in Hippocampal Neurons

    Science.gov (United States)

    Ramírez, Valerie T.; Ramos-Fernández, Eva; Inestrosa, Nibaldo C.

    2016-01-01

    Mastoparan-7 (Mas-7), an analogue of the peptide mastoparan, which is derived from wasp venom, is a direct activator of Pertussis toxin- (PTX-) sensitive G proteins. Mas-7 produces several biological effects in different cell types; however, little is known about how Mas-7 influences mature hippocampal neurons. We examined the specific role of Mas-7 in the development of dendritic spines, the sites of excitatory synaptic contact that are crucial for synaptic plasticity. We report here that exposure of hippocampal neurons to a low dose of Mas-7 increases dendritic spine density and spine head width in a time-dependent manner. Additionally, Mas-7 enhances postsynaptic density protein-95 (PSD-95) clustering in neurites and activates Gαo signaling, increasing the intracellular Ca2+ concentration. To define the role of signaling intermediates, we measured the levels of phosphorylated protein kinase C (PKC), c-Jun N-terminal kinase (JNK), and calcium-calmodulin dependent protein kinase IIα (CaMKIIα) after Mas-7 treatment and determined that CaMKII activation is necessary for the Mas-7-dependent increase in dendritic spine density. Our results demonstrate a critical role for Gαo subunit signaling in the regulation of synapse formation. PMID:26881110

  13. The Gαo Activator Mastoparan-7 Promotes Dendritic Spine Formation in Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Valerie T. Ramírez

    2016-01-01

    Full Text Available Mastoparan-7 (Mas-7, an analogue of the peptide mastoparan, which is derived from wasp venom, is a direct activator of Pertussis toxin- (PTX- sensitive G proteins. Mas-7 produces several biological effects in different cell types; however, little is known about how Mas-7 influences mature hippocampal neurons. We examined the specific role of Mas-7 in the development of dendritic spines, the sites of excitatory synaptic contact that are crucial for synaptic plasticity. We report here that exposure of hippocampal neurons to a low dose of Mas-7 increases dendritic spine density and spine head width in a time-dependent manner. Additionally, Mas-7 enhances postsynaptic density protein-95 (PSD-95 clustering in neurites and activates Gαo signaling, increasing the intracellular Ca2+ concentration. To define the role of signaling intermediates, we measured the levels of phosphorylated protein kinase C (PKC, c-Jun N-terminal kinase (JNK, and calcium-calmodulin dependent protein kinase IIα (CaMKIIα after Mas-7 treatment and determined that CaMKII activation is necessary for the Mas-7-dependent increase in dendritic spine density. Our results demonstrate a critical role for Gαo subunit signaling in the regulation of synapse formation.

  14. Influence of Electroacupuncture on COX Activity of Hippocampal Mitochondria in Senescence- accelerated Mouse Prone 8 Mice

    Institute of Scientific and Technical Information of China (English)

    Peng Jing; Zeng Fang; He Yu-heng; Tang Yong; Yin Hai-yan; Yu Shu-guang

    2014-01-01

    Objective: To observe the effect of electroacupuncture (EA) on cytochrome c oxidase (COX)activity of hippocampal mitochondria in senescence-accelerated mouse prone 8 (SAMP8) mice, and to explore the EA mechanism on Alzheimer disease (AD) in improving energy metabolic disorder. Methods: Twelve SAMP8 mice were randomly divided into a model group and an EA group, with six in each group. Six senescence-accelerated mouse resistance 1 (SAMR1) mice were prepared as blank group. Mice in the EA group received EA on Baihui (GV 20) and Yongquan (KI 1), once a day for 7 d as a course, altogether 3 courses with one day intervalbetween two courses. Mice in the model group and the blank group were manipulated and fixed as those in the EA group. After interventions, Morris water maze was employed to test spatial learning and memory ability to evaluate EA effect; spectrophotometry was used to detect the activity of hippocampal mitochondria COX. Results: Compared with the blank group, mean escape latenciesof the EA group and model group were prolonged significantly in Morris water maze tests (P Conclusion: It’s plausible that EA improves AD learning and memory ability by increasing mitochondria COX activity, protecting the structure and function, and improving energy metabolism.

  15. Excitatory effects of parvalbumin-expressing interneurons maintain hippocampal epileptiform activity via synchronous afterdischarges.

    Science.gov (United States)

    Ellender, Tommas J; Raimondo, Joseph V; Irkle, Agnese; Lamsa, Karri P; Akerman, Colin J

    2014-11-12

    Epileptic seizures are characterized by periods of hypersynchronous, hyperexcitability within brain networks. Most seizures involve two stages: an initial tonic phase, followed by a longer clonic phase that is characterized by rhythmic bouts of synchronized network activity called afterdischarges (ADs). Here we investigate the cellular and network mechanisms underlying hippocampal ADs in an effort to understand how they maintain seizure activity. Using in vitro hippocampal slice models from rats and mice, we performed electrophysiological recordings from CA3 pyramidal neurons to monitor network activity and changes in GABAergic signaling during epileptiform activity. First, we show that the highest synchrony occurs during clonic ADs, consistent with the idea that specific circuit dynamics underlie this phase of the epileptiform activity. We then show that ADs require intact GABAergic synaptic transmission, which becomes excitatory as a result of a transient collapse in the chloride (Cl(-)) reversal potential. The depolarizing effects of GABA are strongest at the soma of pyramidal neurons, which implicates somatic-targeting interneurons in AD activity. To test this, we used optogenetic techniques to selectively control the activity of somatic-targeting parvalbumin-expressing (PV(+)) interneurons. Channelrhodopsin-2-mediated activation of PV(+) interneurons during the clonic phase generated excitatory GABAergic responses in pyramidal neurons, which were sufficient to elicit and entrain synchronous AD activity across the network. Finally, archaerhodopsin-mediated selective silencing of PV(+) interneurons reduced the occurrence of ADs during the clonic phase. Therefore, we propose that activity-dependent Cl(-) accumulation subverts the actions of PV(+) interneurons to perpetuate rather than terminate pathological network hyperexcitability during the clonic phase of seizures. PMID:25392490

  16. Converging action of alcohol consumption and cannabinoid receptor activation on adult hippocampal neurogenesis.

    Science.gov (United States)

    Alén, Francisco; Mouret, Aurélie; Viveros, Maria-Paz; Llorente, Ricardo; Lepousez, Gabriel; Lledo, Pierre-Marie; López-Moreno, José Antonio

    2010-03-01

    Alcoholism is characterized by successive periods of abstinence and relapse, resulting from long-lasting changes in various circuits of the central nervous system. Accumulating evidence points to the endocannabinoid system as one of the most relevant biochemical systems mediating alcohol addiction. The endocannabinoid system regulates adult neurogenesis, a form of long-lasting adult plasticity that occurs in a few areas of the brain, including the dentate gyrus. Because exposure to psychotropic drugs regulates adult neurogenesis, it is possible that neurogenesis might be implicated in the pathophysiology, and hence treatment, of neurobiological illnesses related to drugs of abuse. Here, we investigated the sensitivity of adult hippocampal neurogenesis to alcohol and the cannabinoid receptor agonist WIN 55,212-2 (WIN). Specifically, we analysed the potential link between alcohol relapse, cannabinoid receptor activation, and adult neurogenesis. Adult rats were exposed to subchronic alcohol binge intoxication and received the cannabinoid receptor agonist WIN. Another group of rats were subjected to an alcohol operant self-administration task. Half of these latter animals had continuous access to alcohol, while the other half were subjected to alcohol deprivation, with or without WIN administration. WIN treatment, when administered during alcohol deprivation, resulted in the greatest increase in alcohol consumption during relapse. Together, forced alcohol binge intoxication and WIN administration dramatically reduced hippocampal neurogenesis. Furthermore, adult neurogenesis inversely correlated with voluntary consumption of alcohol. These findings suggest that adult hippocampal neurogenesis is a key factor involved in drug abuse and that it may provide a new strategy for the treatment of alcohol addiction and dependence.

  17. Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD.

    Science.gov (United States)

    Hayes, Jasmeet Pannu; LaBar, Kevin S; McCarthy, Gregory; Selgrade, Elizabeth; Nasser, Jessica; Dolcos, Florin; Morey, Rajendra A

    2011-05-01

    Neurobiological models of posttraumatic stress disorder (PTSD) suggest that altered activity in the medial temporal lobes (MTL) during encoding of traumatic memories contribute to the development and maintenance of the disorder. However, there is little direct evidence in the PTSD literature to support these models. The goal of the present study was to examine MTL activity during trauma encoding in combat veterans using the subsequent memory paradigm. Fifteen combat veterans diagnosed with PTSD and 14 trauma-exposed control participants viewed trauma-related and neutral pictures while undergoing event-related fMRI. Participants returned one week after scanning for a recognition memory test. Region-of-interest (ROI) and voxel-wise whole brain analyses were conducted to examine the neural correlates of successful memory encoding. Patients with PTSD showed greater false alarm rates for novel lures than the trauma-exposed control group, suggesting reliance on gist-based representations in lieu of encoding contextual details. Imaging analyses revealed reduced activity in the amygdala and hippocampus in PTSD patients during successful encoding of trauma-related stimuli. Reduction in left hippocampal activity was associated with high arousal symptoms on the Clinician-Administered PTSD Scale (CAPS). The behavioral false alarm rate for traumatic stimuli co-varied with activity in the bilateral precuneus. These results support neurobiological theories positing reduced hippocampal activity under conditions of high stress and arousal. Reduction in MTL activity for successfully encoded stimuli and increased precuneus activity may underlie reduced stimulus-specific encoding and greater gist memory in patients with PTSD, leading to maintenance of the disorder. PMID:21047644

  18. Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

    Directory of Open Access Journals (Sweden)

    Elena eCid

    2014-04-01

    Full Text Available Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e. the multiple-hit hypothesis. However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1; including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

  19. Hippocampal expression of apoptotic protease activating factor-1 following diffuse axonal injury under mild hypothermia

    Institute of Scientific and Technical Information of China (English)

    Peng Yang; Limin Zhang; Yunhe Zhang; Xifeng Zou; Qunxi Li; Yun Li; Jun Zhu; Jianmin Li; Aijun Fu; Qingjun Liu; Tong Chen; Zelin Sun; Zhiyong Zhang

    2011-01-01

    The influence of mild hypothermia on neural cell apoptosis remains poorly understood. Therefore, the present study established rat models of diffuse axonal injury (DAI) at 33 °C. Morris water maze results demonstrated significantly better learning and memory functions in DAI rats with hypothermia compared with DAI rats with normothermia. Expression of apoptotic protease activating factor-1 in the hippocampal CA1 region was significantly lower in the DAI hypothermia group compared with the DAI normothermia group. Expression of apoptotic protease activating factor-1 positively correlated with latency, but negatively correlated with platform location times and time of swimming in the quadrant area. Results suggested that post-traumatic mild hypothermia in a rat model of DAI could provide cerebral protection by attenuating expression of apoptotic protease activating factor-1.

  20. Prenatal immune activation alters hippocampal place cell firing characteristics in adult animals.

    Science.gov (United States)

    Wolff, Amy R; Bilkey, David K

    2015-08-01

    Prenatal maternal immune activation (MIA) is a risk factor for several developmental neuropsychiatric disorders, including autism, bipolar disorder and schizophrenia. Adults with these disorders display alterations in memory function that may result from changes in the structure and function of the hippocampus. In the present study we use an animal model to investigate the effect that a transient prenatal maternal immune activation episode has on the spatially-modulated firing activity of hippocampal neurons in adult animals. MIA was induced in pregnant rat dams with a single injection of the synthetic cytokine inducer polyinosinic:polycytidylic acid (poly I:C) on gestational day 15. Control dams were given a saline equivalent. Firing activity and local field potentials (LFPs) were recorded from the CA1 region of the adult male offspring of these dams as they moved freely in an open arena. Most neurons displayed characteristic spatially-modulated 'place cell' firing activity and while there was no between-group difference in mean firing rate between groups, place cells had smaller place fields in MIA-exposed animals when compared to control-group cells. Cells recorded in MIA-group animals also displayed an altered firing-phase synchrony relationship to simultaneously recorded LFPs. When the floor of the arena was rotated, the place fields of MIA-group cells were more likely to shift in the same direction as the floor rotation, suggesting that local cues may have been more salient for these animals. In contrast, place fields in control group cells were more likely to shift firing position to novel spatial locations suggesting an altered response to contextual cues. These findings show that a single MIA intervention is sufficient to change several important characteristics of hippocampal place cell activity in adult offspring. These changes could contribute to the memory dysfunction that is associated with MIA, by altering the encoding of spatial context and by

  1. Dopamine receptor activation reorganizes neuronal ensembles during hippocampal sharp waves in vitro.

    Directory of Open Access Journals (Sweden)

    Takeyuki Miyawaki

    Full Text Available Hippocampal sharp wave (SW/ripple complexes are thought to contribute to memory consolidation. Previous studies suggest that behavioral rewards facilitate SW occurrence in vivo. However, little is known about the precise mechanism underlying this enhancement. Here, we examined the effect of dopaminergic neuromodulation on spontaneously occurring SWs in acute hippocampal slices. Local field potentials were recorded from the CA1 region. A brief (1 min treatment with dopamine led to a persistent increase in the event frequency and the magnitude of SWs. This effect lasted at least for our recording period of 45 min and did not occur in the presence of a dopamine D1/D5 receptor antagonist. Functional multineuron calcium imaging revealed that dopamine-induced SW augmentation was associated with an enriched repertoire of the firing patterns in SW events, whereas the overall tendency of individual neurons to participate in SWs and the mean number of cells participating in a single SW were maintained. Therefore, dopaminergic activation is likely to reorganize cell assemblies during SWs.

  2. 3-Nitropropionic acid neurotoxicity in hippocampal slice cultures: developmental and regional vulnerability and dependency on glucose

    DEFF Research Database (Denmark)

    Noer, Helle; Kristensen, Bjarne W; Noraberg, Jens;

    2002-01-01

    : CA1 > CA3 > fascia dentata. In low glucose much lower concentrations of 3-NP (25 microM) triggered neurotoxicity. One-week-old cultures were less susceptible to 3-NP toxicity than 3-week-old cultures, but the dentate granule cells were relatively more affected in the immature cultures. We found...

  3. Profiles of hippocampal neuron activity during auditory discrimination cognition in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    GAO Jie; LUO Jun; XIONG Ying; YANG Ce; WANG Yong-tang; SUI Jian-feng

    2007-01-01

    Objective: To clarify the firing characteristics of the hippocampal pyramidal cells and interneurons in the auditory discrimination cognition. Methods: Thirteen guinea pigs were studied by the paired (active cognition group, n=10) or unpaired (passive cognition group, n=3) training with 1 kHz (CS+)and 500 Hz tones (CS-) and the air puff (US) applied 250 ms after the CS+ onset. Results: In active group, 32 pyramidal cells showed exciting response to the CS+ tone, 16 cells inhibited response and 4 cells revealed no response to the high frequency tone and18 interneurons almost unchanged. In passive group, the pyramidal cells responded to the tone casually and 10 out of the 13 interneurons remained invariably. Conclusion: The result suggests that the pyramidal cells play a major role in coding auditory information by the networks, and the interneuons may modulate it via forward and feedback.

  4. Neural stem cell activation and glial proliferation in the hippocampal CA3 region of posttraumatic epileptic rats

    Institute of Scientific and Technical Information of China (English)

    Yuanxiang Lin; Kun Lin; Dezhi Kang; Feng Wang

    2011-01-01

    The present study observed the dynamic expression of CD133, nuclear factor-κB and glial fibrillary acidic protein in the hippocampal CA3 area of the experimental posttraumatic epilepsy rats to investigate whether gliosis occurs after posttraumatic epilepsy. CD133 and nuclear factor-κB expression was increased at 1 day after posttraumatic epilepsy, peaked at 7 days, and gradually decreased up to 14 days, as seen by double-immunohistochemical staining. Glial fibrillary acidic protein/nuclear factor-κB double-labeled cells increased with time and peaked at 14 days after posttraumatic epilepsy. Results show that activation of hippocampal neural stem cells and glial proliferation after posttraumatic epilepsy-induced oxidative stress increases hippocampal glial cell density.

  5. CB1 receptor deficiency decreases wheel-running activity: consequences on emotional behaviours and hippocampal neurogenesis.

    Science.gov (United States)

    Dubreucq, Sarah; Koehl, Muriel; Abrous, Djoher N; Marsicano, Giovanni; Chaouloff, Francis

    2010-07-01

    Chronic voluntary wheel-running activity has been reported to hypersensitise central CB1 receptors in mice. On the other hand, pharmacological findings suggest that the CB1 receptor could be involved in wheel-running behaviour and in running-induced neurogenesis in the hippocampus. We analysed wheel-running behaviour for 6 weeks and measured its consequences on hippocampal neurogenesis in CB1 knockout (CB1(-/-)) animals, compared to wild-type (CB1(+/+)) littermates. Because wheel running has been shown to affect locomotor reactivity in novel environments, memory for aversive events and depression-like behaviours, we also assessed these behaviours in control and running CB1(+/+) and CB1(-/-) mice. When compared with running CB1(+/+) mice, the distance covered weekly by CB1(-/-) mice was decreased by 30-40%, an observation accounted for by decreased time spent and maximal velocity on the wheels. Analyses of running distances with respect to the light/dark cycle revealed that mutant covered less distance throughout both the inactive and the active phases of that cycle. Locomotion in an activity cage, exploration in an open field, and immobility time in the forced swim test proved insensitive to chronic wheel running in either genotype. Wheel running, per se, did not influence the expression and extinction of cued fear memory but counteracted in a time-dependent manner the deficiency of extinction measured in CB1(-/-) mice. Hippocampal neurogenesis, assessed by doublecortin labelling of immature neurons in the dentate gyrus, was lowered by 40% in control CB1(-/-) mice, compared to control CB1(+/+) mice. Although CB1(-/-) mice ran less than their wild-type littermates, the 6-week running protocol increased neurogenesis to similar extents (37-39%) in both genotypes. This study suggests that mouse CB1 receptors control wheel running but not its neurogenic consequences in the hippocampus.

  6. 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.

  7. Slowing of Hippocampal Activity Correlates with Cognitive Decline in Early Onset Alzheimer's Disease. An MEG Study with Virtual Electrodes.

    Science.gov (United States)

    Engels, Marjolein M A; Hillebrand, Arjan; van der Flier, Wiesje M; Stam, Cornelis J; Scheltens, Philip; van Straaten, Elisabeth C W

    2016-01-01

    Pathology in Alzheimer's disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using "virtual MEG electrodes". We used resting-state MEG recordings from 27 early onset AD patients [age 60.6 ± 5.4, 12 females, mini-mental state examination (MMSE) range: 19-28] and 26 cognitively healthy age- and gender-matched controls (age 61.8 ± 5.5, 14 females). Activity was reconstructed using beamformer-based virtual electrodes for 78 cortical regions and 6 hippocampal regions. Group differences in peak frequency and relative power in six frequency bands were identified using permutation testing. For the patients, spearman correlations between the MMSE scores and peak frequency or relative power were calculated. Moreover, receiver operator characteristic curves were plotted to estimate the diagnostic accuracy. We found a lower hippocampal peak frequency in AD compared to controls, which, in the patients, correlated positively with MMSE [r(25) = 0.61; p discriminator between AD and controls (sensitivity 82%; specificity 81%). Using beamformer-based virtual electrodes, we were able to detect hippocampal activity in AD. In AD, this hippocampal activity is slowed, and correlates better with cognition than the (slowed) activity in cortical areas. On the other hand, the average cortical relative power in the theta band was shown to be the best diagnostic discriminator. We postulate that this novel approach using virtual electrodes can be used in future research to quantify functional interactions between the hippocampi and cortical areas. PMID:27242496

  8. Prenatal alcohol exposure alters synaptic activity of adult hippocampal dentate granule cells under conditions of enriched environment.

    Science.gov (United States)

    Kajimoto, Kenta; Valenzuela, C Fernando; Allan, Andrea M; Ge, Shaoyu; Gu, Yan; Cunningham, Lee Anna

    2016-08-01

    Prenatal alcohol exposure (PAE) results in fetal alcohol spectrum disorder (FASD), which is characterized by a wide range of cognitive and behavioral deficits that may be linked to impaired hippocampal function and adult neurogenesis. Preclinical studies in mouse models of FASD indicate that PAE markedly attenuates enrichment-mediated increases in the number of adult-generated hippocampal dentate granule cells (aDGCs), but whether synaptic activity is also affected has not been studied. Here, we utilized retroviral birth-dating coupled with whole cell patch electrophysiological recordings to assess the effects of PAE on enrichment-mediated changes in excitatory and inhibitory synaptic activity as a function of DGC age. We found that exposure to an enriched environment (EE) had no effect on baseline synaptic activity of 4- or 8-week-old aDGCs from control mice, but significantly enhanced the excitatory/inhibitory ratio of synaptic activity in 8-week-old aDGCs from PAE mice. In contrast, exposure to EE significantly enhanced the excitatory/inhibitory ratio of synaptic activity in older pre-existing DGCs situated in the outer dentate granule cell layer (i.e., those generated during embryonic development; dDGCs) in control mice, an effect that was blunted in PAE mice. These findings indicate distinct electrophysiological responses of hippocampal DGCs to behavioral challenge based on cellular ontogenetic age, and suggest that PAE disrupts EE-mediated changes in overall hippocampal network activity. These findings may have implications for future therapeutic targeting of hippocampal dentate circuitry in clinical FASD. © 2016 Wiley Periodicals, Inc. PMID:27009742

  9. Cultural Isolation and Cultural Integration: A Communicative Language Activity.

    Science.gov (United States)

    Courtney, John

    2002-01-01

    Provides a theoretical grounding to an activity that follows a communicative language teaching approach to teaching English as a Second or Foreign Language. The activity, cultural isolation and cultural integration, motivates learners to relate their experiences and feelings in regard to diverse cultures. (Author/VWL)

  10. Release probability of hippocampal glutamatergic terminals scales with the size of the active zone.

    Science.gov (United States)

    Holderith, Noemi; Lorincz, Andrea; Katona, Gergely; Rózsa, Balázs; Kulik, Akos; Watanabe, Masahiko; Nusser, Zoltan

    2012-06-10

    Cortical synapses have structural, molecular and functional heterogeneity; our knowledge regarding the relationship between their ultrastructural and functional parameters is still fragmented. Here we asked how the neurotransmitter release probability and presynaptic [Ca(2+)] transients relate to the ultrastructure of rat hippocampal glutamatergic axon terminals. Two-photon Ca(2+) imaging-derived optical quantal analysis and correlated electron microscopic reconstructions revealed a tight correlation between the release probability and the active-zone area. Peak amplitude of [Ca(2+)] transients in single boutons also positively correlated with the active-zone area. Freeze-fracture immunogold labeling revealed that the voltage-gated calcium channel subunit Cav2.1 and the presynaptic protein Rim1/2 are confined to the active zone and their numbers scale linearly with the active-zone area. Gold particles labeling Cav2.1 were nonrandomly distributed in the active zones. Our results demonstrate that the numbers of several active-zone proteins, including presynaptic calcium channels, as well as the number of docked vesicles and the release probability, scale linearly with the active-zone area.

  11. The alterations in biochemical signaling of hippocampal network activity in the autism brain The alterations in biochemical signaling of hippocampal network activity in the autism brain The alterations in biochemical signaling of hippocampal network activity in the autism brain

    Institute of Scientific and Technical Information of China (English)

    田允; 黄继云; 王锐; 陶蓉蓉; 卢应梅; 廖美华; 陆楠楠; 李静; 芦博; 韩峰

    2012-01-01

    Autism is a highly heritable neurodevelopmental condition characterized by impaired social interaction and communication. However, the role of synaptic dysfunction during development of autism remains unclear. In the present study, we address the alterations of biochemical signaling in hippocampal network following induction of the autism in experimental animals. Here, the an- imal disease model and DNA array being used to investigate the differences in transcriptome or- ganization between autistic and normal brain by gene co--expression network analysis.

  12. Hippocampal EEG and motor activity in the cat: The role of eye movements and body acceleration

    NARCIS (Netherlands)

    Kamp, A.; Arnolds, D.E.A.T.; Lopes da Silva, F.H.; Boeijinga, P.; Aitink, W.

    1984-01-01

    In cat the relation between various behaviours and the spectral properties of the hippocampal EEG was investigated. Both EEG and behaviour were quantified and results were evaluated statistically. Significant relationships were found between the properties of the hippocampal EEG and motor acts (walk

  13. Sequential expression of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor in rat hippocampal neurons after fluid percussion injury

    Institute of Scientific and Technical Information of China (English)

    Zhiqiang Li; Qingming Shu; Lingzhi Li; Maolin Ge; Yongliang Zhang

    2014-01-01

    Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. However, little is known about the correlation of these three factors and brain neuronal injury. In this study, primary cultured rat hippocampal neurons were subjected to fluid percussion injury according to Scott’s method, with some modifications. RT-PCR and semi-quantitative immunocytochemical staining was used to measure the expression levels of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. Our results found that cycloox-ygenase-2 expression were firstly increased post-injury, and then decreased. Both mRNA and protein expression levels reached peaks at 8 and 12 hours post-injury, respectively. Similar sequential changes in glutamate receptor 2 were observed, with highest levels mRNA and pro-tein expression at 8 and 12 hours post-injury respectively. On the contrary, the expressions of platelet activating factor receptor were firstly decreased post-injury, and then increased. Both mRNA and protein expression levels reached the lowest levels at 8 and 12 hours post-injury, respectively. Totally, our findings suggest that these three factors are involved in occurrence and development of hippocampal neuronal injury.

  14. Differential induction of heme oxygenase and other stress proteins in cultured hippocampal astrocytes and neurons by inorganic lead

    International Nuclear Information System (INIS)

    We examined the effects of exposure to inorganic lead (Pb2+) on the induction of stress proteins in cultured hippocampal neurons and astrocytes, with particular emphasis on the induction of heme oxygenase-1 (HO-1). In radiolabeled neuronal cultures, Pb2+ exposure had no significant effect on the synthesis of any protein at any concentration (up to 250 μM) or duration of exposure (up to 4 days). In radiolabeled astrocyte cultures, however, Pb2+ exposure (100 nM to 100 μM; 1-4 days) increased synthesis of proteins with approximate molecular weights of 23, 32, 45, 57, 72, and 90 kDa. Immunoblot experiments showed that Pb2+ exposure (100 nM to 10 μM, 1-14 days) induces HO-1 synthesis in astrocytes, but not in neurons; this is probably the 32-kDa protein. The other heme oxygenase isoform, HO-2, is present in both neurons and astrocytes, but is not inducible by Pb2+ at concentrations up to 100 μM. HO-1 can be induced by a variety of stimuli. We found that HO-1 induction in astrocytes is increased by combined exposure to Pb2+ and many other stresses, including heat, nitric oxide, H2O2, and superoxide. One of the stimuli that may induce HO-1 is oxidative stress. Lead exposure causes oxidative stress in many cell types, including astrocytes. Induction of HO-1 by Pb2+ is reduced by the hydroxyl radical scavengers dimethylthiourea (DMTU) and mannitol, but not by inhibitors of calmodulin, calmodulin-dependent protein kinases, protein kinase C, or extracellular signal-regulated kinases (ERK). Therefore, we conclude that oxidative stress is an important mechanism by which Pb2+ induces HO-1 synthesis in astrocytes

  15. Glycolysis and oxidative phosphorylation in neurons and astrocytes during network activity in hippocampal slices.

    Science.gov (United States)

    Ivanov, Anton I; Malkov, Anton E; Waseem, Tatsiana; Mukhtarov, Marat; Buldakova, Svetlana; Gubkina, Olena; Zilberter, Misha; Zilberter, Yuri

    2014-03-01

    Network activation triggers a significant energy metabolism increase in both neurons and astrocytes. Questions of the primary neuronal energy substrate (e.g., glucose vs. lactate) as well as the relative contributions of glycolysis and oxidative phosphorylation and their cellular origin (neurons vs. astrocytes) are still a matter of debates. Using simultaneous measurements of electrophysiological and metabolic parameters during synaptic stimulation in hippocampal slices from mature mice, we show that neurons and astrocytes use both glycolysis and oxidative phosphorylation to meet their energy demands. Supplementation or replacement of glucose in artificial cerebrospinal fluid (ACSF) with pyruvate or lactate strongly modifies parameters related to network activity-triggered energy metabolism. These effects are not induced by changes in ATP content, pH(i), [Ca(2+)](i) or accumulation of reactive oxygen species. Our results suggest that during network activation, a significant fraction of NAD(P)H response (its overshoot phase) corresponds to glycolysis and the changes in cytosolic NAD(P)H and mitochondrial FAD are coupled. Our data do not support the hypothesis of a preferential utilization of astrocyte-released lactate by neurons during network activation in slices--instead, we show that during such activity glucose is an effective energy substrate for both neurons and astrocytes.

  16. Protective Effects of Testosterone on Presynaptic Terminals against Oligomeric β-Amyloid Peptide in Primary Culture of Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Chi-Fai Lau

    2014-01-01

    Full Text Available Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer’s disease (AD, there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by β-amyloid (Aβ, but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβ could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβ also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD.

  17. Reaction of small heat-shock proteins to different kinds of cellular stress in cultured rat hippocampal neurons.

    Science.gov (United States)

    Bartelt-Kirbach, Britta; Golenhofen, Nikola

    2014-01-01

    Upregulation of small heat-shock proteins (sHsps) in response to cellular stress is one mechanism to increase cell viability.We previously described that cultured rat hippocampal neurons express five of the 11 family members but only upregulate two of them (HspB1 and HspB5) at the protein level after heat stress. Since neurons have to cope with many other pathological conditions, we investigated in this study the expression of all five expressed sHsps on mRNA and protein level after sublethal sodium arsenite and oxidative and hyperosmotic stress. Under all three conditions, HspB1, HspB5, HspB6, and HspB8 but not HspB11 were consistently upregulated but showed differences in the time course of upregulation. The increase of sHsps always occurred earlier on mRNA level compared with protein levels. We conclude from our data that these four upregulated sHsps (HspB1, HspB5, HspB6, HspB8) act together in different proportions in the protection of neurons from various stress conditions.

  18. 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.

  19. NF-κB Mediated Regulation of Adult Hippocampal Neurogenesis: Relevance to Mood Disorders and Antidepressant Activity

    Directory of Open Access Journals (Sweden)

    Valeria Bortolotto

    2014-01-01

    Full Text Available Adult hippocampal neurogenesis is a peculiar form of process of neuroplasticity that in recent years has gained great attention for its potential implication in cognition and in emotional behavior in physiological conditions. Moreover, a vast array of experimental studies suggested that adult hippocampal neurogenesis may be altered in various neuropsychiatric disorders, including major depression, where its disregulation may contribute to cognitive impairment and/or emotional aspects associated with those diseases. An intriguing area of interest is the potential influence of drugs on adult neurogenesis. In particular, several psychoactive drugs, including antidepressants, were shown to positively modulate adult hippocampal neurogenesis. Among molecules which could regulate adult hippocampal neurogenesis the NF-κB family of transcription factors has been receiving particular attention from our and other laboratories. Herein we review recent data supporting the involvement of NF-κB signaling pathways in the regulation of adult neurogenesis and in the effects of drugs that are endowed with proneurogenic and antidepressant activity. The potential implications of these findings on our current understanding of the process of adult neurogenesis in physiological and pathological conditions and on the search for novel antidepressants are also discussed.

  20. Aged garlic extract and its components protect cultured rat hippocampal neurons from amyloid β—protein—in—duced neuronal death

    Institute of Scientific and Technical Information of China (English)

    ItoY; KosuY

    2002-01-01

    Aged garlic extract and its components such as S-allyl-L-cysteine (SAC) and sllixin have been shown to possess various biological effects including neurotrophic activity.We characterized the neuronal death induced by amyloid β-protein (Aβ),4-hydroxynoenal (HNE),tunicamycin(TM),and trophic factor-deprivation (TFD),and ivestigated whether these garlic compounds could prevent this in cultured PC12 cells and rat hippocampal neurons.Treatment with SAC protected these cells against Aβ- and TM-induced neuronal death.SAC also attenuated the processing of procaspase-12 induced by Aβ25-35 or TM.In contrast,allixin and its analogue,DHP,afforded no protection against Aβ-induced cell death.SAC afforded no protection against HNE- and TFD-induced cell death,which has been shown to be mediated by caspase-3 dependent pathway.These results suggest that SAC protect against the neuronal cell death that is triggered by ER dysfunction.

  1. Transmembrane Agrin Regulates Dendritic Filopodia and Synapse Formation in Mature Hippocampal Neuron Cultures

    OpenAIRE

    McCroskery, Seumas; Bailey, Allison; Lin, Lin; Daniels, Mathew P.

    2009-01-01

    The transmembrane isoform of agrin (Tm-agrin) is the predominant form expressed in the brain but its putative roles in brain development are not well understood. Recent reports have implicated Tm-agrin in the formation and stabilization of filopodia on neurites of immature central and peripheral neurons in culture. In maturing central neurons, dendritic filopodia are believed to facilitate synapse formation. In the present study we have investigated the role of Tm-agrin in regulation of dendr...

  2. Adaptive enhancement of learning protocol in hippocampal cultured networks grown on multielectrode arrays

    Directory of Open Access Journals (Sweden)

    Alexey ePimashkin

    2013-05-01

    Full Text Available Learning in neuronal networks can be investigated using dissociated cultures on multielectrode arrays supplied with appropriate closed-loop stimulation. It was shown in previous studies that weakly respondent neurons on the electrodes can be trained to increase their evoked spiking rate within predefined time window after the stimulus. Such neurons can be associated with weak synaptic connections in nearby culture network. The stimulation leads to the increase in the connectivity and in the response. However, it was not possible to perform the learning protocol for the neurons on electrodes with relatively strong synaptic inputs and responding at higher rates. We proposed an adaptive closed-loop stimulation protocol capable to achieve learning even for the highly respondent electrodes. It means that the culture network can reorganize appropriately its synaptic connectivity to generate a desired response. We introduced an adaptive reinforcement condition accounted for response variability in control stimulation. It significantly enhanced the learning protocol to many responding electrode independently on its base response level. We also found that learning effect preserved after 4-6 hours after training.

  3. Optical quantal analysis indicates that long-term potentiation at single hippocampal mossy fiber synapses is expressed through increased release probability, recruitment of new release sites, and activation of silent synapses.

    Science.gov (United States)

    Reid, Christopher A; Dixon, Don B; Takahashi, Michiko; Bliss, Tim V P; Fine, Alan

    2004-04-01

    It is generally believed that long-term potentiation (LTP) at hippocampal mossy fiber synapses between dentate granule and CA3 pyramidal cells is expressed through presynaptic mechanisms leading to an increase in quantal content. The source of this increase has remained undefined but could include enhanced probability of transmitter release at existing functional release sites or increases in the number of active release sites. We performed optical quantal analyses of transmission at individual mossy fiber synapses in cultured hippocampal slices, using confocal microscopy and intracellular fluorescent Ca(2+) indicators. Our results indicate that LTP is expressed at functional synapses by both increased probability of transmitter release and recruitment of new release sites, including the activation of previously silent synapses here visualized for the first time.

  4. Ethanol enhances neurosteroidogenesis in hippocampal pyramidal neurons by paradoxical NMDA receptor activation.

    Science.gov (United States)

    Tokuda, Kazuhiro; Izumi, Yukitoshi; Zorumski, Charles F

    2011-07-01

    Using an antibody against 5α-reduced neurosteroids, predominantly allopregnanolone, we found that immunostaining in the CA1 region of rat hippocampal slices was confined to pyramidal neurons. This neurosteroid staining was increased following 15 min administration of 60 mm but not 20 mm ethanol, and the enhancement was blocked by finasteride and dutasteride, selective inhibitors of 5α-reductase, a key enzyme required for allopregnanolone synthesis. Consistent with a prior report indicating that N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation can promote steroid production, we observed that D-2-amino-5-phosphonovalerate (APV), a competitive NMDAR antagonist, blocked the effects of 60 mm ethanol on staining. We previously reported that 60 mm ethanol inhibits the induction of long-term potentiation (LTP), a cellular model for memory formation, in the CA1 region. In the present study, LTP inhibition by 60 mm ethanol was also overcome by both the 5α-reductase inhibitors and by APV. Furthermore, the effects of ethanol on neurosteroid production and LTP were mimicked by a low concentration of NMDA (1 μm), and the ability of NMDA to inhibit LTP and to enhance neurosteroid staining was reversed by finasteride and dutasteride, as well as by APV. These results indicate that ethanol paradoxically enhances GABAergic neurosteroid production by activation of unblocked NMDARs and that acute LTP inhibition by ethanol represents a form of NMDAR-mediated metaplasticity. PMID:21734282

  5. Maternal immune activation differentially impacts mature and adult-born hippocampal neurons in male mice.

    Science.gov (United States)

    Zhang, Zhi; van Praag, Henriette

    2015-03-01

    Schizophrenia is associated with deficits in the hippocampus, a brain area important for learning and memory. The dentate gyrus (DG) of the hippocampus develops both before and after birth. To study the relative contribution of mature and adult-born DG granule cells to disease etiology, we compared both cell populations in a mouse model of psychiatric illness resulting from maternal immune activation. Polyriboinosinic-polyribocytidilic acid (PolyIC, 5mg/kg) or saline was given on gestation day 15 to pregnant female C57Bl/6 mice. Male offspring (n=105), was administered systemic bromodeoxyuridine (BrdU, 50mg/kg) (n=52) or intracerebral retroviral injection into the DG (n=53), to label dividing cells at one month of age. Two months later behavioral tests were performed to evaluate disease phenotype. Immunohistochemistry and whole-cell patch clamping were used to assess morphological and physiological characteristics of DG cells. Three-month-old PolyIC exposed male offspring exhibited deficient pre-pulse inhibition, spatial maze performance and motor coordination, as well as increased depression-like behavior. Histological analysis showed reduced DG volume and parvalbumin positive interneuron number. Both mature and new hippocampal neurons showed modifications in intrinsic properties such as increased input resistance and lower current threshold, and decreased action potential number. Reduced GABAergic inhibitory transmission was observed only in mature DG neurons. Differential impairments in mature DG cells and adult-born new neurons may have implications for behavioral deficits associated with maternal immune activation. PMID:25449671

  6. Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis

    OpenAIRE

    Tokuda, Kazuhiro; O’Dell, Kazuko A.; Izumi, Yukitoshi; Charles F. Zorumski

    2010-01-01

    Benzodiazepines (BDZs) enhance γ-aminobutyric acid-A (GABAA) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors (translocator protein 18kDa, TSPO) and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectivel...

  7. Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures

    OpenAIRE

    Koizumi, Schuichi; Fujishita, Kayoko; Tsuda, Makoto; Shigemoto-Mogami, Yukari; Inoue, Kazuhide

    2003-01-01

    Originally ascribed passive roles in the CNS, astrocytes are now known to have an active role in the regulation of synaptic transmission. Neuronal activity can evoke Ca2+ transients in astrocytes, and Ca2+ transients in astrocytes can evoke changes in neuronal activity. The excitatory neurotransmitter glutamate has been shown to mediate such bidirectional communication between astrocytes and neurons. We demonstrate here that ATP, a primary mediator of intercellular Ca2+ signaling among astroc...

  8. Acetylcholine release in mouse hippocampal CA1 preferentially activates inhibitory-selective interneurons via alpha4 beta2* nicotinic receptor activation

    Directory of Open Access Journals (Sweden)

    L. Andrew Bell

    2015-04-01

    Full Text Available Acetylcholine (ACh release onto nicotinic receptors directly activates subsets of inhibitory interneurons in hippocampal CA1. However, the specific interneurons activated and their effect on the hippocampal network is not completely understood. Therefore, we investigated subsets of hippocampal CA1 interneurons that respond to ACh release through the activation of nicotinic receptors and the potential downstream effects this may have on hippocampal CA1 network function. ACh was optogenetically released in mouse hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated viral mediated transfection. The actions of optogenetically released ACh were assessed on both pyramidal neurons and different interneuron subtypes via whole cell patch clamp methods. Vasoactive intestinal peptide (VIP-expressing interneurons that selectively innervate other interneurons (VIP/IS were excited by ACh through the activation of nicotinic receptors containing alpah4 and beta2 subunits (alpha4 beta2*. ACh release onto VIP/IS was presynaptically inhibited by M2 muscarinic autoreceptors. ACh release produced spontaneous inhibitory postsynaptic current (sIPSC barrages blocked by dihydro-beta-erythroidine in interneurons but not pyramidal neurons. Optogenetic suppression of VIP interneurons did not inhibit these sIPSC barrages suggesting other interneuron-selective interneurons were also excited by 42* nicotinic receptor activation. In contrast, interneurons that innervate pyramidal neuron perisomatic regions were not activated by ACh release onto nicotinic receptors. Therefore, we propose ACh release in CA1 facilitates disinhibition through activation of 42* nicotinic receptors on interneuron-selective interneurons whereas interneurons that innervate pyramidal neurons are less affected by nicotinic receptor activation.

  9. Popular Culture, Cultural Resistance, and Anticonsumption Activism: An Exploration of Culture Jamming as Critical Adult Education

    Science.gov (United States)

    Sandlin, Jennifer A.

    2007-01-01

    This chapter examines popular culture as a site of cultural resistance. Specifically, it explores how "culture jamming," a cultural-resistance activity, can be a form of adult education. It examines adult education and learning as it intersects with both consumerism and popular culture. Focus is placed on a growing social movement of individuals…

  10. Interleukin-1β activates an Src family kinase to stimulate the plasma membrane Ca2+ pump in hippocampal neurons.

    Science.gov (United States)

    Ghosh, Biswarup; Green, Matthew V; Krogh, Kelly A; Thayer, Stanley A

    2016-04-01

    The plasma membrane Ca(2+) ATPase (PMCA) plays a major role in clearing Ca(2+) from the neuronal cytoplasm. The cytoplasmic Ca(2+) clearance rate affects neuronal excitability, synaptic plasticity, and neurotransmission. Here, we examined the modulation of PMCA activity by PTKs in hippocampal neurons. PMCA-mediated Ca(2+) clearance slowed in the presence of pyrazolopyrimidine 2, an inhibitor of Src family kinases (SFKs), and accelerated in the presence of C2-ceramide, an activator of PTKs. Ca(2+) clearance kinetics were attenuated in cells expressing a dominant-negative Src mutant, suggesting that the pump is tonically stimulated by a PTK. Tonic stimulation was reduced in hippocampal neurons expressing short hairpin (sh)RNA directed to mRNA for Yes. shRNA-mediated knockdown of PMCA isoform 1 (PMCA1) removed tonic stimulation of Ca(2+) clearance, indicating that the kinase stimulates PMCA1. IL-1β accelerated Ca(2+) clearance in a manner blocked by an IL-1β receptor antagonist or by an inhibitor of neutral sphingomyelinase, the enzyme that produces ceramide. Thus IL-1β activates an SFK to stimulate the plasma membrane Ca(2+) pump, decreasing the duration of Ca(2+) transients in hippocampal neurons. PMID:26843596

  11. Active dendrites regulate the impact of gliotransmission on rat hippocampal pyramidal neurons.

    Science.gov (United States)

    Ashhad, Sufyan; Narayanan, Rishikesh

    2016-06-01

    An important consequence of gliotransmission, a signaling mechanism that involves glial release of active transmitter molecules, is its manifestation as N-methyl-d-aspartate receptor (NMDAR)-dependent slow inward currents in neurons. However, the intraneuronal spatial dynamics of these events or the role of active dendrites in regulating their amplitude and spatial spread have remained unexplored. Here, we used somatic and/or dendritic recordings from rat hippocampal pyramidal neurons and demonstrate that a majority of NMDAR-dependent spontaneous slow excitatory potentials (SEP) originate at dendritic locations and are significantly attenuated through their propagation across the neuronal arbor. We substantiated the astrocytic origin of SEPs through paired neuron-astrocyte recordings, where we found that specific infusion of inositol trisphosphate (InsP3) into either distal or proximal astrocytes enhanced the amplitude and frequency of neuronal SEPs. Importantly, SEPs recorded after InsP3 infusion into distal astrocytes exhibited significantly slower kinetics compared with those recorded after proximal infusion. Furthermore, using neuron-specific infusion of pharmacological agents and morphologically realistic conductance-based computational models, we demonstrate that dendritically expressed hyperpolarization-activated cyclic-nucleotide-gated (HCN) and transient potassium channels play critical roles in regulating the strength, kinetics, and compartmentalization of neuronal SEPs. Finally, through the application of subtype-specific receptor blockers during paired neuron-astrocyte recordings, we provide evidence that GluN2B- and GluN2D-containing NMDARs predominantly mediate perisomatic and dendritic SEPs, respectively. Our results unveil an important role for active dendrites in regulating the impact of gliotransmission on neurons and suggest astrocytes as a source of dendritic plateau potentials that have been implicated in localized plasticity and place cell

  12. Social observation enhances cross-environment activation of hippocampal place cell patterns

    Science.gov (United States)

    Mou, Xiang; Ji, Daoyun

    2016-01-01

    Humans and animals frequently learn through observing or interacting with others. The local enhancement theory proposes that presence of social subjects in an environment facilitates other subjects' understanding of the environment. To explore the neural basis of this theory, we examined hippocampal place cells, which represent spatial information, in rats as they stayed in a small box while a demonstrator rat running on a separate, nearby linear track, and as they ran on the same track themselves. We found that place cell firing sequences during self-running on the track also appeared in the box. This cross-environment activation occurred even prior to any self-running experience on the track and was absent without a demonstrator. Our data thus suggest that social observation can facilitate the observer’s spatial representation of an environment without actual self-exploration. This finding may contribute to neural mechanisms of local enhancement. DOI: http://dx.doi.org/10.7554/eLife.18022.001

  13. 磷酸吡哆醛对培养的海马神经细胞形态学的影响%The effects of pyridoxal phosphate on morphological changes in cultured hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    耿美玉; 李静; 辛现良; 邓岗; 徐家敏; 管华诗

    2000-01-01

    The effects of pyridoxal phosphate (PLP) on the morphological changes of cultured hippocampal neurons celle were investigated. Hippocampal neurons from an 18 day old embryonic Wistar rat were prepared by enzymatic digestion and exposed to PLP in the low cell density condition. The results indicate that PLP at concentrations of 1, 10μm significantly promoted the elongation of the longest axon-like process in low cell density cultures. On the other hand, PLP showed no effects on other parameters such as the total length of dendrites, the numbe rs of branch points per axon, and the numbers of processes per soma. Ifenprodil and picrotoxin, although at the concentrations both counteracted the survival-promo ting activities of hippocampal neurons caused by PLP, failed to take any actions on the neurite elongation induced by PLP. In conclusion, PLP did have the elong ation-promoting activity for hippocampal neurons, the mechanisms underlying its positive effects on neurogenesis needs to be further elucidated.%实验观察磷酸吡哆醛对培养的海马神经细胞形态学的影响,选用妊娠18d Wistar大鼠胎鼠,采用酶消化法获得单个海马神经细胞,通过原代低密度细胞培养法观察磷酸吡哆醛 (PLP)对其形态学的影响.结果表明:在浓度为1,10μ m时,能明显地促进海马神经细胞轴突的伸展,但对树突总长度、每个轴突上的分叉数及胞体的突起数均无明显影响;Ifen prodil和Picrotoxin尽管能明显拮抗PLP介导的神经细胞营养作用,但对PLP的促神经细胞伸展作用却无明显影响.总之,认为PLP致所以具有促海马神经细胞轴突伸展作用,不是由于P LP介导的神经细胞的营养增加,其详细机理有待于进一步探讨.

  14. Adiponectin protects rat hippocampal neurons against excitotoxicity

    OpenAIRE

    Qiu, Guang; Wan, Ruiqian; Hu, Jingping; Mattson, Mark P.; Spangler, Edward; Liu, Shan; Yau, Suk-yu; Lee, Tatia M. C.; Gleichmann, Marc; Ingram, Donald K.; So, Kwok-Fai; Zou, Sige

    2010-01-01

    Adiponectin exerts multiple regulatory functions in the body and in the hypothalamus primarily through activation of its two receptors, adiponectin receptor1 and adiponectin receptor 2. Recent studies have shown that adiponectin receptors are widely expressed in other areas of the brain including the hippocampus. However, the functions of adiponectin in brain regions other than the hypothalamus are not clear. Here, we report that adiponectin can protect cultured hippocampal neurons against ka...

  15. Phenolic Compounds Protect Cultured Hippocampal Neurons against Ethanol-Withdrawal Induced Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Marianna E. Jung

    2009-04-01

    Full Text Available Ethanol withdrawal is linked to elevated oxidative damage to neurons. Here we report our findings on the contribution of phenolic antioxidants (17β-estradiol, p-octyl-phenol and 2,6-di-tert-butyl-4-methylphenol to counterbalance sudden ethanol withdrawal-initiated oxidative events in hippocampus-derived cultured HT-22 cells. We showed that ethanol withdrawal for 4 h after 24-h ethanol treatment provoked greater levels of oxidative damage than the preceding ethanol exposure. Phenolic antioxidant treatment either during ethanol exposure or ethanol withdrawal only, however, dose-dependently reversed cellular oxidative damage, as demonstrated by the significantly enhanced cell viability, reduced malondialdehyde production and protein carbonylation, compared to untreated cells. Interestingly, the antioxidant treatment schedule had no significant impact on the observed neuroprotection. In addition, the efficacy of the three phenolic compounds was practically equipotent in protecting HT-22 cells in spite of predictions based on an in silico study and a cell free assay of lipid peroxidation. This finding implies that free-radical scavenging may not be the sole factor responsible for the observed neuroprotection and warrants further studies to establish, whether the HT-22 line is indeed a suitable model for in vitro screening of antioxidants against EW-related neuronal damage.

  16. The GABAA receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, Jens; Zimmer, Jens

    2003-01-01

    The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneu...

  17. Theta-burst stimulation of hippocampal slices induces network-level calcium oscillations and activates analogous gene transcription to spatial learning.

    Directory of Open Access Journals (Sweden)

    Graham K Sheridan

    Full Text Available Over four decades ago, it was discovered that high-frequency stimulation of the dentate gyrus induces long-term potentiation (LTP of synaptic transmission. LTP is believed to underlie how we process and code external stimuli before converting it to salient information that we store as 'memories'. It has been shown that rats performing spatial learning tasks display theta-frequency (3-12 Hz hippocampal neural activity. Moreover, administering theta-burst stimulation (TBS to hippocampal slices can induce LTP. TBS triggers a sustained rise in intracellular calcium [Ca2+]i in neurons leading to new protein synthesis important for LTP maintenance. In this study, we measured TBS-induced [Ca2+]i oscillations in thousands of cells at increasing distances from the source of stimulation. Following TBS, a calcium wave propagates radially with an average speed of 5.2 µm/s and triggers multiple and regular [Ca2+]i oscillations in the hippocampus. Interestingly, the number and frequency of [Ca2+]i fluctuations post-TBS increased with respect to distance from the electrode. During the post-tetanic phase, 18% of cells exhibited 3 peaks in [Ca2+]i with a frequency of 17 mHz, whereas 2.3% of cells distributed further from the electrode displayed 8 [Ca2+]i oscillations at 33 mHz. We suggest that these observed [Ca2+]i oscillations could lead to activation of transcription factors involved in synaptic plasticity. In particular, the transcription factor, NF-κB, has been implicated in memory formation and is up-regulated after LTP induction. We measured increased activation of NF-κB 30 min post-TBS in CA1 pyramidal cells and also observed similar temporal up-regulation of NF-κB levels in CA1 neurons following water maze training in rats. Therefore, TBS of hippocampal slice cultures in vitro can mimic the cell type-specific up-regulations in activated NF-κB following spatial learning in vivo. This indicates that TBS may induce similar transcriptional changes to

  18. Adolescent olanzapine sensitization is correlated with hippocampal stem cell proliferation in a maternal immune activation rat model of schizophrenia.

    Science.gov (United States)

    Chou, Shinnyi; Jones, Sean; Li, Ming

    2015-08-27

    Previous work established that repeated olanzapine (OLZ) administration in normal adolescent rats induces a sensitization effect (i.e. increased behavioral responsiveness to drug re-exposure) in the conditioned avoidance response (CAR) model. However, it is unclear whether the same phenomenon can be detected in animal models of schizophrenia. The present study explored the generalizability of OLZ sensitization from healthy animals to a preclinical neuroinflammatory model of schizophrenia in the CAR. Maternal immune activation (MIA) was induced via polyinosinic:polycytidylic acid (PolyI:C) administration into pregnant dams. Behavioral assessments of offspring first identified decreased maternal separation-induced pup ultrasonic vocalizations and increased amphetamine-induced hyperlocomotion in animals prenatally exposed to PolyI:C. In addition, repeated adolescent OLZ administration confirmed the generalizability of the sensitization phenomenon. Using the CAR test, adolescent MIA animals displayed a similar increase in behavioral responsiveness after repeated OLZ exposure during both the repeated drug test days as well as a subsequent challenge test. Neurobiologically, few studies examining the relationship between hippocampal cell proliferation and survival and either antipsychotic exposure or MIA have incorporated concurrent behavioral changes. Thus, the current study also sought to reveal the correlation between OLZ behavioral sensitization in the CAR and hippocampal cell proliferation and survival. 5'-bromodeoxyuridine immunohistochemistry identified a positive correlation between the magnitude of OLZ sensitization (i.e. change in avoidance suppression induced by OLZ across days) and hippocampal cell proliferation. The implications of the relationship between behavioral and neurobiological results are discussed.

  19. Transsynaptic neuronal loss induced in hippocampal slice cultures by a herpes simplex virus vector expressing the GluR6 subunit of the kainate receptor.

    OpenAIRE

    Bergold, P J; Casaccia-Bonnefil, P; Zeng, X. L.; Federoff, H. J.

    1993-01-01

    Patients with severe temporal lobe epilepsy lose neurons within the CA3 and hilar regions of the hippocampus. Loss of CA3 and hilar neurons was also induced by transducing organotypic hippocampal slice cultures with a replication-defective herpes simplex virus (HSV) vector expressing the GluR6 kainate subtype of the glutamate receptor (HSVGluR6). In transduced fibroblasts, HSVGluR6 expressed a M(r) 115,000 protein that reacted with anti-GluR6 serum. After exposure of fibroblast to HSVGluR6, a...

  20. Effects of low intensity radiofrequency electromagnetic fields on electrical activity in rat hippocampal slices.

    Science.gov (United States)

    Tattersall, J E; Scott, I R; Wood, S J; Nettell, J J; Bevir, M K; Wang, Z; Somasiri, N P; Chen, X

    2001-06-15

    Slices of rat hippocampus were exposed to 700 MHz continuous wave radiofrequency (RF) fields (25.2-71.0 V m(-1), 5-15 min exposure) in a stripline waveguide. At low field intensities, the predominant effect on the electrically evoked field potential in CA1 was a potentiation of the amplitude of the population spike by up to 20%, but higher intensity fields could produce either increases or decreases of up to 120 and 80%, respectively, in the amplitude of the population spike. To eliminate the possibility of RF-induced artefacts due to the metal stimulating electrode, the effect of RF exposure on spontaneous epileptiform activity induced in CA3 by 4-aminopyridine (50-100 microM) was investigated. Exposure to RF fields (50.0 V m(-1)) reduced or abolished epileptiform bursting in 36% of slices tested. The maximum field intensity used in these experiments, 71.0 V m(-1), was calculated to produce a specific absorption rate (SAR) of between 0.0016 and 0.0044 W kg(-1) in the slices. Measurements with a Luxtron fibreoptic probe confirmed that there was no detectable temperature change (+/- 0.1 degrees C) during a 15 min exposure to this field intensity. Furthermore, imposed temperature changes of up to 1 degrees C failed to mimic the effects of RF exposure. These results suggest that low-intensity RF fields can modulate the excitability of hippocampal tissue in vitro in the absence of gross thermal effects. The changes in excitability may be consistent with reported behavioural effects of RF fields.

  1. ESTRADIOL-INDUCED ENHANCEMENT OF OBJECT MEMORY CONSOLIDATION INVOLVES HIPPOCAMPAL ERK ACTIVATION AND MEMBRANE-BOUND ESTROGEN RECEPTORS

    OpenAIRE

    Fernandez, Stephanie M.; Michael C. Lewis; Pechenino, Angela S.; Harburger, Lauren L.; Orr, Patrick T.; Gresack, Jodi E.; Schafe, Glenn E.; Frick, Karyn M.

    2008-01-01

    The extracellular signal-regulated kinase (ERK) pathway is critical for various forms of learning and memory, and is activated by the potent estrogen, 17β-estradiol (E2). Here, we asked whether E2 modulates memory via ERK activation and putative membrane-bound estrogen receptors (ERs). Using ovariectomized mice, we first demonstrate that intraperitoneal (i.p.) injection of 0.2 mg/kg E2 significantly increases dorsal hippocampal levels of phosphorylated ERK protein 1 hour after injection. Seco...

  2. Protective effects of plant seed extracts against amyloid β-induced neurotoxicity in cultured hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Yoshinori Okada

    2013-01-01

    Full Text Available Aim: Alzheimer′s disease (AD is characterized by large deposits of amyloid β (Aβ peptide. Aβ is known to increase reactive oxygen species (ROS production in neurons, leading to cell death. In this study, we screened 15 plant seeds′ aqueous extracts (PSAE for inhibitory effects on Aβ (25-35-induced cell death using hippocampus neurons (HIPN. Materials and Methods: Fifteen chosen plants were nine medical herbs (Japanese honeywort, luffa, rapeseed, Chinese colza, potherb mustard, Japanese radish, bitter melon, red shiso, corn, and kaiware radish and six general commercial plants (common bean, komatsuna, Qing geng cai, bell pepper, kale, and lettuce. PSAE were measured for total phenolic content (TPC with the Folin-Ciocalteu method, and the 2-diphenyl-1-picryl-hydrazyl (DPPH radical scavenging effect of each seed extract was measured. To find a protectant against Aβ-induced oxidative stress, we screened 15 PSAE using a 2′, 7′-dichlorofluorescein diacetate assay. To further unravel the anti-inflammatory effects of PSAE on Aβ-induced inflammation, PSAE were added to HIPN. The neuroprotective effects of the PSAE were evaluated by Cell Counting Kit-8 assay, measuring the cell viability in Aβ-induced HIPN. Results: TPC of 15 PSAE was in the range of 0.024-1.96 mg of chlorogenic acid equivalents/gram. The aqueous extracts showed antioxidant activities. Furthermore, intracellular ROS accumulation resulting from Aβ treatment was reduced when cells were treated with some PSAE. Kale, bitter melon, kaiware radish, red shiso, and corn inhibited tumor necrosis factor-alpha secretion by the Aβ-stimulated neurons and all samples except Japanese honeywort showed enhancement of cell survival. Conclusion: From these results, we suggest that some plant seed extracts offer protection against Aβ-mediated cell death.

  3. Increased neuroplasticity and hippocampal microglia activation in a mice model of rapid antidepressant treatment.

    Science.gov (United States)

    Muzio, Luca; Brambilla, Valentina; Calcaterra, Lorenza; D'Adamo, Patrizia; Martino, Gianvito; Benedetti, Francesco

    2016-09-15

    The search for biomarkers of antidepressant effects focused on pathways regulating synaptic plasticity, and on activated inflammatory markers. Repeated Sleep Deprivation (SD) provides a model treatment to reverse-translate antidepressant effects from in vivo clinical psychiatry to model organisms. We studied the effects of repeated SD alone (ASD) or combined with exercise on a slow spinning wheel (SSW), in 116 C57BL/6J male mice divided in three groups (ASD, SSW, untreated). Forced Swimming Test (FST) was used to detect antidepressant-like effects. Unbiased evaluation of the transcriptional responses were obtained in the hippocampus by Illumina Bead Chip Array system, then confirmed with real time PCR. Spine densities in granular neurons of the dentate gyrus (DG) were assayed by standard Golgi staining. Activation of Microglial/Macrophages cells was evaluated by immunufluorescence analysis for Iba1. Rates of cell proliferation was estimated pulsing mice with the S-phase tracer 5-Iodo-2'-deoxyuridine (IdU). All SD procedures caused a decreasing of floating time at FST, and increased expression of the immediate early gene Arc/Arg3.1. In addition, SSW also increased expression of the Microglia/Macrophages genes Iba-1 and chemokine receptors Cx3cR1 and CxcR4, of the canonical Wnt signaling gene Wnt7a, and of dendritic spines in CA4 neurons of the DG. SSW up-regulated both the number of Iba1+ cells and rates of cell proliferation in the subgranular region of the DG. The antidepressant-like effects of SD dissociated both, from hippocampal neuroplasticity in the DG (not occurring after ASD), and from microglial activation (not preventing behavioral response when occurring). The increase in dendritic spine density in the DG after SD and exercise was associated with an up-regulation of Wnt 7a, and with activation of the innate immune system of the brain. Increased Arc/Arg3.1 suggests however increased neuroplasticity, which could be common to all fast-acting antidepressants

  4. Dissociation of dorsal hippocampal regional activation under the influence of stress in freely behaving rats

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    Johannes ePassecker

    2011-10-01

    Full Text Available Stress has deleterious effects on brain, body and behaviour in humans and animals alike. The present work investigated how 30-minute acute photic stress exposure impacts on spatial information processing in the main subregions of the dorsal hippocampal formation (CA1, CA3 and Dentate Gyrus, a brain structure prominently implicated in memory and spatial representation. Recordings were performed from spatially tuned hippocampal and dentate gyrus cells in rats while animals foraged in a square arena for food. The stress procedure induced a decrease in firing frequencies in CA1 and CA3 place cells while sparing locational characteristics. In contrast to the CA1-CA3 network, acute stress failed to induce major changes in the DG neuronal population. These data demonstrate a clear dissociation of the effects of stress on the main hippocampal sub-regions. Our findings further support the notion of decreased hippocampal excitability arising from stress in areas CA1 and CA3, but not in dentate gyrus.

  5. Lithium ions in nanomolar concentration modulate glycine-activated chloride current in rat hippocampal neurons.

    Science.gov (United States)

    Solntseva, E I; Bukanova, J V; Kondratenko, R V; Skrebitsky, V G

    2016-03-01

    Lithium salts are successfully used to treat bipolar disorder. At the same time, according to recent data lithium may be considered as a candidate medication for the treatment of neurodegenerative disorders. The mechanisms of therapeutic action of lithium have not been fully elucidated. In particular, in the literature there are no data on the effect of lithium on the glycine receptors. In the present study we investigated the effect of Li(+) on glycine-activated chloride current (IGly) in rat isolated pyramidal hippocampal neurons using patch-clamp technique. The effects of Li(+) were studied with two glycine concentrations: 100 μM (EC50) and 500 μM (nearly saturating). Li(+) was applied to the cell in two ways: first, by 600 ms co-application with glycine through micropipette (short application), and, second, by addition to an extracellular perfusate for 10 min (longer application). Li(+) was used in the range of concentrations of 1 nM-1 mM. Short application of Li(+) caused two effects: (1) an acceleration of desensitization (a decrease in the time of half-decay, or "τ") of IGly induced by both 100 μM and 500 μM glycine, and (2) a reduction of the peak amplitude of the IGly, induced by 100 μM, but not by 500 μM glycine. Both effects were not voltage-dependent. Dose-response curves for both effects were N-shaped with two maximums at 100 nM and 1 mM of Li(+) and a minimum at 1 μM of Li(+). This complex form of dose-response may indicate that the process activated by high concentrations of lithium inhibits the process that is sensitive to low concentrations of lithium. Longer application of Li(+)caused similar effects, but in this case 1 μM lithium was effective and the dose-effect curves were not N-shaped. The inhibitory effect of lithium ions on glycine-activated current suggests that lithium in low concentrations is able to modulate tonic inhibition in the hippocampus. This important property of lithium should be considered when using this drug as a

  6. Protection of Hippocampal Neurogenesis from Toll-Like Receptor 4-Dependent Innate Immune Activation by Ablation of Prostaglandin E2 Receptor Subtype EP1 or EP2

    Science.gov (United States)

    Keene, C. Dirk; Chang, Rubens; Stephen, Christina; Nivison, Mary; Nutt, Samuel E.; Look, Amy; Breyer, Richard M.; Horner, Phillip J.; Hevner, Robert; Montine, Thomas J.

    2009-01-01

    Prostaglandin E2 is one of several eicosanoid products of the cyclooxygenase isozymes and is a key regulator of innate immune responses; it also possesses paracrine effects on mature neurons. The prostaglandin E2 receptor family consists of four subtypes of which EP1 and EP2 are known to be expressed by microglia. Lipopolysaccharide (LPS)-induced innate immune activation leads to the degeneration of intermediate progenitor cells (IPCs) that are destined for neuronal maturation in the hippocampal subgranular zone (SGZ); these cells can be identified by the expression of the transcription factor T-box brain gene 2 (Tbr2). Importantly, depletion of LPS-induced IPCs from the SGZ is suppressed by cyclooxygenase inhibitors. We therefore tested the hypothesis that either EP1 or EP2 is critical to LPS-induced depletion of Tbr2+ IPCs from the SGZ. Expression of either EP1 or EP2 was necessary for Toll-like receptor 4-dependent innate immune-mediated depletion of these Tbr2+ IPCs in mice. Moreover, EP1 activation was directly toxic to murine adult hippocampal progenitor cells; EP2 was not expressed by these cells. Finally, EP1 modulated the response of murine primary microglia cultures to LPS but in a manner distinct from EP2. These results indicate that prostaglandin E2 signaling via either EP1 or EP2 is largely to completely necessary for Toll-like receptor 4-dependent depletion of IPCs from the SGZ and suggest further pharmacological strategies to protect this important neurogenic niche. PMID:19389932

  7. HspB5/αB-crystallin increases dendritic complexity and protects the dendritic arbor during heat shock in cultured rat hippocampal neurons.

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    Bartelt-Kirbach, Britta; Moron, Margarethe; Glomb, Maximilian; Beck, Clara-Maria; Weller, Marie-Pascale; Golenhofen, Nikola

    2016-10-01

    The small heat shock protein ΗspΒ5 (αB-crystallin) exhibits generally cytoprotective functions and possesses powerful neuroprotective capacity in the brain. However, little is known about the mode of action of ΗspΒ5 or other members of the HspB family particularly in neurons. To get clues of the neuronal function of HspBs, we overexpressed several HspBs in cultured rat hippocampal neurons and investigated their effect on neuronal morphology and stress resistance. Whereas axon length and synapse density were not affected by any HspB, dendritic complexity was enhanced by HspB5 and, to a lesser extent, by HspB6. Furthermore, we could show that this process was dependent on phosphorylation, since a non-phosphorylatable mutant of HspB5 did not show this effect. Rarefaction of the dendritic arbor is one hallmark of several neurodegenerative diseases. To investigate if HspB5, which is upregulated at pathophysiological conditions, might be able to protect dendrites during such situations, we exposed HspB5 overexpressing neuronal cultures to heat shock. HspB5 prevented heat shock-induced rarefaction of dendrites. In conclusion, we identified regulation of dendritic complexity as a new function of HspB5 in hippocampal neurons. PMID:27085702

  8. GDNF selectively induces microglial activation and neuronal survival in CA1/CA3 hippocampal regions exposed to NMDA insult through Ret/ERK signalling.

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    Francesca Boscia

    Full Text Available The glial cell line-derived neurotrophic factor (GDNF is a potent survival factor for several neuronal populations in different brain regions, including the hippocampus. However, no information is available on the: (1 hippocampal subregions involved in the GDNF-neuroprotective actions upon excitotoxicity, (2 identity of GDNF-responsive hippocampal cells, (3 transduction pathways involved in the GDNF-mediated neuroprotection in the hippocampus. We addressed these questions in organotypic hippocampal slices exposed to GDNF in presence of N-methyl-D-aspartate (NMDA by immunoblotting, immunohistochemistry, and confocal analysis. In hippocampal slices GDNF acts through the activation of the tyrosine kinase receptor, Ret, without involving the NCAM-mediated pathway. Both Ret and ERK phosphorylation mainly occurred in the CA3 region where the two activated proteins co-localized. GDNF protected in a greater extent CA3 rather than CA1 following NMDA exposure. This neuroprotective effect targeted preferentially neurons, as assessed by NeuN staining. GDNF neuroprotection was associated with a significant increase of Ret phosphorylation in both CA3 and CA1. Interestingly, confocal images revealed that upon NMDA exposure, Ret activation occurred in microglial cells in the CA3 and CA1 following GDNF exposure. Collectively, this study shows that CA3 and CA1 hippocampal regions are highly responsive to GDNF-induced Ret activation and neuroprotection, and suggest that, upon excitotoxicity, such neuroprotection involves a GDNF modulation of microglial cell activity.

  9. Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation

    OpenAIRE

    Roozendaal, Benno; Nguyen, Bichngoc T.; Power, Ann E.; McGaugh, James L.

    1999-01-01

    Previously, we reported that bilateral excitotoxic lesions of the basolateral nucleus of the amygdala (BLA) block the enhancing effects of posttraining systemic or intrahippocampal glucocorticoid administration on memory for inhibitory avoidance training. The present study further examined the basis of this permissive influence of the BLA on hippocampal memory functioning. Immediate posttraining unilateral infusions of the specific glucocorticoid receptor agonist RU 28362 (11β,17β-dihydroxy-6...

  10. Brain activity evidence for recognition without recollection after early hippocampal damage

    Science.gov (United States)

    Düzel, E.; Vargha-Khadem, F.; Heinze, H. J.; Mishkin, M.

    2001-01-01

    Amnesic patients with early and seemingly isolated hippocampal injury show relatively normal recognition memory scores. The cognitive profile of these patients raises the possibility that this recognition performance is maintained mainly by stimulus familiarity in the absence of recollection of contextual information. Here we report electrophysiological data on the status of recognition memory in one of the patients, Jon. Jon's recognition of studied words lacks the event-related potential (ERP) index of recollection, viz., an increase in the late positive component (500–700 ms), under conditions that elicit it reliably in normal subjects. On the other hand, a decrease of the ERP amplitude between 300 and 500 ms, also reliably found in normal subjects, is well preserved. This so-called N400 effect has been linked to stimulus familiarity in previous ERP studies of recognition memory. In Jon, this link is supported by the finding that his recognized and unrecognized studied words evoked topographically distinct ERP effects in the N400 time window. These data suggest that recollection is more dependent on the hippocampal formation than is familiarity, consistent with the view that the hippocampal formation plays a special role in episodic memory, for which recollection is so critical. PMID:11438748

  11. The hippocampus and appetitive Pavlovian conditioning: effects of excitotoxic hippocampal lesions on conditioned locomotor activity and autoshaping.

    Science.gov (United States)

    Ito, Rutsuko; Everitt, Barry J; Robbins, Trevor W

    2005-01-01

    The hippocampus (HPC) is known to be critically involved in the formation of associations between contextual/spatial stimuli and behaviorally significant events, playing a pivotal role in learning and memory. However, increasing evidence indicates that the HPC is also essential for more basic motivational processes. The amygdala, by contrast, is important for learning about the motivational significance of discrete cues. This study investigated the effects of excitotoxic lesions of the rat HPC and the basolateral amygdala (BLA) on the acquisition of a number of appetitive behaviors known to be dependent on the formation of Pavlovian associations between a reward (food) and discrete stimuli or contexts: (1) conditioned/anticipatory locomotor activity to food delivered in a specific context and (2) autoshaping, where rats learn to show conditioned discriminated approach to a discrete visual CS+. While BLA lesions had minimal effects on conditioned locomotor activity, hippocampal lesions facilitated the development of both conditioned activity to food and autoshaping behavior, suggesting that hippocampal lesions may have increased the incentive motivational properties of food and associated conditioned stimuli, consistent with the hypothesis that the HPC is involved in inhibitory processes in appetitive conditioning.

  12. Neuropeptides and hippocampal neurogenesis.

    Science.gov (United States)

    Zaben, M J; Gray, W P

    2013-12-01

    Hippocampal neurogenesis is important for modulating the behavioural responses to stress and for certain forms of learning and memory. The mechanisms underlying the necessary coupling of neuronal activity to neural stem/progenitor cell (NSPC) function remain poorly understood. Within the dentate subgranular stem cell niche, local interneurons appear to play an important part in this excitation-neurogenesis coupling via GABAergic transmission, which promotes neuronal differentiation and integration. Neuropeptides such as neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and galanin have emerged as important mediators for signalling local and extrinsic interneuronal activity to subgranular zone precursors. Here we review the distribution of these neuropeptides and their receptors in the neurogenic area of the hippocampus and their precise effects on hippocampal neurogenesis. We also discuss neuropeptides' potential involvement in functional aspects of hippocampal neurogenesis particularly their involvement in the modulation of learning and memory and behavior responses.

  13. KCNQ/Kv7 channel activator flupirtine protects against acute stress-induced impairments of spatial memory retrieval and hippocampal LTP in rats.

    Science.gov (United States)

    Li, C; Huang, P; Lu, Q; Zhou, M; Guo, L; Xu, X

    2014-11-01

    Spatial memory retrieval and hippocampal long-term potentiation (LTP) are impaired by stress. KCNQ/Kv7 channels are closely associated with memory and the KCNQ/Kv7 channel activator flupirtine represents neuroprotective effects. This study aims to test whether KCNQ/Kv7 channel activation prevents acute stress-induced impairments of spatial memory retrieval and hippocampal LTP. Rats were placed on an elevated platform in the middle of a bright room for 30 min to evoke acute stress. The expression of KCNQ/Kv7 subunits was analyzed at 1, 3 and 12 h after stress by Western blotting. Spatial memory was examined by the Morris water maze (MWM) and the field excitatory postsynaptic potential (fEPSP) in the hippocampal CA1 area was recorded in vivo. Acute stress transiently decreased the expression of KCNQ2 and KCNQ3 in the hippocampus. Acute stress impaired the spatial memory retrieval and hippocampal LTP, the KCNQ/Kv7 channel activator flupirtine prevented the impairments, and the protective effects of flupirtine were blocked by XE-991 (10,10-bis(4-Pyridinylmethyl)-9(10H)-anthracenone), a selective KCNQ channel blocker. Furthermore, acute stress decreased the phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9 in the hippocampus, and flupirtine inhibited the reduction. These results suggest that the KCNQ/Kv7 channels may be a potential target for protecting both hippocampal synaptic plasticity and spatial memory retrieval from acute stress influences. PMID:25234320

  14. 2-aminoethoxydiphenyl borate or lanthanum potentiates transient receptor potential-like channels in rat CA1 hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Fengpeng Sun; Tian-ming Gao

    2010-01-01

    Expression of transient receptor potential(TRP)channels is widespread with transcripts distributed throughout the brain.All TRP channel subunits are activated following phospholipase C activation and form cation-selective ion channels.Previous studies examining the existence of TRP channels in hippocampal CA1 pyramidal neurons were based on cultured neurons.Therefore,their relevance for living tissue remains unclear.In the present study,patch-clamp recordings were conducted from CA1 pyramidal neurons in hippocampal slices from 7-day-old rats.Whole-cell currents were obtained from CA1 hippocampal neurons with potentiation effects of 2-aminoethoxydiphenyl borate and lanthanum,revealing that recorded experimental currents were characteristic TRP-like channel currents.Identification of rat hippocampal mRNA transcripts of TRPC4,TRPC5,TRPV1,TRPV2,and TRPV3 channels further verified the expression of characteristic TRP-like channels on rat CA1hippocampal neurons.

  15. Environmental enrichment rescues DYRK1A activity and hippocampal adult neurogenesis in TgDyrk1A.

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    Pons-Espinal, Meritxell; Martinez de Lagran, Maria; Dierssen, Mara

    2013-12-01

    Hippocampal adult neurogenesis disruptions have been suggested as one of the neuronal plasticity mechanisms underlying learning and memory impairment in Down syndrome (DS). However, it remains unknown whether specific candidate genes are implicated in these phenotypes in the multifactorial context of DS. Here we report that transgenic mice (TgDyrk1A) with overdosage of Dyrk1A, a DS candidate gene, show important alterations in adult neurogenesis including reduced cell proliferation rate, altered cell cycle progression and reduced cell cycle exit leading to premature migration, differentiation and reduced survival of newly born cells. In addition, less proportion of newborn hippocampal TgDyrk1A neurons are activated upon learning, suggesting reduced integration in learning circuits. Some of these alterations were DYRK1A kinase-dependent since we could rescue those using a DYRK1A inhibitor, epigallocatechin-3-gallate. Environmental enrichment also normalized DYRK1A kinase overdosage in the hippocampus, and rescued adult neurogenesis alterations in TgDyrk1A mice. We conclude that Dyrk1A is a good candidate to explain neuronal plasticity deficits in DS and that normalizing the excess of DYRK1A kinase activity either pharmacologically or using environmental stimulation can correct adult neurogenesis defects in DS. PMID:23969234

  16. Intrinsic monitoring of learning success facilitates memory encoding via the activation of the SN/VTA-Hippocampal loop.

    Science.gov (United States)

    Ripollés, Pablo; Marco-Pallarés, Josep; Alicart, Helena; Tempelmann, Claus; Rodríguez-Fornells, Antoni; Noesselt, Toemme

    2016-01-01

    Humans constantly learn in the absence of explicit rewards. However, the neurobiological mechanisms supporting this type of internally-guided learning (without explicit feedback) are still unclear. Here, participants who completed a task in which no external reward/feedback was provided, exhibited enhanced fMRI-signals within the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop) when successfully grasping the meaning of new-words. Importantly, new-words that were better remembered showed increased activation and enhanced functional connectivity between the midbrain, hippocampus, and ventral striatum. Moreover, enhanced emotion-related physiological measures and subjective pleasantness ratings during encoding were associated with remembered new-words after 24 hr. Furthermore, increased subjective pleasantness ratings were also related to new-words remembered after seven days. These results suggest that intrinsic-potentially reward-related-signals, triggered by self-monitoring of correct performance, can promote the storage of new information into long-term memory through the activation of the SN/VTA-Hippocampal loop, possibly via dopaminergic modulation of the midbrain. PMID:27644419

  17. Intrinsic monitoring of learning success facilitates memory encoding via the activation of the SN/VTA-Hippocampal loop

    Science.gov (United States)

    Ripollés, Pablo; Marco-Pallarés, Josep; Alicart, Helena; Tempelmann, Claus; Rodríguez-Fornells, Antoni; Noesselt, Toemme

    2016-01-01

    Humans constantly learn in the absence of explicit rewards. However, the neurobiological mechanisms supporting this type of internally-guided learning (without explicit feedback) are still unclear. Here, participants who completed a task in which no external reward/feedback was provided, exhibited enhanced fMRI-signals within the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop) when successfully grasping the meaning of new-words. Importantly, new-words that were better remembered showed increased activation and enhanced functional connectivity between the midbrain, hippocampus, and ventral striatum. Moreover, enhanced emotion-related physiological measures and subjective pleasantness ratings during encoding were associated with remembered new-words after 24 hr. Furthermore, increased subjective pleasantness ratings were also related to new-words remembered after seven days. These results suggest that intrinsic—potentially reward-related—signals, triggered by self-monitoring of correct performance, can promote the storage of new information into long-term memory through the activation of the SN/VTA-Hippocampal loop, possibly via dopaminergic modulation of the midbrain. DOI: http://dx.doi.org/10.7554/eLife.17441.001 PMID:27644419

  18. Transient Receptor Potential Vanilloid 4 Inhibits γ-Aminobutyric Acid-Activated Current in Hippocampal Pyramidal Neurons

    Science.gov (United States)

    Hong, Zhiwen; Tian, Yujing; Qi, Mengwen; Li, Yingchun; Du, Yimei; Chen, Lei; Liu, Wentao; Chen, Ling

    2016-01-01

    The balance between excitatory and inhibitory neurotransmitter systems is crucial for the modulation of neuronal excitability in the central nervous system (CNS). The activation of transient receptor potential vanilloid 4 (TRPV4) is reported to enhance the response of hippocampal glutamate receptors, but whether the inhibitory neurotransmitter system can be regulated by TRPV4 remains unknown. γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. Here, we show that application of transient receptor potential vanilloid 4 (TRPV4) synthetic (GSK1016790A or 4α-PDD) or endogenous agonist (5,6-EET) inhibited GABA-activated current (IGABA) in hippocampal CA1 pyramidal neurons, which was blocked by specific antagonists of TRPV4 and of GABAA receptors. GSK1016790A increased the phosphorylated AMP-activated protein kinase (p-AMPK) and decreased the phosphorylated protein kinase B (p-Akt) protein levels, which was attenuated by removing extracellular calcium or by a calcium/calmodulin-dependent protein kinase kinase-β antagonist. GSK1016790A-induced decrease of p-Akt protein level was sensitive to an AMPK antagonist. GSK1016790A-inhibited IGABA was blocked by an AMPK antagonist or a phosphatidyl inositol 3 kinase (PI3K) agonist. GSK1016790A-induced inhibition of IGABA was also significantly attenuated by a protein kinase C (PKC) antagonist but was unaffected by protein kinase A or calcium/calmodulin-dependent protein kinase II antagonist. We conclude that activation of TRPV4 inhibits GABAA receptor, which may be mediated by activation of AMPK and subsequent down-regulation of PI3K/Akt signaling and activation of PKC signaling. Inhibition of GABAA receptors may account for the neuronal hyperexcitability caused by TRPV4 activation.

  19. Long-term, repeated dose in vitro neurotoxicity of the glutamate receptor antagonist L-AP3, demonstrated in rat hippocampal slice cultures by using continuous propidium iodide incubation

    DEFF Research Database (Denmark)

    Kristensen, Bjarne W; Blaabjerg, Morten; Noraberg, Jens;

    2007-01-01

    Most in vitro models are only used to assess short-term effects of test compounds. However, as demonstrated here, hippocampal slice cultures can be used for long-term studies. The test compound used was the metabotropic glutamate receptor antagonist, L(+)-2-amino-3-phosphonopropionic acid (L-AP3)...

  20. Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment

    Directory of Open Access Journals (Sweden)

    Sonntag William E

    2011-10-01

    Full Text Available Abstract Background Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline. Methods Three independent cohorts of adult (12-13 months and aged (26-28 months F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG. Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6 and Iba1. Results We report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance. Conclusions These data demonstrate a

  1. Effect of acetylcholine receptors on the pain-related electrical activities in the hippocampal CA3 region of morphine-addicted rats

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    Guan Zeng Li

    2015-07-01

    Full Text Available Objective(s:To determine the effect of acetylcholine (ACh, pilocarpine, and atropine on pain evoked responses of pain excited neurons (PEN and pain inhibited neurons (PIN in hippocampal CA3 region of morphine addicted rats. Materials and Methods:Female Wistar rats, weighing between 230-260 g were used in this study. Morphine addicted rats were generated by subcutaneous injection of increasing concentrations of morphine hydrochloride for six days. Trains of electrical impulses applied to the sciatic nerve were used as noxious stimulation and the evoked electrical activities of PEN or PIN in hippocampal CA3 area were recorded using extracellular electrophysiological recording techniques in hippocampal slices. The effect of acetylcholine receptor stimulation byACh, the muscarinic agonist pilocarpine, and the muscarinic antagonist atropine on the pain evoked responses of pain related electrical activities was analyzed in hippocampal CA3 area of morphine addicted rats. Results:Intra-CA3 microinjection of ACh (2 μg/1 μl or pilocarpine (2 μg/1 μl decreased the discharge frequency and prolonged the firing latency of PEN, but increased the discharge frequency and shortened the firing inhibitory duration (ID of PIN. The intra-CA3 administration of atropine (0.5 μg/1 μl produced opposite effect. The peak activity of cholinergic modulators was 2 to 4 min later in morphine addicted rats compared to peak activity previously observed in normal rats. Conclusion: ACh dependent modulation of noxious stimulation exists in hippocampal CA3 area of morphine addicted rats. Morphine treatment may shift the sensitivity of pain related neurons towards a delayed response to muscarinergic neurotransmission in hippocampal CA3 region.

  2. The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Blaabjerg, M; Kristensen, Bjarne Winther; Bonde, C;

    2001-01-01

    The potential toxic effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and its interactions with the N-methyl-D-aspartate (NMDA) receptor were studied in hippocampal brain slice cultures, using densitometric measurements of the cellular....... The neurodegeneration induced by 2 mM ACPD was completely abolished by addition of 10 microM of the NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), while 20 microM of the 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainic acid receptor antagonist...

  3. Toward a self-wired active reconstruction of the hippocampal trisynaptic loop: DG-CA3

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    Gregory J. Brewer

    2013-10-01

    Full Text Available The mammalian hippocampus functions to encode and retrieve memories by transiently changing synaptic strengths, yet encoding in individual subregions for transmission between regions remains poorly understood. Toward the goal of better understanding the coding in the trisynaptic pathway from the dentate gyrus (DG to the CA3 and CA1, we report a novel microfabricated device that divides a micro-electrode array into two compartments of separate hippocampal network subregions connected by axons that grow through 3x10x400 μm tunnels. Gene expression by qPCR demonstrated selective enrichment of separate DG, CA3 and CA1 subregions. Reconnection of DG to CA3 altered burst dynamics associated with marked enrichment of GAD67 in DG and GFAP in CA3. Surprisingly, DG axon spike propagation was preferentially unidirectional to the CA3 region at 0.5 m/s with little reverse transmission. Therefore, select hippocampal subregions intrinsically self-wire in anatomically appropriate patterns and maintain their distinct subregion phenotype without external inputs

  4. Ethanol affects network activity in cultured rat hippocampus: mediation by potassium channels.

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    Eduard Korkotian

    Full Text Available The effects of ethanol on neuronal network activity were studied in dissociated cultures of rat hippocampus. Exposure to low (0.25-0.5% ethanol concentrations caused an increase in synchronized network spikes, and a decrease in the duration of individual spikes. Ethanol also caused an increase in rate of miniature spontaneous excitatory postsynaptic currents. Higher concentrations of ethanol eliminated network spikes. These effects were reversible upon wash. The effects of the high, but not the low ethanol were blocked by the GABA antagonist bicuculline. The enhancing action of low ethanol was blocked by apamin, an SK potassium channel antagonist, and mimicked by 1-EBIO, an SK channel opener. It is proposed that in cultured hippocampal networks low concentration of ethanol is associated with SK channel activity, rather than the GABAergic receptor.

  5. Prior Activation of Inositol 1,4,5-Trisphosphate Receptors Suppresses the Subsequent Induction of Long-Term Potentiation in Hippocampal CA1 Neurons

    Science.gov (United States)

    Fujii, Satoshi; Yamazaki, Yoshihiko; Goto, Jun-Ichi; Fujiwara, Hiroki; Mikoshiba, Katsuhiko

    2016-01-01

    We investigated the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) activated by preconditioning low-frequency afferent stimulation (LFS) in the subsequent induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential or the population…

  6. Zolpidem reduces hippocampal neuronal activity in freely behaving mice: a large scale calcium imaging study with miniaturized fluorescence microscope.

    Directory of Open Access Journals (Sweden)

    Tamara Berdyyeva

    Full Text Available Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal's state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼ 65% significantly decreasing the rate of calcium transients, and a small subset (3% showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders.

  7. Low doses of alcohol potentiate GABA sub B inhibition of spontaneous activity of hippocampal CA1 neurons in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Criado, J.R.; Thies, R. (Univ. of Oklahoma, Oklahoma City (United States))

    1991-03-11

    Low doses of alcohol facilitate firing of hippocampal neurons. Such doses also enhance the inhibitory actions of GABA. Alcohol is known to potentiate inhibition via GABA{sub A} receptors. However, the effects of alcohol on GABA{sub B} receptor function are not understood. Spontaneous activity of single units was recorded from CA1 neurons of male rats anesthetized with 1.0% halothane. Electrical recordings and local application of drugs were done with multi-barrel pipettes. CA1 pyramidal neurons fired spontaneous bursts of action potentials. Acute alcohol decreased the interval between bursts, a mild excitatory action. Alcohol also more than doubled the period of complete inhibition produced by local application of both GABA and baclofen. These data suggest that GABA{sub B}-mediated inhibition is also potentiated by low doses of alcohol.

  8. Space activities and global popular music culture

    Science.gov (United States)

    Wessels, Allison Rae; Collins, Patrick

    During the "space age" era, space activities appear increasingly as a theme in Western popular music, as they do in popular culture generally. In combination with the electronics and tele-communications revolution, "pop/rock" music has grown explosively during the space age to become an effectively global culture. From this base a number of trends are emerging in the pattern of influences that space activities have on pop music. The paper looks at the use of themes and imagery in pop music; the role of space technology in the modern "globalization" of pop music; and current and future links between space activities and pop music culture, including how public space programmes are affected by its influence on popular attitudes.

  9. The interplay of early-life stress, nutrition and immune activation programs adult hippocampal structure and function

    Directory of Open Access Journals (Sweden)

    Lianne eHoeijmakers

    2015-01-01

    Full Text Available Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity.

  10. Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD

    DEFF Research Database (Denmark)

    Thorsen, Thor S; Madsen, Kenneth L; Rebola, Nelson;

    2010-01-01

    interacting protein 1 (GRIP1). Pretreatment of cultured hippocampal neurons with FSC231 inhibited coimmunopreciptation of the AMPA receptor GluR2 subunit with PICK1. In agreement with inhibiting the role of PICK1 in GluR2 trafficking, FSC231 accelerated recycling of pHluorin-tagged GluR2 in hippocampal...... neurons after internalization in response to NMDA receptor activation. FSC231 blocked the expression of both long-term depression and long-term potentiation in hippocampal CA1 neurons from acute slices, consistent with inhibition of the bidirectional function of PICK1 in synaptic plasticity. Given...

  11. Effect of bone marrow stromal cell transplantation to the hippocampal CA1 region on electroencephalographic activity in epileptic rats

    Institute of Scientific and Technical Information of China (English)

    Hong Xu; Guowei Xu; Zhongtang Feng; Tinghua Wang; Jia Yang; Qingying Wu; Zhicheng Xiao

    2008-01-01

    BACKGROUND: Animal experiments have confirmed that bone marrow stromal cell (BMSC) transplantation can serve as a treatment for epilepsy.OBJECTIVE: BMSCs derived from green fluorescent protein (GFP) mice were transplanted into the hippocampal CA1 region of epileptic rats. The aim of the study was to record electroencephalogram (EEG), analyze survival and migration of BMSCs, and validate the effect of BMSC transplantation for the treatment of epilepsy.DESIGN, TIME AND SETTING: A randomized block design experiment was performed at the Institute of Neuroscience, Kunming Medical College from March 200.5 to February 2006.MATERIALS: Homozygous C57BL/6CrSIcTgN (acr-EGFP) OsbC 14-Y01 -FM 131 mice, 8-12 weeks of age, were selected for preparation of cell suspension. Sprague Dawley rats were selected for establishing epilepsy models.METHODS: Rats were randomly divided into 4 groups: control (n = 8), model (n = 8), normal saline (n = 24), and BMSC (n = 24). In the model, normal saline, and BMSC groups, epilepsy was established with penicillin (3×107 U/kg i.p. ×7 days). Rats in the BMSC group received a BMSC suspension derived fromgreen fluorescent protein mice into the right hippocampal CA1 region. Rats in the vehicle control group were injected with the same volume of normal saline into the hippocampal CA1 region.MAIN OUTCOME MEASURES: The electroencephalogram was used to monitor brain activity. Survival and migration of the transplanted BMSCs was observed using fluorescence microscopy at 1, 2, and 4 weeks after transplantation.RESULTS: In BMSC group, fluorescent cells were observed at the transplantation site and in the adjacent tissue, as well as in the tissue surrounding the needle tract, indicating the migration of implanted cells. Fluorescent cells were not detected in the vehicle control group. The electroencephalogram of the control animals exhibited 7-9 Hz α waves, with a wave amplitude < 50 μ V. In the model and vehicle control groups, random spike

  12. Prolonged adenosine A1 receptor activation in hypoxia and pial vessel disruption focal cortical ischemia facilitates clathrin-mediated AMPA receptor endocytosis and long-lasting synaptic inhibition in rat hippocampal CA3-CA1 synapses: differential regulation of GluA2 and GluA1 subunits by p38 MAPK and JNK.

    Science.gov (United States)

    Chen, Zhicheng; Xiong, Cherry; Pancyr, Cassandra; Stockwell, Jocelyn; Walz, Wolfgang; Cayabyab, Francisco S

    2014-07-16

    Activation of presynaptic adenosine A1 receptors (A1Rs) causes substantial synaptic depression during hypoxia/cerebral ischemia, but postsynaptic actions of A1Rs are less clear. We found that A1Rs and GluA2-containing AMPA receptors (AMPARs) form stable protein complexes from hippocampal brain homogenates and cultured hippocampal neurons from Sprague Dawley rats. In contrast, adenosine A2A receptors (A2ARs) did not coprecipitate or colocalize with GluA2-containing AMPARs. Prolonged stimulation of A1Rs with the agonist N(6)-cyclopentyladenosine (CPA) caused adenosine-induced persistent synaptic depression (APSD) in hippocampal brain slices, and APSD levels were blunted by inhibiting clathrin-mediated endocytosis of GluA2 subunits with the Tat-GluA2-3Y peptide. Using biotinylation and membrane fractionation assays, prolonged CPA incubation showed significant depletion of GluA2/GluA1 surface expression from hippocampal brain slices and cultured neurons. Tat-GluA2-3Y peptide or dynamin inhibitor Dynasore prevented CPA-induced GluA2/GluA1 internalization. Confocal imaging analysis confirmed that functional A1Rs, but not A2ARs, are required for clathrin-mediated AMPAR endocytosis in hippocampal neurons. Pharmacological inhibitors or shRNA knockdown of p38 MAPK and JNK prevented A1R-mediated internalization of GluA2 but not GluA1 subunits. Tat-GluA2-3Y peptide or A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine also prevented hypoxia-mediated GluA2/GluA1 internalization. Finally, in a pial vessel disruption cortical stroke model, a unilateral cortical lesion compared with sham surgery reduced hippocampal GluA2, GluA1, and A1R surface expression and also caused synaptic depression in hippocampal slices that was consistent with AMPAR downregulation and decreased probability of transmitter release. Together, these results indicate a previously unknown mechanism for A1R-induced persistent synaptic depression involving clathrin-mediated GluA2 and GluA1 internalization that

  13. Information in small neuronal ensemble activity in the hippocampal CA1 during delayed non-matching to sample performance in rats

    Directory of Open Access Journals (Sweden)

    Takahashi Susumu

    2009-09-01

    Full Text Available Abstract Background The matrix-like organization of the hippocampus, with its several inputs and outputs, has given rise to several theories related to hippocampal information processing. Single-cell electrophysiological studies and studies of lesions or genetically altered animals using recognition memory tasks such as delayed non-matching-to-sample (DNMS tasks support the theories. However, a complete understanding of hippocampal function necessitates knowledge of the encoding of information by multiple neurons in a single trial. The role of neuronal ensembles in the hippocampal CA1 for a DNMS task was assessed quantitatively in this study using multi-neuronal recordings and an artificial neural network classifier as a decoder. Results The activity of small neuronal ensembles (6-18 cells over brief time intervals (2-50 ms contains accurate information specifically related to the matching/non-matching of continuously presented stimuli (stimulus comparison. The accuracy of the combination of neurons pooled over all the ensembles was markedly lower than those of the ensembles over all examined time intervals. Conclusion The results show that the spatiotemporal patterns of spiking activity among cells in the small neuronal ensemble contain much information that is specifically useful for the stimulus comparison. Small neuronal networks in the hippocampal CA1 might therefore act as a comparator during recognition memory tasks.

  14. Urotensin Ⅱ inhibits electrical activity of hippocampal CA1 neurons by potentiating the GABAA receptor-mediated Cl- current

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To examine the effects of urotensin Ⅱ (UII) on the discharges of neurons in CA1 area of hippocampal slices by using extracellular recording technique. Results① In response to the application of UII (0.3, 3.0,30.0, 300.0 nmol/L, n =77) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 63/77 (81.8%) neurons were significantly decreased in a dose-dependent manner. ②Pretreatment with bicuculline( BIC, 100 μmol/L) , a specific GABAA receptor antagonist, led to a marked increase in the SDR of 6/7 (85.71% ) neurons in an epileptiform pattern. The increased discharges were not significantly changed after UII (30.0 nmol/L) was applied into the perfusate for 2 min. ③ Pretreatment with picrotoxin (PIC, 50 μmol/L) , a selective blocker of Cl- channel, led to an increase in the SDR of all 8/8 (100%) neurons. The increased discharges were not influenced by the UII (30.0 nmol/L) applied.④Application of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50 μmol/L) into the perfusate for 2 min also significantly augmented the SDR of 14/16 (87.5%) neurons , then UII (30.0 nmol/L) applied into the perfusate reduced the increased the SDR of all 14/14 ( 100% ) neurons. Conclusion These results suggest that UII may decrease neuronal activity by potentiating GABAA receptor-mediated Cl- current in hippocampal CA1 neurons, and involved with the mediation of nitric oxide.

  15. Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-β plaque formation in organotypic hippocampal slice cultures.

    Science.gov (United States)

    Hellwig, Sabine; Masuch, Annette; Nestel, Sigrun; Katzmarski, Natalie; Meyer-Luehmann, Melanie; Biber, Knut

    2015-01-01

    The role of microglia in amyloid-β (Aβ) deposition is controversial. In the present study, an organotypic hippocampal slice culture (OHSC) system with an in vivo-like microglial-neuronal environment was used to investigate the potential contribution of microglia to Aβ plaque formation. We found that microglia ingested Aβ, thereby preventing plaque formation in OHSCs. Conversely, Aβ deposits formed rapidly in microglia-free wild-type slices. The capacity to prevent Aβ plaque formation was absent in forebrain microglia from young adult but not juvenile 5xFamilial Alzheimer's disease (FAD) mice. Since no loss of Aβ clearance capacity was observed in both wild-type and cerebellar microglia from 5xFAD animals, the high Aβ1-42 burden in the forebrain of 5xFAD animals likely underlies the exhaustion of microglial Aβ clearance capacity. These data may therefore explain why Aβ plaque formation has never been described in wild-type mice, and point to a beneficial role of microglia in AD pathology. We also describe a new method to study Aβ plaque formation in a cell culture setting.

  16. Effects of Ganoderma lucidum spore powder on astrocyte expression and glutamine synthetase activity in the hippocampal region of epileptic rats

    Institute of Scientific and Technical Information of China (English)

    Shiling Zhang; Shuqiu Wang

    2008-01-01

    BACKGROUND: Recent studies have demonstrated that astrocyte dysfunction plays a central role in inhibiting epileptic seizures and that regulation of astrocyte function may be a new target for treatment of epilepsy.OBJECTIVE: To observe the effects of Ganoderma lucidum spore powder (GLSP) on astrocyte morphology and ghitamine synthetase (GS) activity in the hippocampal region of epileptic rats.DESIGN, TIME AND SETTING: A randomized, controlled animal experiment was performed at the Function Laboratory, College of Basic Medicine, Jiamusi University between October and December 2006.MATERIALS: A total of 30 Sprague Dawley (SD) rats were randomized to three groups (n = 10): control,model, and GLSP. GLSP was sourced from Jiamusi Wild Ganoderma Lucidum Planting Base and prepared to 30 g/L with physiological saline before use. Pentylenetetrazol (PTZ) (10 g/L) was provided by Sigma Company, USA.METHODS: The control group received intraperitoneal (i.p.) and intragastric (i.g.) physiological saline.Following epilepsy induction by i.p. administration of PTZ (35 mg/kg), rats from the model and GLSP groups were ig injected with physiological saline and GLSP (300 mg/kg), respectively. Each compound was administered once per day, for a total of 28 successive days. Epileptic seizure convulsions were graded 0-5. A higher grade indicated more severe epilepsy. Only those rats showing stage 2 or higher convulsions at least 5 times successively were included in further experiments.MAIN OUTCOME MEASURES: Immediately after injection, seizure activity was monitored for 30 minutes to determine the latent period and seizure duration; simultaneously, astrocyte numbers and GS activity in the hippocampal region of rats with epilepsy were detected by immunohistochemistry.RESULTS: All 30 rats were included in the final analysis. On day 28, following PTZ administration epileptic seizures were not found in the control group. In the GLSP group, rats exhibited rhythmic head nodding or facial spasms

  17. Estradiol-induced object memory consolidation in middle-aged female mice requires dorsal hippocampal ERK and PI3K activation

    OpenAIRE

    Fan, Lu; Zhao, Zaorui; Orr, Patrick T.; Chambers, Cassie H.; Michael C. Lewis; Frick, Karyn M.

    2010-01-01

    We previously demonstrated that dorsal hippocampal extracellular signal-regulated kinase (ERK) activation is necessary for 17β-estradiol (E2) to enhance novel object recognition in young ovariectomized mice (Fernandez et al., 2008). Here, we asked whether E2 has similar memory-enhancing effects in middle-aged and aged ovariectomized mice, and whether these effects depend on ERK and phosphatidylinositol 3-kinase (PI3K)/Akt activation. We first demonstrated that intracerebroventricular (ICV) E2...

  18. Slowing of hippocampal activity correlates with cognitive decline in early-onset Alzheimer’s disease. An MEG study with virtual electrodes.

    Directory of Open Access Journals (Sweden)

    Marjolein M.A. Engels

    2016-05-01

    Full Text Available Pathology in Alzheimer’s disease (AD starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG. The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using virtual MEG electrodes.We used resting-state MEG recordings from 27 early-onset AD patients (age 60.6 ± 5.4, 12 females, Mini Mental State examination (MMSE range: 19-28 and 26 cognitively healthy age- and gender-matched controls (age 61.8 ± 5.5, 14 females. Activity was reconstructed using beamformer-based virtual electrodes for 78 cortical regions and 6 hippocampal regions. Group differences in peak frequency and relative power in six frequency bands were identified using permutation testing. For the patients, spearman correlations between the MMSE scores and peak frequency or relative power were calculated. Moreover, receiver operator characteristic curves were plotted to estimate the diagnostic accuracy.We found a lower hippocampal peak frequency in AD compared to controls, which, in the patients, correlated positively with MMSE (r(25 = .61; p < .01 whereas hippocampal relative theta power correlated negatively with MMSE (r(25 = -.54; p < .01. Cortical peak frequency was also lower in AD in association areas. Furthermore, cortical peak frequency correlated positively with MMSE (r(25 = .43; p < 0.05. In line with this finding, relative theta power was higher in AD across the cortex, and relative alpha and beta power was lower in more circumscribed areas. The average cortical relative theta power was the best discriminator between AD and controls (sensitivity 82%; specificity 81%. Using beamformer-based virtual electrodes, we were able to detect hippocampal activity in AD. In AD, this hippocampal activity is slowed, and correlates better with cognition than the (slowed activity in cortical areas. On the other

  19. Sericin can reduce hippocampal neuronal apoptosis by activating the Akt signal transduction pathway in a rat model of diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Zhihong Chen; Yaqiang He; Chengjun Song; Zhijun Dong; Zhejun Su; Jingfeng Xue

    2012-01-01

    In the present study, a rat model of type 2 diabetes mellitus was established by continuous peritoneal injection of streptozotocin. Following intragastric perfusion of sericin for 35 days, blood glucose levels significantly reduced, neuronal apoptosis in the hippocampal CA1 region decreased, hippocampal phosphorylated Akt and nuclear factor kappa B expression were enhanced, but Bcl-xL/Bcl-2 associated death promoter expression decreased. Results demonstrated that sericin can reduce hippocampal neuronal apoptosis in a rat model of diabetes mellitus by regulating abnormal changes in the Akt signal transduction pathway.

  20. Electroosmotic push-pull perfusion: description and application to qualitative analysis of the hydrolysis of exogenous galanin in organotypic hippocampal slice cultures.

    Science.gov (United States)

    Rupert, Amy E; Ou, Y; Sandberg, M; Weber, S G

    2013-05-15

    We demonstrate here a method that perfuses a small region of an organotypic hippocampal culture with a solution containing an enzyme substrate, a neuropeptide. Perfusate containing hydrolysis products is continually collected and subsequently analyzed for the products of the enzymatic degradation of the peptide substrate. The driving force for perfusion is an electric field. The fused silica capillaries used as "push" and "pull" or "source" and "collection" capillaries have a ζ-potential that is negative and greater in magnitude than the tissue's ζ-potential. Thus, depending on the magnitudes of particular dimensions, the electroosmotic flow in the capillaries augments the fluid velocity in the tissue. The flow rate is not directly measured; however, we determine it using a finite-element approach. We have determined the collection efficiency of the system using an all d-amino acid internal standard. The flow rates are low, in the nL/min range, and adjustable by controlling the current or voltage in the system. The collection efficiency of the d-amino acid peptide internal standard is variable, increasing with increased current and thus electroosmotic flow rate. The collection efficiency can be rationalized in the context of a Peclet number. Electroosmotic push-pull perfusion of the neuropeptide galanin (gal1-29) through the extracellular space of an organotypic hippocampal culture results in its hydrolysis by ectopeptidase reactions occurring in the extracellular space. The products of hydrolysis were identified by MALDI-MS. Experiments at two levels of current (8-12 μA and 19-40 μA) show that the probability of seeing hydrolysis products (apparently from aminopeptidases) is greater in the Cornu Ammonis area 3 (CA3) than in the Cornu Ammonis area 1 (CA1) in the higher current experiments. In the lower current experiments, shorter peptide products of aminopeptidases (gal13-29 to gal20-19) are seen with greater frequency in CA3 than in CA1 but there is no

  1. Neuroprotection Promoted by Guanosine Depends on Glutamine Synthetase and Glutamate Transporters Activity in Hippocampal Slices Subjected to Oxygen/Glucose Deprivation.

    Science.gov (United States)

    Dal-Cim, Tharine; Martins, Wagner C; Thomaz, Daniel T; Coelho, Victor; Poluceno, Gabriela Godoy; Lanznaster, Débora; Vandresen-Filho, Samuel; Tasca, Carla I

    2016-05-01

    Guanosine (GUO) has been shown to act as a neuroprotective agent against glutamatergic excitotoxicity by increasing glutamate uptake and decreasing its release. In this study, a putative effect of GUO action on glutamate transporters activity modulation was assessed in hippocampal slices subjected to oxygen and glucose deprivation (OGD), an in vitro model of brain ischemia. Slices subjected to OGD showed increased excitatory amino acids release (measured by D-[(3)H]aspartate release) that was prevented in the presence of GUO (100 µM). The glutamate transporter blockers, DL-TBOA (10 µM), DHK (100 µM, selective inhibitor of GLT-1), and sulfasalazine (SAS, 250 µM, Xc(-) system inhibitor) decreased OGD-induced D-aspartate release. Interestingly, DHK or DL-TBOA blocked the decrease in glutamate release induced by GUO, whereas SAS did not modify the GUO effect. GUO protected hippocampal slices from cellular damage by modulation of glutamate transporters, however selective blockade of GLT-1 or Xc- system only did not affect this protective action of GUO. OGD decreased hippocampal glutamine synthetase (GS) activity and GUO recovered GS activity to control levels without altering the kinetic parameters of GS activity, thus suggesting GUO does not directly interact with GS. Additionally, the pharmacological inhibition of GS activity with methionine sulfoximine abolished the effect of GUO in reducing D-aspartate release and cellular damage evoked by OGD. Altogether, results in hippocampal slices subjected to OGD show that GUO counteracts the release of excitatory amino acids, stimulates the activity of GS, and decreases the cellular damage by modulation of glutamate transporters activity.

  2. Culture phenomenon analysis on the forest tour activity of China

    Institute of Scientific and Technical Information of China (English)

    Jiang Minjin

    2006-01-01

    This paper analyzes culture and forest culture, the intension of culture and forest culture, combines the understanding of the main cultural factor with the forest tour activity of China, analyzes the compatible phenomenon of Chinese forest culture and traditional culture, and explores culture of forest tourist site containing the meaning in forest tour. The author thinks the tour of forest culture which will be the important component of forest tour in forest culture,This paper puts forward simple questions existing in exploitation and advantage of forest tour culture, and proposes some countermeasures.

  3. D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures.

    Directory of Open Access Journals (Sweden)

    Alan C Foster

    Full Text Available N-methyl-D-aspartate (NMDA receptors play critical roles in synaptic transmission and plasticity. Activation of NMDA receptors by synaptically released L-glutamate also requires occupancy of co-agonist binding sites in the tetrameric receptor by either glycine or D-serine. Although D-serine appears to be the predominant co-agonist at synaptic NMDA receptors, the transport mechanisms involved in D-serine homeostasis in brain are poorly understood. In this work we show that the SLC1 amino acid transporter family members SLC1A4 (ASCT1 and SLC1A5 (ASCT2 mediate homo- and hetero-exchange of D-serine with physiologically relevant kinetic parameters. In addition, the selectivity profile of D-serine uptake in cultured rat hippocampal astrocytes is consistent with uptake mediated by both ASCT1 and ASCT2. Together these data suggest that SLC1A4 (ASCT1 may represent an important route of Na-dependent D-serine flux in the brain that has the ability to regulate extracellular D-serine and thereby NMDA receptor activity.

  4. DIFFERENTIAL EFFECTS OF CAFFEINE, PICROTOXIN, AND PENTYLENETETRAZOL ON HIPPOCAMPAL AFTERDISCHARGE ACTIVITY AND WET DOG SHAKES (JOURNAL VERSION)

    Science.gov (United States)

    The present experiment was conducted to identify changes in hippocampal after discharge (AD) parameters following administration of subconvulsant dosages (half of the convulsant dosage) of analeptics with known pharmacological action. Long Evans rats (N=104) with chronic bipolar ...

  5. Sericin can reduce hippocampal neuronal apoptosis by activating the Akt signal transduction pathway in a rat model of diabetes mellitus☆

    OpenAIRE

    Chen, Zhihong; He, Yaqiang; Song, Chengjun; Dong, Zhijun; Su, Zhejun; Xue, Jingfeng

    2012-01-01

    In the present study, a rat model of type 2 diabetes mellitus was established by continuous peritoneal injection of streptozotocin. Following intragastric perfusion of sericin for 35 days, blood glucose levels significantly reduced, neuronal apoptosis in the hippocampal CA1 region decreased, hippocampal phosphorylated Akt and nuclear factor kappa B expression were enhanced, but Bcl-xL/Bcl-2 associated death promoter expression decreased. Results demonstrated that sericin can reduce hippocampa...

  6. Inhibition of spontaneous network activity in neonatal hippocampal slices by energy substrates is not correlated with intracellular acidification.

    Science.gov (United States)

    Mukhtarov, Marat; Ivanov, Anton; Zilberter, Yuri; Bregestovski, Piotr

    2011-01-01

    Several energy substrates complementary to glucose, including lactate, pyruvate and β-hydroxybutyrate, serve as a fuel for neurons. It was reported recently that these substrates can substantially modulate cortical excitability in neonatal slices. However, complementary energy substrates (CES) can also induce an intracellular acidification when added exogenously. Therefore, action of CES on the neuronal properties governing excitability in neonatal brain slices may be underlain by a change in the cell energy status or by intracellular acidification, or both. Here, we attempt to elucidate these possibilities in neonatal hippocampus by recording neuronal population activity and monitoring intracellular pH. We show that a spontaneous network activity pattern, giant depolarizing potentials (GDPs), characteristic for the neonatal hippocampal slices exposed to artificial cerebrospinal fluid, is strongly inhibited by CES and this effect is unlikely to be caused by a subtle intracellular acidification induced by these compounds. Indeed, a much stronger intracellular acidification in the HCO(3) -free solution inhibited neither the GDP frequency nor the GDP amplitude. Therefore, modulation of neuronal energy homeostasis is the most likely factor underlying the effect of lactate, pyruvate and β-hydroxybutyrate on network excitability in neonatal brain slices.

  7. Differential Left Hippocampal Activation during Retrieval with Different Types of Reminders: An fMRI Study of the Reconsolidation Process

    Science.gov (United States)

    De Pino, Gabriela; Fernández, Rodrigo Sebastián; Villarreal, Mirta Fabiana; Pedreira, María Eugenia

    2016-01-01

    Consolidated memories return to a labile state after the presentation of cues (reminders) associated with acquisition, followed by a period of stabilization (reconsolidation). However not all cues are equally effective in initiating the process, unpredictable cues triggered it, predictable cues do not. We hypothesize that the different effects observed by the different reminder types on memory labilization-reconsolidation depend on a differential neural involvement during reminder presentation. To test it, we developed a declarative task and compared the efficacy of three reminder types in triggering the process in humans (Experiment 1). Finally, we compared the brain activation patterns between the different conditions using functional magnetic resonance imaging (fMRI) (Experiment 2). We confirmed that the unpredictable reminder is the most effective in initiating the labilization-reconsolidation process. Furthermore, only under this condition there was differential left hippocampal activation during its presentation. We suggest that the left hippocampus is detecting the incongruence between actual and past events and allows the memory to be updated. PMID:26991776

  8. Using activity theory to study cultural complexity in medical education

    NARCIS (Netherlands)

    Frambach, J.M.; Driessen, E.W.; Vleuten, C.P.M. van der

    2014-01-01

    There is a growing need for research on culture, cultural differences and cultural effects of globalization in medical education, but these are complex phenomena to investigate. Socio-cultural activity theory seems a useful framework to study cultural complexity, because it matches current views on

  9. Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available BACKGROUND: Excessive release of chelatable zinc from excitatory synaptic vesicles is involved in the pathogenesis of selective neuronal cell death following transient forebrain ischemia. The present study was designed to examine the neuroprotective effect of a membrane-permeable zinc chelator, clioquinol (CQ, in the CA1 region of the gerbil hippocampus after transient global ischemia. METHODOLOGY/PRINCIPAL FINDINGS: The common carotid arteries were occluded bilaterally, and CQ (10 mg/kg, i.p. was injected into gerbils once a day. The zinc chelating effect of CQ was examined with TSQ fluorescence and autometallography. Neuronal death, the expression levels of caspases and apoptosis inducing factor (AIF were evaluated using TUNEL, in situ hybridization and Western blotting, respectively. We were able to show for the first time that CQ treatment attenuates the ischemia-induced zinc accumulation in the CA1 pyramidal neurons, accompanied by less neuronal loss in the CA1 field of the hippocampus after ischemia. Furthermore, the expression levels of caspase-3, -9, and AIF were significantly decreased in the hippocampus of CQ-treated gerbils. CONCLUSIONS/SIGNIFICANCE: The present study indicates that the neuroprotective effect of CQ is related to downregulation of zinc-triggered caspase activation in the hippocampal CA1 region of gerbils with global ischemia.

  10. GDF-15 secreted from human umbilical cord blood mesenchymal stem cells delivered through the cerebrospinal fluid promotes hippocampal neurogenesis and synaptic activity in an Alzheimer's disease model.

    Science.gov (United States)

    Kim, Dong Hyun; Lee, Dahm; Chang, Eun Hyuk; Kim, Ji Hyun; Hwang, Jung Won; Kim, Ju-Yeon; Kyung, Jae Won; Kim, Sung Hyun; Oh, Jeong Su; Shim, Sang Mi; Na, Duk Lyul; Oh, Wonil; Chang, Jong Wook

    2015-10-15

    Our previous studies demonstrated that transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the hippocampus of a transgenic mouse model of Alzheimer's disease (AD) reduced amyloid-β (Aβ) plaques and enhanced cognitive function through paracrine action. Due to the limited life span of hUCB-MSCs after their transplantation, the extension of hUCB-MSC efficacy was essential for AD treatment. In this study, we show that repeated cisterna magna injections of hUCB-MSCs activated endogenous hippocampal neurogenesis and significantly reduced Aβ42 levels. To identify the paracrine factors released from the hUCB-MSCs that stimulated endogenous hippocampal neurogenesis in the dentate gyrus, we cocultured adult mouse neural stem cells (NSCs) with hUCB-MSCs and analyzed the cocultured media with cytokine arrays. Growth differentiation factor-15 (GDF-15) levels were significantly increased in the media. GDF-15 suppression in hUCB-MSCs with GDF-15 small interfering RNA reduced the proliferation of NSCs in cocultures. Conversely, recombinant GDF-15 treatment in both in vitro and in vivo enhanced hippocampal NSC proliferation and neuronal differentiation. Repeated administration of hUBC-MSCs markedly promoted the expression of synaptic vesicle markers, including synaptophysin, which are downregulated in patients with AD. In addition, in vitro synaptic activity through GDF-15 was promoted. Taken together, these results indicated that repeated cisterna magna administration of hUCB-MSCs enhanced endogenous adult hippocampal neurogenesis and synaptic activity through a paracrine factor of GDF-15, suggesting a possible role of hUCB-MSCs in future treatment strategies for AD.

  11. [Hippocampal stroke].

    Science.gov (United States)

    Rollnik, J D; Traitel, B; Dietrich, B; Lenz, O

    2015-02-01

    Unilateral cerebral ischemia of the hippocampus is very rare. This paper reviews the literature and presents the case of a 59-year-old woman with an amnestic syndrome due to a left hippocampal stroke. The patient suffered from retrograde amnesia which was most severe over the 2 days prior to presenting and a slight anterograde amnesia. In addition, a verbal memory disorder was confirmed 1 week after admission by neurological tests. As risk factors, arterial hypertension and a relative hyper-beta lipoproteinemia were found. This case shows that unilateral amnestic stroke, e.g. in the hippocampus region, may be the cause of an amnestic syndrome and should be included in the differential diagnostics.

  12. Role of cyclic nucleotide-gated channels in the modulation of mouse hippocampal neurogenesis.

    Directory of Open Access Journals (Sweden)

    Maria Vittoria Podda

    Full Text Available Neural stem cells generate neurons in the hippocampal dentate gyrus in mammals, including humans, throughout adulthood. Adult hippocampal neurogenesis has been the focus of many studies due to its relevance in processes such as learning and memory and its documented impairment in some neurodegenerative diseases. However, we are still far from having a complete picture of the mechanism regulating this process. Our study focused on the possible role of cyclic nucleotide-gated (CNG channels. These voltage-independent channels activated by cyclic nucleotides, first described in retinal and olfactory receptors, have been receiving increasing attention for their involvement in several brain functions. Here we show that the rod-type, CNGA1, and olfactory-type, CNGA2, subunits are expressed in hippocampal neural stem cells in culture and in situ in the hippocampal neurogenic niche of adult mice. Pharmacological blockade of CNG channels did not affect cultured neural stem cell proliferation but reduced their differentiation towards the neuronal phenotype. The membrane permeant cGMP analogue, 8-Br-cGMP, enhanced neural stem cell differentiation to neurons and this effect was prevented by CNG channel blockade. In addition, patch-clamp recording from neuron-like differentiating neural stem cells revealed cGMP-activated currents attributable to ion flow through CNG channels. The current work provides novel insights into the role of CNG channels in promoting hippocampal neurogenesis, which may prove to be relevant for stem cell-based treatment of cognitive impairment and brain damage.

  13. Activity-dependent regulation of the K/Cl transporter KCC2 membrane diffusion, clustering, and function in hippocampal neurons.

    Science.gov (United States)

    Chamma, Ingrid; Heubl, Martin; Chevy, Quentin; Renner, Marianne; Moutkine, Imane; Eugène, Emmanuel; Poncer, Jean Christophe; Lévi, Sabine

    2013-09-25

    The neuronal K/Cl transporter KCC2 exports chloride ions and thereby influences the efficacy and polarity of GABA signaling in the brain. KCC2 is also critical for dendritic spine morphogenesis and the maintenance of glutamatergic transmission in cortical neurons. Because KCC2 plays a pivotal role in the function of central synapses, it is of particular importance to understand the cellular and molecular mechanisms underlying its regulation. Here, we studied the impact of membrane diffusion and clustering on KCC2 function. KCC2 forms clusters in the vicinity of both excitatory and inhibitory synapses. Using quantum-dot-based single-particle tracking on rat primary hippocampal neurons, we show that KCC2 is slowed down and confined at excitatory and inhibitory synapses compared with extrasynaptic regions. However, KCC2 escapes inhibitory synapses faster than excitatory synapses, reflecting stronger molecular constraints at the latter. Interfering with KCC2-actin interactions or inhibiting F-actin polymerization releases diffusion constraints on KCC2 at excitatory but not inhibitory synapses. Thus, F-actin constrains KCC2 diffusion at excitatory synapses, whereas KCC2 is confined at inhibitory synapses by a distinct mechanism. Finally, increased neuronal activity rapidly increases the diffusion coefficient and decreases the dwell time of KCC2 at excitatory synapses. This effect involves NMDAR activation, Ca(2+) influx, KCC2 S940 dephosphorylation and calpain protease cleavage of KCC2 and is accompanied by reduced KCC2 clustering and ion transport function. Thus, activity-dependent regulation of KCC2 lateral diffusion and clustering allows for a rapid regulation of chloride homeostasis in neurons.

  14. Ezrin mediates neuritogenesis via down-regulation of RhoA activity in cultured cortical neurons.

    Directory of Open Access Journals (Sweden)

    Yosuke Matsumoto

    Full Text Available Neuronal morphogenesis is implicated in neuronal function and development with rearrangement of cytoskeletal organization. Ezrin, a member of Ezrin/Radixin/Moesin (ERM proteins links between membrane proteins and actin cytoskeleton, and contributes to maintenance of cellular function and morphology. In cultured hippocampal neurons, suppression of both radixin and moesin showed deficits in growth cone morphology and neurite extensions. Down-regulation of ezrin using siRNA caused impairment of netrin-1-induced axon outgrowth in cultured cortical neurons. However, roles of ezrin in the neuronal morphogenesis of the cultured neurons have been poorly understood. In this report, we performed detailed studies on the roles of ezrin in the cultured cortical neurons prepared from the ezrin knockdown (Vil2(kd/kd mice embryo that showed a very small amount of ezrin expression compared with the wild-type (Vil2(+/+ neurons. Ezrin was mainly expressed in cell body in the cultured cortical neurons. We demonstrated that the cultured cortical neurons prepared from the Vil2(kd/kd mice embryo exhibited impairment of neuritogenesis. Moreover, we observed increased RhoA activity and phosphorylation of myosin light chain 2 (MLC2, as a downstream effector of RhoA in the Vil2(kd/kd neurons. In addition, inhibition of Rho kinase and myosin II rescued the impairment of neuritogenesis in the Vil2(kd/kd neurons. These data altogether suggest a novel role of ezrin in the neuritogenesis of the cultured cortical neurons through down-regulation of RhoA activity.

  15. Changes in the proliferative activity of hippocampal neural stem cells from manganismus mice

    Institute of Scientific and Technical Information of China (English)

    Guohe Tan; Boning Yang; Guofu Tan; Bo Liang; Jiangu Gong; Xiaodong Ge; Songchao Guo

    2007-01-01

    's region was recorded as the performance of spatial memory. At the final two days of the water maze tests, all the animals were daily intraperitoneally injected with 50 mg/kg BrdU three times successively, once every 4 hours. At 24 hours after the final BrdU injection, all the animals were sacrificed and perfused, and their brains were harvested, fixed and successively sliced at coronary plane on a freezing microtome. Distribution and number of BrdU-positive cells in the subgranular zone ofhippocampus of brains of experimental animas were detected respectively by immunohistochemistry for reflecting the proliferation of NSCs. Single-factor analysis of variance was used for comparing the difference of measurement data. Linear correlation analysis was used among the performance record in Morris water maze test, the number of BrdU-immunopositive cells and the dose of manganism.MAIN OUTCOME MEASURES: Learning and memory ability and the number of hippocampal NSCs of mice in each group.RESULTS: ①Performance of mice in Morris water maze: In the place navigation test, there was a significant retarded learning in mice of high-dose manganism group from the 3rd day as compared with control group (P < 0.01). Till the 5th day, escape latency of mice in each manganism group was prolonged,and learning performance was significantly decreased (P < 0.05), while swimming speed did not affect above results. In the spatial probe test, the average frequency of middle- and high-dose manganism groups was 1.17±1.60 and 0.80±1.10, respectively, and decreased remarkably than that of control group which was 4.86 ±1.35 (P < 0.01), indicating memory ability was decreased; while the average frequency of low-dose manganism group did not differ obviously from that of control group (P =0.066) although it was 2.67 ± 3.27.The difference of swimming speed in each group was still of no statistic significance (P > 0.05). ②Effect of manganism on the number of NSCs: After counting, the average

  16. Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay.

    Directory of Open Access Journals (Sweden)

    J Matthew Mahoney

    Full Text Available Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation.

  17. Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay.

    Science.gov (United States)

    Mahoney, J Matthew; Titiz, Ali S; Hernan, Amanda E; Scott, Rod C

    2016-01-01

    Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation. PMID:26866597

  18. Trafficking and surface expression of hyperpolarization-activated cyclic nucleotide-gated channels in hippocampal neurons

    NARCIS (Netherlands)

    Y. Noam; Q. Zha; L. Phan; R.L. Wu; D.M. Chetkovich; W.J. Wadman; T.Z. Baram

    2010-01-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels mediate the hyperpolarization-activated current I(h) and thus play important roles in the regulation of brain excitability. The subcellular distribution pattern of the HCN channels influences the effects that they exert on the proper

  19. Capsazepine抑制培养海马神经元网络线粒体转运%Capsazepine inhibits mitochondrial transport in cultured hippocampal neuronal networks of rat

    Institute of Scientific and Technical Information of China (English)

    付敏; 潘丽洁; 孙朝晖; 左焕琮; 谢佐平

    2009-01-01

    capsazepine(CZP)是辣椒素的合成类似物,也是野香草型瞬时感受器电位通道1(TRPV1)的选择性抑制剂.TRPV1在体内有广泛的表达谱,使CZP有广泛的作用位点.除此之外,以往的研究结果表明CZP除了作用于TRPVI外还有更复杂的信号通路.本课题研究了CZP对体外培养的大鼠海马神经元网络内线粒体转运的作用并分析其可能机制.结果显示:20 μmol/L的CZP可有效抑制原代培养海马神经元网络中的线粒体转运.CZP急性作用不引起胞内钙离子浓度的升高,也不引起细胞的凋亡.胞外更换为无外钙记录液,或者将GSK3g抑制剂SB415286与CZP共孵育,均不影响CZP对线粒体转运的抑制作用.然而,将BAPTA-AM与CZP共孵育,抑制了CZP对线粒体转运的抑制作用.本研究结果表明,CZP直接通过胞内钙信号通路影响神经元的线粒体转运,与胞外钙流或转运蛋白的磷酸化无关.%Capsazepine is a ByntlIetic analogue of capsaicin and a selective inhibitor of transient receptor potential vanilloid 1 channel (TRPV1).TRPV1 has wide expression profile,providing extensive targets for capsazepine.Evidence from previous studies showed that capsazepine acted more complex effects through other than TRPV1 signal pathway.In this study.we examined its effect and underlying mechanisms on mitochondrial transport of cultured hippecampal neurons in rats.The data showed that the number of the moving mitochondria in primarily cultured hippocampal neurons was remarkably decreased by 20 μmol/L capsazepine.Contradicted to previous study,the intracellular calcium concentration was not elevated.Capsazepine did not induce cell death in acute incubation.The inhibitory effect of capsasepine was not prevented by co-application of SB415286,the inhibitor of GSK313 or by replacing extracellular recording solution to calcium-free saline,but prevented by co-application of BAPTA-AM.These results indicated that capsazepine inhibited mitochondrial trans

  20. Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD

    OpenAIRE

    Hayes, Jasmeet Pannu; LaBar, Kevin S.; McCarthy, Gregory; Selgrade, Elizabeth; Nasser, Jessica; Dolcos, Florin; Morey , Rajendra A.

    2010-01-01

    Neurobiological models of posttraumatic stress disorder (PTSD) suggest that altered activity in the medial temporal lobes (MTL) during encoding of traumatic memories contribute to the development and maintenance of the disorder. However, there is little direct evidence in the PTSD literature to support these models. The goal of the present study was to examine MTL activity during trauma encoding in combat veterans using the subsequent memory paradigm. Fifteen combat veterans diagnosed with PT...

  1. A Transcriptional Mechanism Integrating Inputs from Extracellular Signals to Activate Hippocampal Stem Cells

    OpenAIRE

    Andersen, Jimena; Urbán, Noelia; Achimastou, Angeliki; Ito, Ayako; Simic, Milesa; Ullom, Kristy; Martynoga, Ben; Lebel, Mélanie; Göritz, Christian; Frisén, Jonas; Nakafuku, Masato; Guillemot, François

    2014-01-01

    Summary The activity of adult stem cells is regulated by signals emanating from the surrounding tissue. Many niche signals have been identified, but it is unclear how they influence the choice of stem cells to remain quiescent or divide. Here we show that when stem cells of the adult hippocampus receive activating signals, they first induce the expression of the transcription factor Ascl1 and only subsequently exit quiescence. Moreover, lowering Ascl1 expression reduces the proliferation rate...

  2. The Cultural Impact on the Traditional Spring Festival Activities

    Institute of Scientific and Technical Information of China (English)

    刘琳琳

    2015-01-01

    Spring Festival will surely be considered as the most important festival among Chinese colorful occasions.This study attempts to analyze several typical rituals of Spring Festival from the cultural aspects,digging out the cultural factors and cultur-al connotation from the activity like the Family Reunion Dinner,Spring Couplets,the Spring Festival Gala,etc.

  3. Chronic hypoxia induces the activation of the Wnt/β-catenin signaling pathway and stimulates hippocampal neurogenesis in wild-type and APPswe-PS1ΔE9 transgenic mice in vivo

    Science.gov (United States)

    Varela-Nallar, Lorena; Rojas-Abalos, Macarena; Abbott, Ana C.; Moya, Esteban A.; Iturriaga, Rodrigo; Inestrosa, Nibaldo C.

    2014-01-01

    Hypoxia modulates proliferation and differentiation of cultured embryonic and adult stem cells, an effect that includes β-catenin, a key component of the canonical Wnt signaling pathway. Here we studied the effect of mild hypoxia on the activity of the Wnt/β-catenin signaling pathway in the hippocampus of adult mice in vivo. The hypoxia-inducible transcription factor-1α (HIF-1α) was analyzed as a molecular control of the physiological hypoxic response. Exposure to chronic hypoxia (10% oxygen for 6–72 h) stimulated the activation of the Wnt/β-catenin signaling pathway. Because the Wnt/β-catenin pathway is a positive modulator of adult neurogenesis, we evaluated whether chronic hypoxia was able to stimulate neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus. Results indicate that hypoxia increased cell proliferation and neurogenesis in adult wild-type mice as determined by Ki67 staining, Bromodeoxyuridine (BrdU) incorporation and double labeling with doublecortin (DCX). Chronic hypoxia also induced neurogenesis in a double transgenic APPswe-PS1ΔE9 mouse model of Alzheimer’s disease (AD), which shows decreased levels of neurogenesis in the SGZ. Our results show for the first time that exposure to hypoxia in vivo can induce the activation of the Wnt/β-catenin signaling cascade in the hippocampus, suggesting that mild hypoxia may have a therapeutic value in neurodegenerative disorders associated with altered Wnt signaling in the brain and also in pathological conditions in which hippocampal neurogenesis is impaired. PMID:24574965

  4. Chronic hypoxia induces the in vivo activation of the Wnt/β-catenin signaling pathway and stimulates hippocampal neurogenesis in wild-type and APPswe-PS1deltaE9 transgenic mice

    Directory of Open Access Journals (Sweden)

    Lorena eVarela-Nallar

    2014-02-01

    Full Text Available Hypoxia modulates proliferation and differentiation of cultured embryonic and adult stem cells, an effect that includes β-catenin a key component of the canonical Wnt signaling pathway. Here we studied in vivo the effect of mild hypoxia on the activity of the Wnt/β-catenin signaling pathway in the hippocampus of adult mice. As a molecular control of the physiological hypoxic response the hypoxia-inducible transcription factor-1α (HIF-1α was analyzed. Exposure to chronic hypoxia (10% oxygen for 6-72 h stimulated the activation of the Wnt/β-catenin signaling pathway. Because the Wnt/β-catenin pathway is a positive modulator of adult neurogenesis, we evaluated whether chronic hypoxia was able to stimulate neurogenesis in the subgranular zone (SGZ of the hippocampal dentate gyrus. Results indicate that hypoxia increased cell proliferation and neurogenesis in adult wild-type mice as determined by Ki67 staining, BrdU incorporation and double labeling with doublecortin. Chronic hypoxia also induced neurogenesis in double transgenic APPswe-PS1deltaE9 mouse model of Alzheimer’s disease (AD, which shows decreased levels of neurogenesis at the SGZ. Our results show for the first time that in vivo exposure to hypoxia can induce the activation of the Wnt/β-catenin signaling cascade in the hippocampus, suggesting that mild hypoxia may have a therapeutic value in neurodegenerative disorder associated with altered Wnt signaling in the brain and also in pathological conditions in which hippocampal neurogenesis is impaired.

  5. Slowing of hippocampal activity correlates with cognitive decline in early-onset Alzheimer’s disease. An MEG study with virtual electrodes.

    OpenAIRE

    Engels, Marjolein M. A.; Arjan eHillebrand; van der Flier, Wiesje M; Stam, Cornelis J; Philip eScheltens; van Straaten, Elisabeth C. W.

    2016-01-01

    Pathology in Alzheimer’s disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using virtual MEG electrodes.We used resting-state MEG recordings from 27 early-onset AD patients (age 60.6 ± 5.4, 12 females, Mini Mental State examination (MMSE) ran...

  6. Slowing of Hippocampal Activity Correlates with Cognitive Decline in Early Onset Alzheimer’s Disease. An MEG Study with Virtual Electrodes

    OpenAIRE

    Engels, Marjolein M. A.; Hillebrand, Arjan; van der Flier, Wiesje M; Stam, Cornelis J; Scheltens, Philip; van Straaten, Elisabeth C. W.

    2016-01-01

    Pathology in Alzheimer’s disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using “virtual MEG electrodes”. We used resting-state MEG recordings from 27 early onset AD patients [age 60.6 ± 5.4, 12 females, mini-mental state examination (MMSE) ...

  7. Activation of the hippocampal complex during tactile maze solving in congenitally blind subjects

    DEFF Research Database (Denmark)

    Gagnon, Léa; Schneider, Fabien C; Siebner, Hartwig R;

    2012-01-01

    for their lack of vision. Little is known, however, about the neural mechanisms underlying spatial navigation in blind individuals in settings where these cues are absent. We therefore measured behavioural performance and blood oxygenation-level dependant (BOLD) responses using functional magnetic resonance...... and parahippocampus, occipital cortex and fusiform gyrus. Blindfolded sighted controls did not show increased BOLD responses in these areas; instead they activated the caudate nucleus and thalamus. Both groups activated the precuneus during tactile maze navigation. We conclude that cross-modal plastic processes allow...

  8. ALTERED HIPPOCAMPAL NEUROGENESIS AND AMYGDALAR NEURONAL ACTIVITY IN ADULT MICE WITH REPEATED EXPERIENCE OF AGGRESSION

    Directory of Open Access Journals (Sweden)

    Dmitriy eSmagin

    2015-12-01

    Full Text Available The repeated experience of winning in a social conflict setting elevates levels of aggression and may lead to violent behavioral patterns. Here we use a paradigm of repeated aggression and fighting deprivation to examine changes in behavior, neurogenesis, and neuronal activity in mice with positive fighting experience. We show that for males, repeated positive fighting experience induces persistent demonstration of aggression and stereotypic behaviors in daily agonistic interactions, enhances aggressive motivation, and elevates levels of anxiety. When winning males are deprived of opportunities to engage in further fights, they demonstrate increased levels of aggressiveness. Positive fighting experience results in increased levels of progenitor cell proliferation and production of young neurons in the hippocampus. This increase is not diminished after a fighting deprivation period. Furthermore, repeated winning experience decreases the number of activated (c-fos positive cells in the basolateral amygdala and increases the number of activated cells in the hippocampus; a subsequent no-fight period restores the number of c-fos-positive cells. Our results indicate that extended positive fighting experience in a social conflict heightens aggression, increases proliferation of neuronal progenitors and production of young neurons in the hippocampus, and decreases neuronal activity in the amygdala; these changes can be modified by depriving the winners of the opportunity for further fights.

  9. Dopamine D4 receptor activation increases hippocampal gamma oscillations by enhancing synchronization of fast-spiking interneurons.

    Directory of Open Access Journals (Sweden)

    Richard Andersson

    Full Text Available BACKGROUND: Gamma oscillations are electric activity patterns of the mammalian brain hypothesized to serve attention, sensory perception, working memory and memory encoding. They are disrupted or altered in schizophrenic patients with associated cognitive deficits, which persist in spite of treatment with antipsychotics. Because cognitive symptoms are a core feature of schizophrenia it is relevant to explore signaling pathways that potentially regulate gamma oscillations. Dopamine has been reported to decrease gamma oscillation power via D1-like receptors. Based on the expression pattern of D4 receptors (D4R in hippocampus, and pharmacological effects of D4R ligands in animals, we hypothesize that they are in a position to regulate gamma oscillations as well. METHODOLOGY/PRINCIPAL FINDINGS: To address this hypothesis we use rat hippocampal slices and kainate-induced gamma oscillations. Local field potential recordings as well as intracellular recordings of pyramidal cells, fast-spiking and non-fast-spiking interneurons were carried out. We show that D4R activation with the selective ligand PD168077 increases gamma oscillation power, which can be blocked by the D4R-specific antagonist L745,870 as well as by the antipsychotic drug Clozapine. Pyramidal cells did not exhibit changes in excitatory or inhibitory synaptic current amplitudes, but inhibitory currents became more coherent with the oscillations after application of PD168077. Fast-spiking, but not non-fast spiking, interneurons, increase their action potential phase-coupling and coherence with regard to ongoing gamma oscillations in response to D4R activation. Among several possible mechanisms we found that the NMDA receptor antagonist AP5 also blocks the D4R mediated increase in gamma oscillation power. CONCLUSIONS/SIGNIFICANCE: We conclude that D4R activation affects fast-spiking interneuron synchronization and thereby increases gamma power by an NMDA receptor-dependent mechanism. This

  10. Hippocampal cell proliferation across the day : Increase by running wheel activity, but no effect of sleep and wakefulness

    NARCIS (Netherlands)

    van der Borght, K; Ferrari, F; Klauke, K; Roman, Viktor; Havekes, R; Sgoifo, A; van der Zee, EA; Meerlo, P

    2006-01-01

    The present study investigated whether proliferation of hippocampal progenitors is subject to circadian modulation. Mice were perfused using 3 h intervals throughout the light-dark cycle and brains were stained for Ki-67. Since Ki-67 is not expressed during the G0 phase of the cell cycle, we expecte

  11. The Memory-Impairing Effects of Septal GABA Receptor Activation Involve GABAergic Septo-Hippocampal Projection Neurons

    Science.gov (United States)

    Krebs-Kraft, Desiree L.; Wheeler, Marina G.; Parent, Marise B.

    2007-01-01

    Septal infusions of the [gamma]-aminobutyric acid (GABA)[subscript A] agonist muscimol impair memory, and the effect likely involves the hippocampus. GABA[subscript A] receptors are present on the perikarya of cholinergic and GABAergic septo-hippocampal (SH) projections. The current experiments determined whether GABAergic SH projections are…

  12. Intervention effects of ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of neurotrophin-4 and N-cadherin.

    Directory of Open Access Journals (Sweden)

    Shu-Qiu Wang

    Full Text Available Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS, a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg(2+ free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE. Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i control, ii model (incubated with Mg(2+ free medium for 3 hours, iii GLS group I (incubated with Mg(2+ free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours and iv GLS group II (neurons incubated with Mg(2+ free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours. Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression.

  13. Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

    Directory of Open Access Journals (Sweden)

    Bopanna I Kalappa

    Full Text Available BACKGROUND: The level of expression of functional α7-containing nicotinic acetylcholine receptors (nAChRs in hippocampal CA1 pyramidal neurons is believed to be very low compared to hippocampal CA1 interneurons, and for many years this expression was largely overlooked. However, high densities of expression of functional α7-containing nAChRs in CA1 pyramidal neurons may not be necessary for triggering important cellular and network functions, especially if activation of α7-containing nAChRs occurs in the presence of positive allosteric modulators such as PNU-120596. METHODOLOGY/PRINCIPAL FINDINGS: An approach previously developed for α7-containing nAChRs expressed in tuberomammillary neurons was applied to investigate functional CA1 pyramidal α7-containing nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology. The majority (∼71% of tested CA1 pyramidal neurons expressed low densities of functional α7-containing nAChRs as evidenced by small whole-cell responses to choline, a selective endogenous agonist of α7 nAChRs. These responses were potentiated by PNU-120596, a novel positive allosteric modulator of α7 nAChRs. The density of functional α7-containing nAChRs expressed in CA1 pyramidal neurons (and thus, the normalized net effect of activation, i.e., response net charge per unit of membrane capacitance per unit of time was estimated to be ∼5% of the density observed in CA1 interneurons. The results of this study demonstrate that despite low levels of expression of functional pyramidal α7-containing nAChRs, physiological levels of choline (∼10 µM are sufficient to activate these receptors and transiently depolarize and even excite CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are possible because in the presence of 10 µM choline and 1-5 µM PNU-120596, a single opening of an individual pyramidal α7-containing nAChR ion channel appears to transiently depolarize (∼4 mV the

  14. Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors

    OpenAIRE

    Ivy, Autumn S.; Rex, Christopher S.; Chen, Yuncai; Dubé, Céline; Maras, Pamela M.; Grigoriadis, Dimitri E.; Christine M Gall; Lynch, Gary; Baram, Tallie Z.

    2010-01-01

    Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly ...

  15. Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.

    Directory of Open Access Journals (Sweden)

    Wenjuan Yu

    Full Text Available MK-801, also known as dizocilpine, is a noncompetitive N-methyl-D-aspartic acid (NMDA receptor antagonist that induces schizophrenia-like symptoms. While astrocytes have been implicated in the pathophysiology of psychiatric disorders, including schizophrenia, astrocytic responses to MK-801 and their significance to schizotypic symptoms are unclear. Changes in the expression levels of glial fibrillary acid protein (GFAP, a marker of astrocyte activation in response to a variety of pathogenic stimuli, were examined in the hippocampus of rats treated with the repeated MK-801 injection (0.5 mg/10 ml/kg body weight for 6 days and in primary cultured hippocampal astrocytes incubated with MK-801 (5 or 20 μM for 24 h. Moreover, the expression levels of BDNF and its receptors TrkB and p75 were examined in MK-801-treated astrocyte cultures. MK-801 treatment enhanced GFAP expression in the rat hippocampus and also increased the levels of GFAP protein and mRNA in hippocampal astrocytes in vitro. Treatment of cultured hippocampal astrocytes with MK-801 enhanced protein and mRNA levels of BDNF, TrkB, and p75. Collectively, our results suggest that hippocampal astrocytes may contribute to the pathophysiology of schizophrenia symptoms associated with NMDA receptor hypofunction by reactive transformation and altered BDNF signaling.

  16. α1-Adrenoceptors in the hippocampal dentate gyrus involved in learning-dependent long-term potentiation during active-avoidance learning in rats.

    Science.gov (United States)

    Lv, Jing; Zhan, Su-Yang; Li, Guang-Xie; Wang, Dan; Li, Ying-Shun; Jin, Qing-Hua

    2016-11-01

    The hippocampus is the key structure for learning and memory in mammals and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. The influences of norepinephrine (NE) on the modulation of learning and memory, as well as LTP, through β-adrenoceptors are well documented, whereas the role of α1-adrenoceptors in learning-dependent LTP is not yet clear. In the present study, we measured extracellular concentrations of NE in the hippocampal dentate gyrus (DG) region using an in-vivo brain microdialysis and high-performance liquid chromatography techniques during the acquisition and extinction of active-avoidance behavior in freely moving conscious rats. Next, the effects of prazosin (an antagonist of α1-adrenoceptor) and phenylephrine (an agonist of the α1-adrenoceptor) on amplitudes of field excitatory postsynaptic potential were measured in the DG region during the active-avoidance behavior. Our results showed that the extracellular concentration of NE in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to the baseline level following extinction training. A local microinjection of prazosin into the DG significantly accelerated the acquisition of the active-avoidance behavior, whereas a local microinjection of phenylephrine retarded the acquisition of the active-avoidance behavior. Furthermore, in all groups, the changes in field excitatory postsynaptic potential amplitude were accompanied by corresponding changes in active-avoidance behavior. Our results suggest that NE activation of α1-adrenoceptors in the hippocampal DG inhibits active-avoidance learning by modulation of synaptic efficiency in rats.

  17. Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice.

    Science.gov (United States)

    Majidi, Jafar; Kosari-Nasab, Morteza; Salari, Ali-Akbar

    2016-01-01

    Neonatal infection is associated with increased lifetime risk for neuropsychiatric disorders including anxiety and depression, with evidence showing that dysregulation of the hypothalamic-pituitary-adrenal-(HPA)-axis system may be partly responsible. Preclinical and clinical studies demonstrate that minocycline exhibits antidepressant effects through inhibition of microglial activation and anti-inflammatory actions, and of interest is that recent studies suggest that minocycline alleviates the behavioral abnormalities induced by early-life insults. The current study was designed to determine if developmental minocycline treatment attenuates the neonatal immune activation-induced anxiety- and depression-like symptoms and HPA-axis-dysregulation later in life. To this end, neonatal mice were treated to either lipopolysaccharide or saline on postnatal days (PND) 3-5, then dams during lactation (PND 6-20) and male offspring during adolescence (PND 21-40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1β) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1β in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early

  18. Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice.

    Science.gov (United States)

    Majidi, Jafar; Kosari-Nasab, Morteza; Salari, Ali-Akbar

    2016-01-01

    Neonatal infection is associated with increased lifetime risk for neuropsychiatric disorders including anxiety and depression, with evidence showing that dysregulation of the hypothalamic-pituitary-adrenal-(HPA)-axis system may be partly responsible. Preclinical and clinical studies demonstrate that minocycline exhibits antidepressant effects through inhibition of microglial activation and anti-inflammatory actions, and of interest is that recent studies suggest that minocycline alleviates the behavioral abnormalities induced by early-life insults. The current study was designed to determine if developmental minocycline treatment attenuates the neonatal immune activation-induced anxiety- and depression-like symptoms and HPA-axis-dysregulation later in life. To this end, neonatal mice were treated to either lipopolysaccharide or saline on postnatal days (PND) 3-5, then dams during lactation (PND 6-20) and male offspring during adolescence (PND 21-40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1β) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1β in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early

  19. Effects of coriaria lactone-activated, astrocyte-conditioned medium on estrogen receptor and progesterone receptor expression in rat cortical and hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Jie Rong; Shuhua Zhang

    2009-01-01

    BACKGROUND: Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy.OBJECTIVE: It has been suggested that activated astrocytes alter the expression of the estrogen receptor and progesterone receptor by releasing bioactive substances during epilepsy, thereby affecting neuronal activity in the brain. This study was designed to observe the expression of the estrogen receptor and the progesterone receptor in rat brain following lateral ventricle injection of coriaria lactone-activated, astrocyte-conditioned medium.DESIGN AND SETTING: This immunohistochemical, randomized, controlled, animal study was conducted at the Department of Pathology, Hospital Affiliated to Binzhou Medical College, China.MATERIAL: Coriaria lactone was provided by Huaxi Pharmaceutical Factory, China.METHODS: Forty adult, healthy, male, Sprague Dawley rats were randomly assigned into two groups. Astrocyte-conditioned medium (10 μL) was injected into rat lateral ventricle in the control group (n = 8). Coriaria lactone-activated, astrocyte-conditioned medium (10 μL) was infused into the rat lateral ventricle in the coriaria lactone group (n = 32). At 2, 4, 8 and 12 hours following injection, rats were sacrificed and subjected to immunohistochemistry. Eight rats were studied at each time point.MAIN OUTCOME MEASURES: Behavioral changes were observed in rats of both groups. Expression of the estrogen receptor and the progesterone receptor in rat cortical and hippocampal neurons was measured using immunohistochemistry.RESULTS: Four hours after injection, estrogen receptor levels in rat cortical and hippocampal neurons were significantly higher in the coriaria lactone group than in the control group (P < 0.05). Progesterone receptor levels were significantly lower in the coriaria lactone group than in the control group (P < 0.05). Seizures were not observed in the control group. In the coriaria lactone group, convulsions appeared 30 minutes after injection

  20. Community Service-Learning and Cultural-Historical Activity Theory

    Science.gov (United States)

    Taylor, Alison

    2014-01-01

    This paper explores the potential of cultural-historical activity theory (CHAT), to provide new insights into community service-learning (CSL) in higher education. While CSL literature acknowledges the influences of John Dewey and Paolo Freire, discussion of the potential contribution of cultural-historical activity theory, rooted in the work of…

  1. Brain-Derived Neurotrophic Factor (BDNF) Val66Met Polymorphism Differentially Predicts Hippocampal Function in Medication-Free Patients with Schizophrenia

    Science.gov (United States)

    Eisenberg, Daniel Paul; Ianni, Angela M.; Wei, Shau-Ming; Kohn, Philip D.; Kolachana, Bhaskar; Apud, José; Weinberger, Daniel R.; Berman, Karen F.

    2012-01-01

    A Val66Met single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene impairs activity-dependent BDNF release in cultured hippocampal neurons and predicts impaired memory and exaggerated basal hippocampal activity in healthy humans. Several clinical genetic association studies, along with multi-modal evidence for hippocampal dysfunction in schizophrenia indirectly suggest a relationship between schizophrenia and genetically-determined BDNF function in the hippocampus. To directly test this hypothesized relationship, we studied 47 medication-free patients with schizophrenia or schizoaffective disorder and 74 healthy comparison individuals with genotyping for the Val66Met SNP and [15O]H2O positron emission tomography (PET) to measure resting and working memory-related hippocampal regional cerebral blood flow (rCBF). In patients, harboring a Met allele was associated with significantly less hippocampal rCBF. This finding was opposite to the genotype effect seen in healthy participants, resulting in a significant diagnosis-by-genotype interaction. Exploratory analyses of interregional resting rCBF covariation revealed a specific and significant diagnosis-by-genotype interaction effect on hippocampal-prefrontal coupling. A diagnosis-by-genotype interaction was also found for working-memory related hippocampal rCBF change, which was uniquely attenuated in Met allele-carrying patients. Thus, both task-independent and task-dependent hippocampal neurophysiology accommodates a Met allelic background differently in patients with schizophrenia than in control subjects. Potentially consistent with the hypothesis that cellular sequelae of the BDNF Val66Met SNP interface with aspects of schizophrenic hippocampal and frontotemporal dysfunction, these results warrant future investigation to understand the contributions of unique patient trait or state variables to these robust interactions. PMID:23319002

  2. Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Torgerson Britta M

    2006-01-01

    Full Text Available Abstract Background The presence of the apolipoprotein E (APOE ε4 allele is a major risk factor for the development of Alzheimer's disease (AD, and has been associated with metabolic brain changes several years before the onset of typical AD symptoms. Functional MRI (fMRI is a brain imaging technique that has been used to demonstrate hippocampal activation during measurement of episodic encoding, but the effect of the ε4 allele on hippocampal activation has not been firmly established. Methods The present study examined the effects of APOE genotype on brain activation patterns in the medial temporal lobe (MTL during an episodic encoding task using a well-characterized novel item versus familiar item contrast in cognitively normal, middle-aged (mean = 54 years individuals who had at least one parent with AD. Results We found that ε3/4 heterozygotes displayed reduced activation in the hippocampus and MTL compared to ε3/3 homozygotes. There were no significant differences between the groups in age, education or neuropsychological functioning, suggesting that the altered brain activation seen in ε3/4 heterozygotes was not associated with impaired cognitive function. We also found that participants' ability to encode information on a neuropsychological measure of learning was associated with greater activation in the anterior MTL in the ε3/3 homozygotes, but not in the ε3/4 heterozygotes. Conclusion Together with previous studies reporting reduced glucose metabolism and AD-related neuropathology, this study provides convergent validity for the idea that the MTL exhibits functional decline associated with the APOE ε4 allele. Importantly, these changes were detected in the absence of meaningful neuropsychological differences between the groups. A focus of ongoing work in this laboratory is to determine if these findings are predictive of subsequent cognitive decline.

  3. Inhibition of hippocampal synaptic transmission by impairment of Ral function

    DEFF Research Database (Denmark)

    Owe-Larsson, Björn; Chaves-Olarte, Esteban; Chauhan, Ashok;

    2005-01-01

    Large clostridial cytotoxins and protein overexpression were used to probe for involvement of Ras-related GTPases (guanosine triphosphate) in synaptic transmission in cultured rat hippocampal neurons. The toxins TcdA-10463 (inactivates Rho, Rac, Cdc42, Rap) and TcsL-1522 (inactivates Ral, Rac, Ras......, R-Ras, Rap) both inhibited autaptic responses. In a proportion of the neurons (25%, TcdA-10463; 54%, TcsL-1522), the inhibition was associated with a shift from activity-dependent depression to facilitation, indicating that the synaptic release probability was reduced. Overexpression of a dominant...

  4. A co-culture model of the hippocampal neurogenic niche reveals differential effects of astrocytes, endothelial cells and pericytes on proliferation and differentiation of adult murine precursor cells

    Directory of Open Access Journals (Sweden)

    Fanny Ehret

    2015-11-01

    Full Text Available The niche concept of stem cell biology proposes a functional unit between the precursor cells and their local microenvironment, to which several cell types might contribute by cell–cell contacts, extracellular matrix, and humoral factors. We here established three co-culture models (with cell types separated by membrane for both adherent monolayers and neurospheres to address the potential influence of different niche cell types in the neurogenic zone of the adult hippocampus of mice. Astrocytes and endothelial cells enhanced precursor cell proliferation and neurosphere formation. Endothelial factors also led to a prolonged increase in proliferation after growth factor withdrawal, which otherwise induces differentiation. All niche cell types enhanced cell survival in monolayer cultures, endothelial cells also stimulated neuronal differentiation. A parallel trend elicited by astrocytes did not reach conventional statistical significance. Pericytes had variable effects here. We did not observe changes in differentiation in neurosphere co-cultures. In summary, our data indicate that in precursor cell culture protocols survival could be improved by adding as yet unknown factors physiologically contributed by astrocytes and endothelial cells. Our findings also underscore the complexity of the niche and the differential impact of factors from the different sources on distinct aspects of neuronal development. With the help of the models presented here, identification of these factors and their specific biological activity can now be initiated.

  5. Hippocampal theta oscillations are travelling waves

    OpenAIRE

    Lubenov, Evgueniy V.; Siapas, Athanassios G.

    2009-01-01

    Theta oscillations clock hippocampal activity during awake behaviour and rapid eye movement (REM) sleep. These oscillations are prominent in the local field potential, and they also reflect the subthreshold membrane potential and strongly modulate the spiking of hippocampal neurons. The prevailing view is that theta oscillations are synchronized throughout the hippocampus, despite the lack of conclusive experimental evidence. In contrast, here we show that in freely behaving rats, theta oscil...

  6. 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.

  7. The effects of high-frequency oscillations in hippocampal electrical activities on the classification of epileptiform events using artificial neural networks

    Science.gov (United States)

    Chiu, Alan W. L.; Jahromi, Shokrollah S.; Khosravani, Houman; Carlen, Peter L.; Bardakjian, Berj L.

    2006-03-01

    The existence of hippocampal high-frequency electrical activities (greater than 100 Hz) during the progression of seizure episodes in both human and animal experimental models of epilepsy has been well documented (Bragin A, Engel J, Wilson C L, Fried I and Buzsáki G 1999 Hippocampus 9 137-42 Khosravani H, Pinnegar C R, Mitchell J R, Bardakjian B L, Federico P and Carlen P L 2005 Epilepsia 46 1-10). However, this information has not been studied between successive seizure episodes or utilized in the application of seizure classification. In this study, we examine the dynamical changes of an in vitro low Mg2+ rat hippocampal slice model of epilepsy at different frequency bands using wavelet transforms and artificial neural networks. By dividing the time-frequency spectrum of each seizure-like event (SLE) into frequency bins, we can analyze their burst-to-burst variations within individual SLEs as well as between successive SLE episodes. Wavelet energy and wavelet entropy are estimated for intracellular and extracellular electrical recordings using sufficiently high sampling rates (10 kHz). We demonstrate that the activities of high-frequency oscillations in the 100-400 Hz range increase as the slice approaches SLE onsets and in later episodes of SLEs. Utilizing the time-dependent relationship between different frequency bands, we can achieve frequency-dependent state classification. We demonstrate that activities in the frequency range 100-400 Hz are critical for the accurate classification of the different states of electrographic seizure-like episodes (containing interictal, preictal and ictal states) in brain slices undergoing recurrent spontaneous SLEs. While preictal activities can be classified with an average accuracy of 77.4 ± 6.7% utilizing the frequency spectrum in the range 0-400 Hz, we can also achieve a similar level of accuracy by using a nonlinear relationship between 100-400 Hz and <4 Hz frequency bands only.

  8. Microelectrode array recordings of excitability of low Mg2+-induced acute hippocampal slices

    Institute of Scientific and Technical Information of China (English)

    Fan Yang; Xinwei Gong; Haiqing Gong; Puming Zhang; Peiji Liang; Qinchi LU

    2010-01-01

    Neuronal connections can be detected by neuronal network discharges in hippocampal neurons cultured on multi-electrodes.However,the multi-electrode-array(MEA)has not been widely used in hippocampal slice culture studies focused on epilepsy.The present study induced spontaneous synchronous epileptiform activity using low Mg2+artificial cerebrospinal fluid on acute hippocampal slices to record hippocampal discharges with MEA.Results showed that burst duration and average number of spikes in a burst were significantly greater in the CA3 compared with dentate gyrus and CA1 areas.In Schaffer cut-off group,CA1 area discharges disappeared,but synchronous discharges remained in the CA3 area.Moreover,synchronous discharge frequency in the Schaffer cut-off group was similar to control.However,burst duration and average number of spikes in a burst were significantly decreased compared with control(P < 0.05).Results demonstrated that highest neuronal excitability occurred in the CA3 area,and synchronous discharges induced by low Mg2+originated from the CA3 region.

  9. Prefrontal and Hippocampal Brain Volume Deficits: The Role of Low Physical Activity on Brain Plasticity in First-Episode Schizophrenia Patients

    Science.gov (United States)

    McEwen, Sarah C.; Hardy, Anthony; Ellingson, Benjamin M.; Jarrahi, Behnaz; Sandu, Navjot; Subotnik, Kenneth L.; Ventura, Joseph; Nuechterlein, Keith H.

    2015-01-01

    Objective Our objective in the present study was to conduct the first empirical study to examine regular physical activity habits and their relationship with brain volume and cortical thickness in patients in the early phase of schizophrenia. Relationships between larger brain volumes and higher physical activity levels have been reported in samples of healthy and aging populations, but have never been explored in first-episode schizophrenia patients. Method We collected MRI structural scans in fourteen first-episode schizophrenia patients with either self-reported low or high physical activity levels. Results We found a reduction in total grey matter volume, prefrontal cortex (PFC) and hippocampal grey matter volumes in the low physical activity group compared to the high activity group. Cortical thickness in the dorsolateral and orbitofrontal PFC were also significantly reduced in the low physical activity group compared to the high activity group. In the combined sample, greater overall physical activity levels showed a non-significant tendency with better performance on tests of verbal memory and social cognition. Conclusions Together these pilot study findings suggest that greater amounts of physical activity may have a positive influence on brain health and cognition in first-episode schizophrenia patients and support the development of physical exercise interventions in this patient population to improve brain plasticity and cognitive functioning. PMID:26581798

  10. Safety Cultures in Water-Based Outdoor Activities in Denmark

    DEFF Research Database (Denmark)

    Andkjær, Søren; Arvidsen, Jan

    2015-01-01

    In this paper, we report on the study Safe in Nature (Tryg i naturen) in which the aim was to analyze and discuss risk and safety related to outdoor recreation in the coastal regions of Denmark. A cultural perspective is applied to risk management and the safety cultures related to three selected...... water-based outdoor activities: small boat fishing, sea kayaking, and kite surfing. The theoretical framework used was cultural analysis and the methodological approach was mixed methods using case studies with survey and qualitative interviews. The study indicates that safety is a complex matter...... and that safety culture can be understood as the sum and interaction among six categories. The safety culture is closely related to the activity and differs widely among activities. We suggest a broad perspective be taken on risk management wherein risk and safety can be managed at different levels. Small boat...

  11. CULTURAL HISTORICAL ACTIVITY THEORY: EXPLORING PRINCIPALS’ INSTRUCTIONAL LEADERSHIP

    Directory of Open Access Journals (Sweden)

    Fulya Damla Kentli

    2016-09-01

    Full Text Available Instructional leadership activities are significant for school development. Although many researchers in this field consider leadership activities relating to the work of school principals, in effect, leadership is a network activity that includes all school staff. This study aims to show this interdependence network activity within Cultural Historical Activity Theory. The research question is “what are the activities of an instructional leader?” in order to understand instructional leadership activities in school from perspectives of Turkish graduate students and Cultural Historical Activity Theory. The answers are conceptualized within the framework of an Activity Theory. The students were asked to write about the activities of an instructional leader in the first and last course of the semester. Eighteen graduate students participated in this study.

  12. Differential activation and tyrosine hydroxylase distribution in the hippocampal, pallial and midbrain brain regions in response to cognitive performance in Indian house crows exposed to abrupt light environment.

    Science.gov (United States)

    Taufique, S K Tahajjul; Kumar, Vinod

    2016-11-01

    Disruption of the cyclic feature of the day-night environment can cause negative effects on daily activity and advanced brain functions such as learning, memory and decision-making behaviour. These functions in songbirds, including corvids, involve the hippocampus, pallium and midbrain, as revealed by ZENK (a neuronal activation marker) and tyrosine hydroxylase (TH) expressions. TH is rate-limiting marker enzyme of the biosynthesis of dopamine, widely implicated in learning and memory. Here, we measured ZENK and TH immunoreactivity in the hippocampal, pallial and midbrain regions in response to cognitive performance (learning-memory retrieval) tests in Indian house crows (Corvus splendens) exposed to constant light environment (LL) with controls on 12h light:12h darkness. Along with the decay of circadian rhythm in activity behaviour, LL caused a significant decline in the cognitive performance. There was also a decrease under LL in the activity of neurons in the hippocampus, medial and central caudal nidopallium, and hyperpallium apicale, which are widely distributed with TH-immunoreactive fibres. Further, under LL, TH- immunoreactive neurons were reduced in number in midbrain dopamine synthesis sites, the venteral tegmental area (VTA) and substantia nigra (SN), with a negative correlation of co-localized ZENK/TH- immunoreactive cells on errors during the association tasks. These results show decreased activity of learning and memory neural systems, and underscore the role of dopamine in reduced cognitive performance of diurnal corvids with disrupted circadian rhythms under an abrupt light environment. PMID:27478138

  13. Spatial tuning and brain state account for dorsal hippocampal CA1 activity in a non-spatial learning task

    Science.gov (United States)

    Shan, Kevin Q; Lubenov, Evgueniy V; Papadopoulou, Maria; Siapas, Athanassios G

    2016-01-01

    The hippocampus is a brain area crucial for episodic memory in humans. In contrast, studies in rodents have highlighted its role in spatial learning, supported by the discovery of place cells. Efforts to reconcile these views have found neurons in the rodent hippocampus that respond to non-spatial events but have not unequivocally dissociated the spatial and non-spatial influences on these cells. To disentangle these influences, we trained freely moving rats in trace eyeblink conditioning, a hippocampally dependent task in which the animal learns to blink in response to a tone. We show that dorsal CA1 pyramidal neurons are all place cells, and do not respond to the tone when the animal is moving. When the animal is inactive, the apparent tone-evoked responses reflect an arousal-mediated resumption of place-specific firing. These results suggest that one of the main output stages of the hippocampus transmits only spatial information, even in this non-spatial task. DOI: http://dx.doi.org/10.7554/eLife.14321.001 PMID:27487561

  14. Enhancing cultural awareness education for undergraduate medical students: Initial findings from a unique cultural immersion activity

    Directory of Open Access Journals (Sweden)

    Sally Sargeant

    2016-07-01

    Full Text Available Background Cultural awareness education is mandatory for medical programs, with particular emphasis on Aboriginal and Torres Strait Islander health. However, there is limited evidence to measure the impact of such education has on medical students. Aims This paper presents the development and delivery of a cultural immersion activity for first year undergraduate medical students. Additionally we explore how this type of activity may improve attitudes, comprehension and perceived competence relating to working with and understanding people of different cultures. Methods A pre- and post-survey design was utilised in connection with a cultural immersion activity. First year medical students (N=284, responses 196, 69 per cent from three cohorts (2012–2014 inclusive voluntarily completed a cultural awareness questionnaire, which contained items that related to perceptions, personal characteristics and educational competence. The main outcome measures were changes in perceived cultural knowledge, awareness, beliefs and attitudes. Data were analysed using principal component analysis and obtained means comparison. Results Principal component analysis revealed five dimensions for pre-post comparison: Knowledge Acquisition, Perceptions of Role Modelling, Internal Beliefs and Reflections, Personality Variables and Institutional Influences. Non-parametric means comparison showed increased ratings for knowledge acquisition and institutional influences (p<0.001, whilst a decline was noted for the personality variables (p<0.05. Conclusion Cultural immersion has great potential to elicit positive shifts in attitudinal and knowledge related aspects of cultural awareness at early stages in medical curricula. Negative directions also suggest that students question their beliefs and behaviours relating to cultural knowledge.

  15. Smabarnens Kultur-Och Mediebarometer. (Barometer of Children's Cultural Activity).

    Science.gov (United States)

    Filipson, Leni; Schyller, Ingela

    This is the first of a planned series of investigations of the media habits and other cultural activities of 3- to 8-year-old Swedish children. Diagrams show the percent of children who use the various media on an average day and the frequency of their participation in such activities as visits to the theater, museum, or library. The amount of…

  16. Changes In Growth Culture FDA Activity Under Changing Growth Conditions

    DEFF Research Database (Denmark)

    Jørgensen, Per Elberg; Eriksen, Thomas Juul; Jensen, Bjørn K.

    1992-01-01

    of the bacteria. The FDA activity/ATP ratio was calculated for different concentrations of autoclaved sludge. A faster decay rate of ATP relative to FDA hydrolysis activity was observed, thus causing changes in the ratio. Furthermore, comparison between values obtained from pure cultures and different soils...

  17. Empathy in hippocampal amnesia.

    Science.gov (United States)

    Beadle, J N; Tranel, D; Cohen, N J; Duff, M C

    2013-01-01

    Empathy is critical to the quality of our relationships with others and plays an important role in life satisfaction and well-being. The scientific investigation of empathy has focused on characterizing its cognitive and neural substrates, and has pointed to the importance of a network of brain regions involved in emotional experience and perspective taking (e.g., ventromedial prefrontal cortex, amygdala, anterior insula, cingulate). While the hippocampus has rarely been the focus of empathy research, the hallmark properties of the hippocampal declarative memory system (e.g., representational flexibility, relational binding, on-line processing capacity) make it well-suited to meet some of the crucial demands of empathy, and a careful investigation of this possibility could make a significant contribution to the neuroscientific understanding of empathy. The present study is a preliminary investigation of the role of the hippocampal declarative memory system in empathy. Participants were three patients (1 female) with focal, bilateral hippocampal (HC) damage and severe declarative memory impairments and three healthy demographically matched comparison participants. Empathy was measured as a trait through a battery of gold standard questionnaires and through on-line ratings and prosocial behavior in response to a series of empathy inductions. Patients with hippocampal amnesia reported lower cognitive and emotional trait empathy than healthy comparison participants. Unlike healthy comparison participants, in response to the empathy inductions hippocampal patients reported no increase in empathy ratings or prosocial behavior. The results provide preliminary evidence for a role for hippocampal declarative memory in empathy.

  18. Empathy in Hippocampal Amnesia

    Science.gov (United States)

    Beadle, J. N.; Tranel, D.; Cohen, N. J.; Duff, M. C.

    2013-01-01

    Empathy is critical to the quality of our relationships with others and plays an important role in life satisfaction and well-being. The scientific investigation of empathy has focused on characterizing its cognitive and neural substrates, and has pointed to the importance of a network of brain regions involved in emotional experience and perspective taking (e.g., ventromedial prefrontal cortex, amygdala, anterior insula, cingulate). While the hippocampus has rarely been the focus of empathy research, the hallmark properties of the hippocampal declarative memory system (e.g., representational flexibility, relational binding, on-line processing capacity) make it well-suited to meet some of the crucial demands of empathy, and a careful investigation of this possibility could make a significant contribution to the neuroscientific understanding of empathy. The present study is a preliminary investigation of the role of the hippocampal declarative memory system in empathy. Participants were three patients (1 female) with focal, bilateral hippocampal (HC) damage and severe declarative memory impairments and three healthy demographically matched comparison participants. Empathy was measured as a trait through a battery of gold standard questionnaires and through on-line ratings and prosocial behavior in response to a series of empathy inductions. Patients with hippocampal amnesia reported lower cognitive and emotional trait empathy than healthy comparison participants. Unlike healthy comparison participants, in response to the empathy inductions hippocampal patients reported no increase in empathy ratings or prosocial behavior. The results provide preliminary evidence for a role for hippocampal declarative memory in empathy. PMID:23526601

  19. Role of Toll-like receptor 4 in inflammatory reactions of hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Yae Hu; Jiahui Mao; Yu Zhang; Ailing Zhou

    2013-01-01

    Lipopolysaccharide stimulates Toll-like receptor 4 on immune cells to produce immune mediators. Toll-like receptor 4 is also expressed by non-immune cells, which can be stimulated by lipopolysaccharide. However, whether Toll-like receptor 4 is expressed by primary cultured hippocampal neurons and its specific role in lipopolysaccharide-induced neuroinflammation is currently undefined. In this study, Toll-like receptor 4 antibody blocking was used to analyze the Toll-like receptor 4 signaling pathway and changes in inflammation of lipopolysaccharide stimulated hippocampal neurons. Immunofluorescence showed that Toll-like receptor 4 protein was mainly located in the membrane of hippocampal neurons. Quantitative reverse transcription-PCR and western blot assay showed that after stimulation of lipopolysaccharide, the mRNA and protein levels of Toll-like receptor 4 and the mRNA levels of interleukin-1β and tumor necrosis factor-α were significantly increased. In addition, there was increased phosphorylation and degradation of kappa B α inhibitor in the cytosol and increased nuclear factor-κB p65 expression in the nuclei. Pretreatment with Toll-like receptor 4 antibody could almost completely block this increase. These experimental findings indicate that lipopolysaccharide participates in neuroinflammation by stimulating Toll-like receptor 4/nuclear factor-κB pathway in hippocampal neurons, which may be both "passive victims" and "activators" of neuroinflammation.

  20. Ethanol impairs muscarinic receptor-induced neuritogenesis in rat hippocampal slices: Role of astrocytes and extracellular matrix proteins.

    Science.gov (United States)

    Giordano, Gennaro; Guizzetti, Marina; Dao, Khoi; Mattison, Hayley A; Costa, Lucio G

    2011-12-01

    In an in vitro co-culture system of astrocytes and neurons, stimulation of cholinergic muscarinic receptors in astrocytes had been shown to cause neuritogenesis in hippocampal neurons, and this effect was inhibited by ethanol. The present study sought to confirm these earlier findings in a more complex system, in vitro rat hippocampal slices in culture. Exposure of hippocampal slices to the cholinergic agonist carbachol (1mM for 24h) induced neurite outgrowth in hippocampal pyramidal neurons, which was mediated by activation of muscarinic M3 receptors. Specifically, carbachol induced a >4-fold increase in the length of the longest neurite, and a 4-fold increase in the length of minor neurites and in the number of branches. Co-incubation of carbachol with ethanol (50mM) resulted in significant inhibition of the effects induced by carbachol on all parameters measured. Neurite outgrowth in CNS neurons is dependent on various permissive factors that are produced and released by glial cells. In hippocampal slices carbachol increased the levels of two extracellular matrix protein, fibronectin and laminin-1, by 1.6-fold, as measured by Western blot. Co-incubation of carbachol with ethanol significantly inhibited these increases. Carbachol-induced increases in levels of extracellular matrix proteins were antagonized by a M3 muscarinic receptor antagonist. Furthermore, function-blocking fibronectin or laminin-1 antibodies antagonized the effect of carbachol on neurite outgrowth. These results indicate that in hippocampal slices stimulation of muscarinic M3 receptors induces neurite outgrowth, which is mediated by fibronectin and laminin-1, two extracellular matrix proteins released by astrocytes. By decreasing fibronectin and laminin levels ethanol prevents carbachol-induced neuritogenesis. These findings highlight the importance of glial-neuronal interactions as important targets in the developmental neurotoxicity of alcohol.

  1. Effects of L-3-n-butylphthalide on caspase-3 and nuclear factor kappa-B expression in primary basal forebrain and hippocampal cultures after beta-amyloid peptide 1-42 treatment

    Institute of Scientific and Technical Information of China (English)

    Ruixia Wang; Yong Zhang; Liangliang Jiang; Guozhao Ma; Qingxi Fu; Jialong Li; Peng Yan; Lunqian Shen; Yabo Feng; Chunxia Li; Zaiying Pang; Yuanxiao Cui; Chunfu Chen; Yifeng Du; Zhaokong Liu

    2009-01-01

    BACKGROUND: L-3-n-butylphthalide (L-NBP) can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 (Aβ1-42).OBJECTIVE: To observe the neuroprotective effects of L-NBP on caspase-3 and nuclear factor kappa-B (NF-кB) expression in a rat model of Alzheimer's disease.DESIGN, TIME AND SETTING: A cell experiment was performed at the Central Laboratory of Provincial Hospital affiliated to Shandong University between January 2008 and August 2008.MATERIALS: L-NBP (purity>98%) was provided by Shijiazhuang Pharma Group NBP Pharmaceutical Company Limited. Aβ1-42, 3-[4,5-dimethylthiazolo-2]-2,5 iphenyltetrazolium bromide (MTT), and rabbit anti-Caspase-3 polyclonal antibody were provided by Cell Signaling, METHODS: Primary cultures were generated from rat basal forebrain and hippocampal neurons at 17 or 19 days of gestation. The cells were assigned into five groups: the control group, the Aβ1-42 group (2μmol/L), the Aβ1-42+0.1μmol/L L-NBP group, the Aβ1-42+1 μmol/L L-NBP group, and the Aβ1-42 + 10μmol/L L-NBP group. The neurons were treated with Aβ1-42 (2 μmol/L) alone or in combination with L-NBP (0.1, 1, 10μmol/L) for 48 hours. Cells in the control group were incubated in PBS.MAIN OUTCOME MEASURES: Morphologic changes were evaluated using inverted microscopy, Western blot.RESULTS: Induction with Aβ1-42 for 48 hours caused cell death and soma atrophy, and increased the high dose (P<0.05).CONCLUSION: Aβ1-42 is toxic to basal forebrain and hippocampal primary neurons; L-NBP protects against this toxicity and inhibits the induction of caspase-3 and NF-κB expression.

  2. Activation of the dorsal hippocampal nicotinic acetylcholine receptors improves tamoxifen-induced memory retrieval impairment in adult female rats.

    Science.gov (United States)

    Tajik, Azam; Rezayof, Ameneh; Ghasemzadeh, Zahra; Sardari, Maryam

    2016-07-01

    Tamoxifen (TAM), a selective estrogen receptor modulator, has frequently been used in the treatment of breast cancer. In view of the fact that cognitive deficits in women who receive adjuvant chemotherapy for breast cancer is a common health problem, using female animal models for investigating the cognitive effects of TAM administration may improve our knowledge of TAM therapy. Therefore, the present study assessed the role of dorsal hippocampal cholinergic nicotinic receptors (nAChRs) in the effect of TAM administration on memory retrieval in ovariectomized (OVX) and non-OVX female rats using a passive avoidance learning task. Our results showed that pre-test administration of TAM (2-6mg/kg) impaired memory retrieval. Pre-test intra-CA1 microinjection of nicotine (0.3-0.5μg/rat) reversed TAM-induced memory impairment. Pre-test intra-CA1 microinjection of mecamylamine (0.1-0.3μg/rat) plus 2mg/kg (an ineffective dose) of TAM impaired memory retrieval. Pre-test intra-CA1 microinjection of the same doses of nicotine and mecamylamine by themselves had no effect on memory retrieval. In OVX rats, the administration of TAM (6mg/kg) produced memory impairment but pre-test intra-CA1 microinjection of nicotine (0.5μg/rat) had no effect on TAM response. Moreover, the administration of an ineffective dose of TAM (2mg/kg) had no effect on memory retrieval in OVX rats, while pre-test intra-CA1 microinjection of mecamylamine (0.3μg/rat) impaired memory retrieval. Taken together, it can be concluded that the impairing effect of TAM on memory formation may be modulated by nAChRs of the CA1 regions. It seems that memory impairment may be considered as an important side effect of TAM. PMID:27072849

  3. Taurine increases hippocampal neurogenesis in aging mice

    Directory of Open Access Journals (Sweden)

    Elias Gebara

    2015-05-01

    Full Text Available Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.

  4. MicroRNA-124 and -137 cooperativity controls caspase-3 activity through BCL2L13 in hippocampal neural stem cells

    NARCIS (Netherlands)

    M. Schouten; S.A. Fratantoni; C.J. Hubens; S.R. Piersma; T.V. Pham; P. Bielefeld; R.A. Voskuyl; P.J. Lucassen; C.R. Jimenez; C.P. Fitzsimons

    2015-01-01

    Adult neurogenesis continuously contributes new neurons to hippocampal circuits and the programmed death of a subset of immature cells provides a primary mechanism controlling this contribution. Epileptic seizures induce strong structural changes in the hippocampus, including the induction of adult

  5. Effects of Arc/Arg3.1 gene deletion on rhythmic synchronization of hippocampal CA1 neurons during locomotor activity and sleep.

    Science.gov (United States)

    Malkki, Hemi A I; Mertens, Paul E C; Lankelma, Jan V; Vinck, Martin; van Schalkwijk, Frank J; van Mourik-Donga, Laura B; Battaglia, Francesco P; Mahlke, Claudia; Kuhl, Dietmar; Pennartz, Cyriel M A

    2016-05-01

    The activity-regulated cytoskeletal-associated protein/activity regulated gene (Arc/Arg3.1) is crucial for long-term synaptic plasticity and memory formation. However, the neurophysiological substrates of memory deficits occurring in the absence of Arc/Arg3.1 are unknown. We compared hippocampal CA1 single-unit and local field potential (LFP) activity in Arc/Arg3.1 knockout and wild-type mice during track running and flanking sleep periods. Locomotor activity, basic firing and spatial coding properties of CA1 cells in knockout mice were not different from wild-type mice. During active behavior, however, knockout animals showed a significantly shifted balance in LFP power, with a relative loss in high-frequency (beta-2 and gamma) bands compared to low-frequency bands. Moreover, during track-running, knockout mice showed a decrease in phase locking of spiking activity to LFP oscillations in theta, beta and gamma bands. Sleep architecture in knockout mice was not grossly abnormal. Sharp-wave ripples, which have been associated with memory consolidation and replay, showed only minor differences in dynamics and amplitude. Altogether, these findings suggest that Arc/Arg3.1 effects on memory formation are not only manifested at the level of molecular pathways regulating synaptic plasticity, but also at the systems level. The disrupted power balance in theta, beta and gamma rhythmicity and concomitant loss of spike-field phase locking may affect memory encoding during initial storage and memory consolidation stages. PMID:27038743

  6. Astragaloside Ⅳ inhibits spontaneous synaptic transmission and synchronized Ca2+ oscillations on hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Shao-qing ZHU; Lei QI; Yan-fang RUI; Ru-xin LI; Xiang-ping HE; Zuo-ping XIE

    2008-01-01

    Aim: To investigate the changes in the spontaneous neuronal excitability in-duced by astragaloside Ⅳ (AGS-Ⅳ) in the cultured hippocampal network. Methods: Hippocampal neurons in culture for 9-11 d were used for this study. The sponta-neous synaptic activities of these hippocampal neurons were examined by Ca2+ imaging and whole-cell patch-clamp techniques. In total, 40 mg/L AGS-Ⅳ dis-solved in DMSO and 2 mL/L DMSO were applied to the neurons under a micro-scope while the experiments were taking place. Results: AGS-Ⅳ inhibited the frequencies of synchronized spontaneous Ca2+ oscillations to 59.39%+3.25% (mean+SEM), the spontaneous postsynaptic currents to 43.78%±7.72% (mean±SEM), and the spontaneous excitatory postsynaptic currents to 49.25%±7.06% (mean±SEM) of those of the control periods, respectively, at 16 min after the AGS-Ⅳ applications. AGS-Ⅳ also decreased the peak values of the voltage-gated K+ and Na+ channel currents at that time point. Conclusion: These results indicate that AGS-Ⅳ suppresses the spontaneous neuronal excitabilities effectively. Such a modulation of neuronal activity could represent new evidence for AGS-Ⅳ as a neuroprotector.

  7. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...... and in established cell lines was reduced to about the same basic level after treatment with heparin, a highly specific inhibitor of CKII activity. The activity of the cAMP-dependent protein kinase was virtually the same in fibroblasts and various human tumour cell lines investigated....

  8. Developmental changes in hippocampal associative coding.

    Science.gov (United States)

    Goldsberry, Mary E; Kim, Jangjin; Freeman, John H

    2015-03-11

    Behavioral analyses of the ontogeny of memory have shown that hippocampus-dependent learning emerges relatively late in postnatal development compared with simple associative learning. Maturation of hippocampal mnemonic mechanisms has been hypothesized to underlie the development of the later emerging learning processes. However, the role of hippocampal maturation in learning has not been examined directly. The goal of the present study was to examine developmental changes in hippocampal neuronal coding during acquisition of a hippocampus-dependent learning task. We recorded activity from CA1 pyramidal cells in rat pups while they were trained on trace eyeblink conditioning. Trace eyeblink conditioning is a Pavlovian conditioning task that involves the association of a conditioned stimulus (CS) with an unconditioned stimulus over a stimulus-free trace interval. The inclusion of the trace interval is what makes the task hippocampus dependent. In the present study, rats were trained at 21-23, 24-26, and 31-33 d of age. Previous research from our laboratory and others shows that trace conditioning begins to emerge during the third postnatal week. The results indicate that hippocampal neurons show a substantial increase in responsiveness to task-relevant events during development. Moreover, there is an age-related increase in the proportion of neurons that respond to a combination of trial events (e.g., CS and trace). Our findings indicate that the developmental emergence of hippocampally mediated learning is related to increases in the strength and complexity of CA1 associative coding.

  9. Activation of the canonical nuclear factor-κB pathway is involved in isoflurane-induced hippocampal interleukin-1β elevation and the resultant cognitive deficits in aged rats

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zheng-Qian; Rong, Xiao-Ying; Liu, Ya-Jie; Ni, Cheng [Department of Anesthesiology, Peking University Third Hospital, Beijing 100191 (China); Tian, Xiao-Sheng [Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Peking University Health Science Center, Beijing 100191 (China); Mo, Na [Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021 (China); Chui, De-Hua, E-mail: dchui@bjmu.edu.cn [Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Peking University Health Science Center, Beijing 100191 (China); Guo, Xiang-Yang, E-mail: puthmzk@163.com [Department of Anesthesiology, Peking University Third Hospital, Beijing 100191 (China)

    2013-09-06

    Highlights: •Isoflurane induces hippocampal IL-1β elevation and cognitive deficits in aged rats. •Isoflurane transiently activates the canonical NF-κB pathway in aged rat hippocampus. •NF-κB inhibitor mitigates isoflurane-induced IL-1β elevation and cognitive deficits. •We report a linkage between NF-κB signaling, IL-1β expression, and cognitive changes. -- Abstract: Although much recent evidence has demonstrated that neuroinflammation contributes to volatile anesthetic-induced cognitive deficits, there are few existing mechanistic explanations for this inflammatory process. This study was conducted to investigate the effects of the volatile anesthetic isoflurane on canonical nuclear factor (NF)-κB signaling, and to explore its association with hippocampal interleukin (IL)-1β levels and anesthetic-related cognitive changes in aged rats. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in IκB kinase and IκB phosphorylation, as well as a reduction in the NF-κB inhibitory protein (IκBα), were observed in the hippocampi of isoflurane-exposed rats compared with control rats. These events were accompanied by an increase in NF-κB p65 nuclear translocation at 6 h after isoflurane exposure and hippocampal IL-1β elevation from 1 to 6 h after isoflurane exposure. Nevertheless, no significant neuroglia activation was observed. Pharmacological inhibition of NF-κB activation by pyrrolidine dithiocarbamate markedly suppressed the IL-1β increase and NF-κB signaling, and also mitigated the severity of cognitive deficits in the Morris water maze task. Overall, our results demonstrate that isoflurane-induced cognitive deficits may stem from upregulation of hippocampal IL-1β, partially via activation of the canonical NF-κB pathway, in aged rats.

  10. High-frequency magnetic stimulation attenuates beta-amyloid protein 1-42 neurotoxicity in organotypic hippocampal slices

    Institute of Scientific and Technical Information of China (English)

    Don-Kyu Kim; Young Chul Yoon; Soo Ahn Chae; Kyung Mook Seo; Tai Ryoon Han; Si-Hyun Kang

    2010-01-01

    Repetitive transcranial magnetic stimulation(rTMS)has been utilized as a therapeutic tool for neurodegenerative disorders including Alzheimer's disease.However,the precise mechanisms of its clinical effects remain unknown.β-amyloid(Aβ)exhibits direct neurotoxic effects and is closely related to neuronal degeneration in Alzheimer's disease.Therefore,it has been hypothesized that the neuroprotective effects of rTMS are related to the mechanisms of protection against Aβneurotoxicity.Organotypic hippocampal slices were prepared from 8-day old,Sprague Dawley rats.The tissue slices were exposed to 100 μmol/L Aβ1-42 since day 12 in vitro with and without high-frequency(20 Hz)magnetic stimulation.Magnetic stimulation efficacy was evaluated by measuring neuronal nuclei(NeuN)protein expression and by observing cultures following propidium iodide fluorescence staining and bromodeoxyuridine(BrdU)immunohistochemistry.Lactate dehydrogenase activity was detected in the culture media to evaluate hippocampal neuronal damage.Our results demonstrated that high-frequency magnetic stimulation significantly reversed the reduction of NeuN protein expression because of Aβ1-42 exposure(P < 0.05)and significantly reduced the number of damaged cells in the hippocampal slices(P < 0.05).However,lactate dehydrogenase levels and anti-BrdU staining results did not reveal any statistical differences.These findings indicate that high-frequency magnetic stimulation might have protective effect on hippocampal neurons from Aβ1-42 neurotoxicity.

  11. Multisite electrophysiological recordings by self-assembled loose-patch-like junctions between cultured hippocampal neurons and mushroom-shaped microelectrodes

    Science.gov (United States)

    Shmoel, Nava; Rabieh, Noha; Ojovan, Silviya M.; Erez, Hadas; Maydan, Eilon; Spira, Micha E.

    2016-01-01

    Substrate integrated planar microelectrode arrays is the “gold standard” method for millisecond-resolution, long-term, large-scale, cell-noninvasive electrophysiological recordings from mammalian neuronal networks. Nevertheless, these devices suffer from drawbacks that are solved by spike-detecting, spike-sorting and signal-averaging techniques which rely on estimated parameters that require user supervision to correct errors, merge clusters and remove outliers. Here we show that primary rat hippocampal neurons grown on micrometer sized gold mushroom-shaped microelectrodes (gMμE) functionalized simply by poly-ethylene-imine/laminin undergo self-assembly processes to form loose patch-like hybrid structures. More than 90% of the hybrids formed in this way record monophasic positive action potentials (APs). Of these, 34.5% record APs with amplitudes above 300 μV and up to 5,085 μV. This self-assembled neuron-gMμE configuration improves the recording quality as compared to planar MEA. This study characterizes and analyzes the electrophysiological signaling repertoire generated by the neurons-gMμE configuration, and discusses prospects to further improve the technology. PMID:27256971

  12. Hippocampal activation of c-Jun N-terminal kinase,protein kinase B,and p38 mitogen-activated protein kinase in a chronic stress rat model of depression

    Institute of Scientific and Technical Information of China (English)

    Wei Dai; Weidong Li; Jun Lu; Yingge A; Ya Tu

    2010-01-01

    Recent studies have shown that vaned stress stimuli activate c-Jun N-terminal kinase(JNK),protein kinase B(Akt),and p38 mitogen-activated protein kinase(p38)signal transduction pathway,and also regulate various apoptotic cascades.JNK and p38 promote apoptosis,but Akt protects against apoptosis,in hippocampal neurons.However,changes in the transduction pathway in different regions of brain tissues in a chronic stress rat model of depression remain poorly understood.Results from this study showed that JNK phosphorylation levels were significantly greater in the stress group hippocampus compared with the control group(P 0.05).These results suggested that the JNK signal pathway is activated by JNK phosphorylation and participates in pathophysiological changes in rat models of depression.

  13. Activity patterns of cultured neural networks on micro electrode arrays

    NARCIS (Netherlands)

    Rutten, W.L.C.; Pelt, van J.

    2001-01-01

    A hybrid neuro-electronic interface is a cell-cultured micro electrode array, acting as a neural information transducer for stimulation and/or recording of neural activity in the brain or the spinal cord (ventral motor region or dorsal sensory region). It consists of an array of micro electrodes on

  14. Media Literacy Art Education: Logos, Culture Jamming, and Activism

    Science.gov (United States)

    Chung, Sheng Kuan; Kirby, Michael S.

    2009-01-01

    Critical media literacy art education teaches students to: (1) appreciate the aesthetic qualities of media; (2) critically negotiate meanings and analyze media culture as products of social struggle; and (3) use media technologies as instruments of creative expression and social activism. In concert with art education practices oriented toward…

  15. "Vygotsky's Neglected Legacy": Cultural-Historical Activity Theory

    Science.gov (United States)

    Roth, Wolff-Michael; Lee, Yew-Jin

    2007-01-01

    The authors describe an evolving theoretical framework that has been called one of the best kept secrets of academia: cultural-historical activity theory, the result of proposals Lev Vygotsky first articulated but that his students and followers substantially developed to constitute much expanded forms in its second and third generations. Besides…

  16. ClC-3 chloride channel in hippocampal neuronal apoptosis

    Institute of Scientific and Technical Information of China (English)

    Lijuan Xu; Shuling Zhang; Hongling Fan; Zhichao Zhong; Xi Li; Xiaoxiao Jin; Quanzhong Chang

    2013-01-01

    Over-production of nitric oxide is pathogenic for neuronal apoptosis around the ischemic area fol-lowing ischemic brain injury. In this study, an apoptotic model in rat hippocampal neurons was tablished by 0.5 mmol/L 3-morpholinosyndnomine (SIN-1), a nitric oxide donor. The models were then cultured with 0.1 mmol/L of 4,4’-di sothiocyanostilbene-2,2’-disulfonic acid (DIDS;the chloride channel blocker) for 18 hours. Neuronal survival was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was assayed by Hoechst 33342-labeled neuronal DNA fluorescence staining. Western blot analysis and immunoche-nescence staining were applied to determine the changes of activated caspase-3 and CIC-3 channel proteins. Real-time PCR was used to detect the mRNA expression of CIC-3. The results showed that SIN-1 reduced the neuronal survival rate, induced neuronal apoptosis, and promoted ClC-3 chloride channel protein and mRNA expression in the apoptotic neurons. DIDS reversed the effect of SIN-1. Our findings indicate that the increased activities of the ClC-3 chloride channel may be involved in hippocampal neuronal apoptosis induced by nitric oxide.

  17. Empathy in hippocampal amnesia

    Directory of Open Access Journals (Sweden)

    Janelle N Beadle

    2013-03-01

    Full Text Available The scientific investigation of empathy has become a cornerstone in the field of social cognition. Empathy is critical to the quality of our relationships with others and plays an important role in life satisfaction and well-being. Scientific investigations of empathy have focused on characterizing its cognitive and neural substrates, pointing to a network of brain regions involved in emotional experience and perspective taking (e.g., ventromedial prefrontal cortex, amygdala, anterior insula, cingulate. While the hippocampus has rarely been the focus of empathy research, we propose that there are compelling reasons to inquire about the contribution of the hippocampus to social cognition. We propose that the hallmark properties of the hippocampal declarative memory system (e.g., representational flexibility, relational binding, on-line processing capacity make it well-suited to meet the demands of empathy. The present study is a preliminary investigation of the role of the hippocampal declarative memory system in empathy. Participants were three patients (1 female with focal, bilateral hippocampal (HC damage and severe declarative memory impairments and three healthy demographically matched comparison participants. Empathy was measured as a trait through a battery of gold standard questionnaires and through on-line ratings and prosocial behavior in response to a series of empathy inductions. Patients with hippocampal amnesia reported lower cognitive and emotional trait empathy than healthy comparison participants. In response to the empathy inductions, unlike healthy comparison participants, hippocampal patients reported no increase in empathy ratings or prosocial behavior from the control condition. Taken together, these results provide preliminary evidence for a role of hippocampal declarative memory in empathy.

  18. Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.

    Directory of Open Access Journals (Sweden)

    Matthew C Weston

    2014-02-01

    Full Text Available The Pten and Tsc1 genes both encode proteins that repress mechanistic target of rapamycin (mTOR signaling. Disruption of either gene in the brain results in epilepsy and autism-like symptoms in humans and mouse models, therefore it is important to understand the molecular and physiological events that lead from gene disruption to disease phenotypes. Given the similar roles these two molecules play in the regulation of cellular growth and the overlap in the phenotypes that result from their loss, we predicted that the deletion of either the Pten or Tsc1 gene from hippocampal neurons would have similar effects on neuronal morphology and synaptic transmission. Accordingly, we found that loss of either Pten or Tsc1 caused comparable increases in soma size, dendrite length and action potential properties. However, the effects of Pten and Tsc1 loss on synaptic transmission were different. Loss of Pten lead to an increase in both excitatory and inhibitory neurotransmission, while loss of Tsc1 did not affect excitatory neurotransmission and reduced inhibitory transmission by decreasing mIPSC amplitude. Although the loss of Pten or Tsc1 both increased downstream mTORC1 signaling, phosphorylation of Akt was increased in Pten-ko and decreased in Tsc1-ko neurons, potentially accounting for the different effects on synaptic transmission. Despite the different effects at the synaptic level, our data suggest that loss of Pten or Tsc1 may both lead to an increase in the ratio of excitation to inhibition at the network level, an effect that has been proposed to underlie both epilepsy and autism.

  19. Stimulus Configuration, Classical Conditioning, and Hippocampal Function.

    Science.gov (United States)

    Schmajuk, Nestor A.; DiCarlo, James J.

    1991-01-01

    The participation of the hippocampus in classical conditioning is described in terms of a multilayer network portraying stimulus configuration. A model of hippocampal function is presented, and computer simulations are used to study neural activity in the various brain areas mapped according to the model. (SLD)

  20. 基质细胞衍生因子对海马神经细胞迁移的影响%Stromal derived factor 1 alpha alters migration of hippocampal cells cultured in vitro

    Institute of Scientific and Technical Information of China (English)

    王丽君; 刘素芳; 韩雪飞; 严静; 郭美霞; 邢莹

    2011-01-01

    目的 观察不同浓度的SDF1 alpha对体外培养的海马神经细胞迁移的影响.方法 通过Transwell小室方法观察细胞在轴突导向因子诱导下穿过多孔滤膜的情况.将分离的海马神经细胞种入上室内,并且上室内细胞培养基均为无血清培养基(饥饿疗法),下室内则分别采用含有0、50、100、150、200、250、300ng/ml的SDF1 alpha的培养基(对照组含有0ng/ml的SDF1 alpha)12h后,观察迁移的神经细胞数量,统计后找到最佳实验剂量.采用最佳实验剂量作用细胞24h,观察神经细胞形态学的变化.结果 不同浓度的SDF1 alpha作用12h后,迁移的神经细胞数量分别为16.67±1.21、16.83±2.14、35.50±4.32、36.33±1.21、36.83±1.94和38.17±2.71,与对照组迁移的神经细胞数量9.17±2.14相比,有显著性差异.采用150ng/ml的SDF1 alpha作用细胞24h,神经细胞突起延长.结论 SDF1 alpha可以促进体外培养的海马神经细胞迁移和突起延长.%Objective Stromal cell-derived factor-1 ( SDF1 ) alpha, a kind of chemotactic protein,is secreted by marrow stromal cells to exert its function in immune system.Recently, studies have shown that SDF1alpha expresses in the brain,which suggests that SDF1alpha may play an important role in nervous system.This study is to culture hippocampal cells in vitro to detect the function of SDF1 alpha on cell migration and neurite outgrowth.Methods Primary hippocampus neurons were obtained from newborn SD rats.Bilateral hippocampi were carefully dissected and digested in 0.25% trypsin at 37℃ for 5 minutes.The in vitro migration study was carried out with transwell assay.Cells were plated into the upper layer of the transwell device.Medium with varying doses of SDF1alpha were placed into the lower layer.After 12-hour incubation at 37℃ in 5% CO2 ,the incubation medium was discarded and the membrane was washed with PBS twice.The cells on the upper layer of the filtering film were wiped away with cotton

  1. Microglial VPAC1R mediates a novel mechanism of neuroimmune-modulation of hippocampal precursor cells via IL-4 release.

    Science.gov (United States)

    Nunan, Robert; Sivasathiaseelan, Harri; Khan, Damla; Zaben, Malik; Gray, William

    2014-08-01

    Neurogenesis, the production of new neurons from neural stem/progenitor cells (NSPCs), occurs throughout adulthood in the dentate gyrus of the hippocampus, where it supports learning and memory. The innate and adaptive immune systems are increasingly recognized as important modulators of hippocampal neurogenesis under both physiological and pathological conditions. However, the mechanisms by which the immune system regulates hippocampal neurogenesis are incompletely understood. In particular, the role of microglia, the brains resident immune cell is complex, as they have been reported to both positively and negatively regulate neurogenesis. Interestingly, neuronal activity can also regulate the function of the immune system. Here, we show that depleting microglia from hippocampal cultures reduces NSPC survival and proliferation. Furthermore, addition of purified hippocampal microglia, or their conditioned media, is trophic and proliferative to NSPCs. VIP, a neuropeptide released by dentate gyrus interneurons, enhances the proliferative and pro-neurogenic effect of microglia via the VPAC1 receptor. This VIP-induced enhancement is mediated by IL-4 release, which directly targets NSPCs. This demonstrates a potential neuro-immuno-neurogenic pathway, disruption of which may have significant implications in conditions where combined cognitive impairments, interneuron loss, and immune system activation occurs, such as temporal lobe epilepsy and Alzheimer's disease.

  2. Expression and activation of proteases in co-cultures.

    Science.gov (United States)

    Paduch, Roman; Kandefer-Szerszeń, Martyna

    2011-01-01

    The present study concerned the expression and activation of metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9) and the urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) system in co-cultures of human colon carcinoma cell spheroids (HT29, LS180, SW948) with human normal colon epithelium (CCD 841 CoTr), myofibroblasts (CCD-18Co) and endothelial cells (HUVEC). Additionally, the influence of monensin on the production and function of the proteases was tested. Tumor cells expressed small amounts of MMP-2, MMP-9 and uPA. Normal cells generally produced proportionally higher concentrations of these proteases (especially MMP-2, compared with significantly smaller yields of MMP-9 and significantly lower amounts of uPAR than tumors. In co-cultures of tumor spheroids with normal cell monolayers, the concentration of the proteases was equal to the sum of the enzymes produced in monocultures of both types of cells. The highest activity of uPA, measured as the reduction of the chromogenic substrate (S-2444), was detected in supernatants and lysates of endothelial cells. Interestingly, in normal cells, the higher expression of proteases, mainly uPA, measured as the level of protein concentration, was closely linked with their lower activity and inversely, in tumor cells, the low level of the expression of the enzymes correlated with their high enzymatic activity. In zymography analysis, mainly pro-MMPs were detected both in culture supernatants and cell lysates. The highest amounts of active forms of the MMPs were detected in tumor spheroids co-cultured with endothelial cells. Monensin inhibited MMPs and uPA secretion but significantly increased uPAR release, mainly from normal cells. In conclusion, during direct interactions of tumor cells with normal cells, MMPs and the uPA/uPAR system play an important role in the degradation of ECM and tumor development, but as we found, there is a reverse relationship between the concentration and the

  3. Plant Cell Cultures as Source of Cosmetic Active Ingredients

    Directory of Open Access Journals (Sweden)

    Ani Barbulova

    2014-04-01

    Full Text Available The last decades witnessed a great demand of natural remedies. As a result, medicinal plants have been increasingly cultivated on a commercial scale, but the yield, the productive quality and the safety have not always been satisfactory. Plant cell cultures provide useful alternatives for the production of active ingredients for biomedical and cosmetic uses, since they represent standardized, contaminant-free and biosustainable systems, which allow the production of desired compounds on an industrial scale. Moreover, thanks to their totipotency, plant cells grown as liquid suspension cultures can be used as “biofactories” for the production of commercially interesting secondary metabolites, which are in many cases synthesized in low amounts in plant tissues and differentially distributed in the plant organs, such as roots, leaves, flowers or fruits. Although it is very widespread in the pharmaceutical industry, plant cell culture technology is not yet very common in the cosmetic field. The aim of the present review is to focus on the successful research accomplishments in the development of plant cell cultures for the production of active ingredients for cosmetic applications.

  4. Enhanced Hippocampal Neurogenesis in the Absence of Microglia T Cell Interaction and Microglia Activation in the Murine Running Wheel Model

    NARCIS (Netherlands)

    Olah, Marta; Ping, Gao; De Haas, Alexander H.; Brouwer, Niesike; Meerlo, Peter; Van Der Zee, Eddy A.; Biber, Knut; Boddeike, Hendrikus W. G. M.; Brouwer, Nieske; Boddeke, Hendrikus W.G.M.

    2009-01-01

    Recently, activated microglia have been shown to be involved in the regulation of several aspects of neurogenesis under certain experimental conditions both in vitro and in vivo. A neurogenesis supportive microglia phenotype has been suggested to arise from the interaction of microglia with homing e

  5. Correlates of college students' physical activity: cross-cultural differences.

    Science.gov (United States)

    Seo, Dong-Chul; Torabi, Mohammad R; Jiang, Nan; Fernandez-Rojas, Xinia; Park, Bock-Hee

    2009-10-01

    This study examined cross-cultural differences in personal and behavioral determinants of vigorous-intensity and moderate-intensity physical activity (PA) among college students living in distinctly different cultures, that is, the United States, Costa Rica, India, and South Korea. Participants of this study were recruited from randomly chosen public universities in the 4 countries during the 2006-2007 academic year. A total of 4685 students participated in the study (response rate 90%). Vigorous-intensity PA was measured by asking on how many of the past 7 days the participants participated in PA for at least 20 minutes that made them sweat or breathe hard. For moderate-intensity PA, participants were asked on how many of the past 7 days they participated in PA for at least 30 minutes that did not make them sweat or breathe hard. Findings indicate that whereas perceived overweight and fruit and vegetable consumption are relatively culture-free predictors of PA, gender and TV/video watching are culture-specific predictors. Binge drinking was not predictive of meeting the vigorous-intensity and moderate-intensity PA guidelines in any of the 4 countries. PMID:19661101

  6. A role for interleukin-1β in determining the lineage fate of embryonic rat hippocampal neural precursor cells.

    Science.gov (United States)

    Green, Holly F; Treacy, Eimear; Keohane, Aoife K; Sullivan, Aideen M; O'Keeffe, Gerard W; Nolan, Yvonne M

    2012-03-01

    Neurogenesis occurs in the hippocampus of the developing and adult brain due to the presence of multipotent stem cells and restricted precursor cells at different stages of differentiation. It has been proposed that they may be of potential benefit for use in cell transplantation approaches for neurodegenerative disorders and trauma. Prolonged release of interleukin-1β (IL-1β) from activated microglia has a deleterious effect on hippocampal neurons and is implicated in the impaired neurogenesis and cognitive dysfunction associated with aging, Alzheimer's disease and depression. This study assessed the effect of IL-1β on the proliferation and differentiation of embryonic rat hippocampal NPCs in vitro. We show that IL-1R1 is expressed on proliferating NPCs and that IL-1β treatment decreases cell proliferation and neurosphere growth. When NPCs were differentiated in the presence of IL-1β, a significant reduction in the percentages of newly-born neurons and post-mitotic neurons and a significant increase in the percentage of astrocytes was observed in these cultures. These effects were attenuated by IL-1 receptor antagonist. These data reveal that IL-1β exerts an anti-proliferative, anti-neurogenic and pro-gliogenic effect on embryonic hippocampal NPCs, which is mediated by IL-1R1. The present results emphasise the consequences of an inflammatory environment during NPC development, and indicate that strategies to inhibit IL-1β signalling may be necessary to facilitate effective cell transplantation approaches or in conditions where endogenous hippocampal neurogenesis is impaired.

  7. BDNF pro-peptide actions facilitate hippocampal LTD and are altered by the common BDNF polymorphism Val66Met.

    Science.gov (United States)

    Mizui, Toshiyuki; Ishikawa, Yasuyuki; Kumanogoh, Haruko; Lume, Maria; Matsumoto, Tomoya; Hara, Tomoko; Yamawaki, Shigeto; Takahashi, Masami; Shiosaka, Sadao; Itami, Chiaki; Uegaki, Koichi; Saarma, Mart; Kojima, Masami

    2015-06-01

    Most growth factors are initially synthesized as precursor proteins and subsequently processed into their mature form by proteolytic cleavage, resulting in simultaneous removal of a pro-peptide. However, compared with that of mature form, the biological role of the pro-peptide is poorly understood. Here, we investigated the biological role of the pro-peptide of brain-derived neurotrophic factor (BDNF) and first showed that the pro-peptide is expressed and secreted in hippocampal tissues and cultures, respectively. Interestingly, we found that the BDNF pro-peptide directly facilitates hippocampal long-term depression (LTD), requiring the activation of GluN2B-containing NMDA receptors and the pan-neurotrophin receptor p75(NTR). The BDNF pro-peptide also enhances NMDA-induced α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor endocytosis, a mechanism crucial for LTD expression. Thus, the BDNF pro-peptide is involved in synaptic plasticity that regulates a mechanism responsible for promoting LTD. The well-known BDNF polymorphism valine for methionine at amino acid position 66 (Val66Met) affects human memory function. Here, the BDNF pro-peptide with Met mutation completely inhibits hippocampal LTD. These findings demonstrate functional roles for the BDNF pro-peptide and a naturally occurring human BDNF polymorphism in hippocampal synaptic depression. PMID:26015580

  8. Resveratrol Prevents Age-Related Memory and Mood Dysfunction with Increased Hippocampal Neurogenesis and Microvasculature, and Reduced Glial Activation

    OpenAIRE

    Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K.

    2015-01-01

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for e...

  9. Environmental Novelty Activates β2-Adrenergic Signaling to Prevent the Impairment of Hippocampal LTP by Aβ Oligomers

    OpenAIRE

    Li, Shaomin; Jin, Ming; Zhang, Dainan; Yang, Ting; Koeglsperger, Thomas; Fu, Hongjun; Selkoe, Dennis J.

    2013-01-01

    A central question about human brain aging is whether cognitive enrichment slows the development of Alzheimer changes. Here we show that prolonged exposure to an enriched environment (EE) facilitated signaling in the hippocampus of wild-type mice that promoted long-term potentiation. A key feature of the EE effect was activation of β2-adrenergic receptors and downstream cAMP/PKA signaling. This EE pathway prevented LTP inhibition by soluble oligomers of amyloid β-protein (Aβ) isolated from AD...

  10. Nocturnal Mnemonics: Sleep and Hippocampal Memory Processing

    Directory of Open Access Journals (Sweden)

    Jared M. Saletin

    2012-05-01

    Full Text Available As critical as waking brain function is to learning and memory, an established literature now describes an equally important yet complementary role for sleep in information processing. This overview examines the specific contribution of sleep to human hippocampal memory processing; both the detriments caused by a lack of sleep, and conversely, the proactive benefits that develop following the presence of sleep. First, a role for sleep before learning is discussed, preparing the hippocampus for initial memory encoding. Second, a role for sleep after learning is considered, modulating the post-encoding consolidation of hippocampal-dependent memory. Third, a model is outlined in which these encoding and consolidation operations are symbiotically accomplished, associated with specific NREM sleep physiological oscillations. As a result, the optimal network outcome is achieved, increasing hippocampal independence and hence overnight consolidation, while restoring next-day sparse hippocampal encoding capacity for renewed learning ability upon awakening. Finally, emerging evidence is considered suggesting that, unlike previous conceptions, sleep does not universally consolidate all information equally. Instead, and based on explicit as well as motivational cues during initial encoding, sleep executes the discriminatory offline consolidation only of select information. Consequently, sleep promotes the targeted strengthening of some memories while actively forgetting others; a proposal with significant theoretical and clinical ramifications.

  11. Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen-glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

    DEFF Research Database (Denmark)

    Montero, Maria; Rom Poulsen, Frantz; Noraberg, Jens;

    2007-01-01

    In addition to its well-known hematopoietic effects, erythropoietin (EPO) also has neuroprotective properties. However, hematopoietic side effects are unwanted for neuroprotection, underlining the need for EPO-like compounds with selective neuroprotective actions. One such compound, devoid...... cultures. To elucidate a possible mechanism involved in EPO and CEPO neuroprotection against OGD, the integrity of alpha-II-spectrin cytoskeletal protein was studied. Both EPO and CEPO significantly reduced formation of spectrin cleavage products in the OGD model. We conclude that CEPO is at least...

  12. Prenatal activation of toll-like receptor-4 dampens adult hippocampal neurogenesis in an IL-6 dependent manner

    Directory of Open Access Journals (Sweden)

    Abdeslam eMouihate

    2016-06-01

    Full Text Available Prenatal immune challenge has been associated with alteration in brain development and plasticity that last into adulthood. We have previously shown that prenatal activation of toll-like receptor 4 by LPS induces IL-6-dependent STAT-3 signaling pathway in the fetal brain. Whether this IL-6-dependent activation of fetal brain results in long lasting impact in brain plasticity is still unknown. Furthermore, it has been shown that prenatal LPS heightens the hypothalamic-pituitary-adrenal (HPA response in adulthood. In the present study we tested whether LPS administration during pregnancy affects neurogenesis in adult male offspring. Because corticosterone, the end-product of HPA axis activity in rats, alters neurogenesis we tested whether this enhanced HPA axis responsiveness in adult male offspring played a role in the long lasting impact of LPS on neurogenesis during adulthood. Pregnant rats were given either LPS, or LPS and an IL-6 neutralizing antibody (IL-6Ab. The newly born neurons were monitored in the subventricular zone (SVZ and the dentate gyrus (DG of the hippocampus of adult male offspring by monitoring doublecortin and T-box brain protein 2 expression: two well-established markers of newly born neurons. Prenatal LPS decreased the number of newly born neurons in the DG, but not in the SVZ of adult offspring. This decreased number of newly born neurons in the DG was absent when IL-6Ab was co-injected with LPS during pregnancy. Furthermore, administration of a corticosterone receptor blocker, RU-486, to adult offspring blunted the prenatal LPS induced decrease in newly born neurons in the DG.These data suggest that maternally triggered IL-6 plays a crucial role in the long lasting impact of LPS on adult neurogenesis.

  13. Different mechanisms must be considered to explain the increase in hippocampal neural precursor cell proliferation by physical activity

    Directory of Open Access Journals (Sweden)

    Rupert W Overall

    2016-08-01

    Full Text Available The number of proliferating neural precursor cells in the adult hippocampus is strongly increased by physical activity. The mechanisms through which this behavioral stimulus induces cell proliferation, however, are not yet understood. In fact, even the mode of proliferation of the stem and progenitor cells is not exactly known. Evidence exists for several mechanisms including cell cycle shortening, reduced cell death and stem cell recruitment, but as yet no model can account for all observations. An appreciation of how the cells proliferate, however, is crucial to our ability to model the neurogenic process and predict its behavior in response to pro-neurogenic stimuli. In a recent study, we addressed modulation of the cell cycle length as one possible mode of regulation of precursor cell proliferation in running mice. Our results indicated that the observed increase in number of proliferating cells could not be explained through a shortening of the cell cycle. We must therefore consider other mechanisms by which physical activity leads to enhanced precursor cell proliferation. Here we review the evidence for and against several different hypotheses and discuss the implications for future research in the field.

  14. Different Mechanisms Must Be Considered to Explain the Increase in Hippocampal Neural Precursor Cell Proliferation by Physical Activity

    Science.gov (United States)

    Overall, Rupert W.; Walker, Tara L.; Fischer, Tim J.; Brandt, Moritz D.; Kempermann, Gerd

    2016-01-01

    The number of proliferating neural precursor cells in the adult hippocampus is strongly increased by physical activity. The mechanisms through which this behavioral stimulus induces cell proliferation, however, are not yet understood. In fact, even the mode of proliferation of the stem and progenitor cells is not exactly known. Evidence exists for several mechanisms including cell cycle shortening, reduced cell death and stem cell recruitment, but as yet no model can account for all observations. An appreciation of how the cells proliferate, however, is crucial to our ability to model the neurogenic process and predict its behavior in response to pro-neurogenic stimuli. In a recent study, we addressed modulation of the cell cycle length as one possible mode of regulation of precursor cell proliferation in running mice. Our results indicated that the observed increase in number of proliferating cells could not be explained through a shortening of the cell cycle. We must therefore consider other mechanisms by which physical activity leads to enhanced precursor cell proliferation. Here we review the evidence for and against several different hypotheses and discuss the implications for future research in the field. PMID:27536215

  15. Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation.

    Science.gov (United States)

    Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K

    2015-01-28

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.

  16. Rhythms of the hippocampal network.

    Science.gov (United States)

    Colgin, Laura Lee

    2016-04-01

    The hippocampal local field potential (LFP) shows three major types of rhythms: theta, sharp wave-ripples and gamma. These rhythms are defined by their frequencies, they have behavioural correlates in several species including rats and humans, and they have been proposed to carry out distinct functions in hippocampal memory processing. However, recent findings have challenged traditional views on these behavioural functions. In this Review, I discuss our current understanding of the origins and the mnemonic functions of hippocampal theta, sharp wave-ripples and gamma rhythms on the basis of findings from rodent studies. In addition, I present an updated synthesis of their roles and interactions within the hippocampal network. PMID:26961163

  17. TERATOGENICITY OF CYCLOPHOSPHAMIDE IN A COUPLED MICROSOMAL ACTIVATING/EMBRYO CULTURE SYSTEM

    Science.gov (United States)

    Using the coupled microsomal activating/embryo culture system, in vitro experiments were performed to establish the role of metabolism in the embryo toxicity and teratogenicity of cyclophosphamide. Cyclophosphamide in the coupled microsomal activating/embryo culture system produc...

  18. Preplay of future place cell sequences by hippocampal cellular assemblies

    OpenAIRE

    Dragoi, George; Tonegawa, Susumu

    2010-01-01

    During spatial exploration, hippocampal neurons show a sequential firing pattern in which individual neurons fire specifically at particular locations along the animal’s trajectory (place cells1, 2). According to the dominant model of hippocampal cell assembly activity, place cell firing order is established for the first time during exploration, to encode the spatial experience, and is subsequently replayed during rest3, 4, 5, 6 or slow-wave sleep7, 8, 9, 10 for consolidation of the encoded ...

  19. Further activities of safety culture toward nuclear transportation industry

    International Nuclear Information System (INIS)

    On September 30, 1999, a criticality accident occurred at the uranium processing facility of the JCO Co. Ltd. (hereinafter referred to as ''JCO'') Tokai plant, located in Tokaimura, Ibaraki Prefecture. This was an unprecedented accident in Japan's history of peaceful use of nuclear power, resulting in three workers exposed to severe radiation, two of whom died, and the evacuation and enforced indoor confinement of local residents. Nuclear power suppliers must take personal responsibility for ensuring safety. In this connection, the electric power industry, heavy electric machinery manufacturers, fuel fabricators, and nuclear power research organizations gathered together to establish the Nuclear Safety Network (NSnet) in December 1999, based on the resolve to share and improve the level of the safety culture across the entire nuclear power industry and to assure that such an accident never occurs again. NSnet serves as a link between nuclear power enterprises, research organizations, and other bodies, based on the principles of equality and reciprocity. A variety of activities are pursued, such as diffusing a safety culture, implementing mutual evaluation among members, and exchanging safety-related information. Aiming to share and improve the safety culture throughout the entire nuclear power industry, NSnet thoroughly implements the principle of safety first, while at the same time making efforts to restore trust in nuclear power

  20. The use of organotypic hippocampal slice cultures to evaluate protection by non-competitive NMDA receptor antagonists against excitotoxicity

    DEFF Research Database (Denmark)

    Ring, Avi; Tanso, Rita; Noraberg, Jens

    2010-01-01

    There is a wide interest in testing neuroprotectants which inhibit the neurodegeneration that results from excessive activation of brain NMDA receptors.  As an alternative to in vivo testing in animal models we demonstrate here the use of a complex in vitro model to compare the efficacy and toxic...

  1. Hippocampal lesions impair rapid learning of a continuous spatial alternation task.

    Directory of Open Access Journals (Sweden)

    Steve M Kim

    Full Text Available The hippocampus is essential for the formation of memories for events, but the specific features of hippocampal neural activity that support memory formation are not yet understood. The ideal experiment to explore this issue would be to monitor changes in hippocampal neural coding throughout the entire learning process, as subjects acquire and use new episodic memories to guide behavior. Unfortunately, it is not clear whether established hippocampally-dependent learning paradigms are suitable for this kind of experiment. The goal of this study was to determine whether learning of the W-track continuous alternation task depends on the hippocampal formation. We tested six rats with NMDA lesions of the hippocampal formation and four sham-operated controls. Compared to controls, rats with hippocampal lesions made a significantly higher proportion of errors and took significantly longer to reach learning criterion. The effect of hippocampal lesion was not due to a deficit in locomotion or motivation, because rats with hippocampal lesions ran well on a linear track for food reward. Rats with hippocampal lesions also exhibited a pattern of perseverative errors during early task experience suggestive of an inability to suppress behaviors learned during pretraining on a linear track. Our findings establish the W-track continuous alternation task as a hippocampally-dependent learning paradigm which may be useful for identifying changes in the neural representation of spatial sequences and reward contingencies as rats learn and apply new task rules.

  2. Sleep-stage correlates of hippocampal electroencephalogram in primates.

    Directory of Open Access Journals (Sweden)

    Ryoi Tamura

    Full Text Available It has been demonstrated in the rodent hippocampus that rhythmic slow activity (theta predominantly occurs during rapid eye movement (REM sleep, while sharp waves and associated ripples occur mainly during non-REM sleep. However, evidence is lacking for correlates of sleep stages with electroencephalogram (EEG in the hippocampus of monkeys. In the present study, we recorded hippocampal EEG from the dentate gyrus in monkeys overnight under conditions of polysomnographical monitoring. As result, the hippocampal EEG changed in a manner similar to that of the surface EEG: during wakefulness, the hippocampal EEG showed fast, desynchronized waves, which were partly replaced with slower waves of intermediate amplitudes during the shallow stages of non-REM sleep. During the deep stages of non-REM sleep, continuous, slower oscillations (0.5-8 Hz with high amplitudes were predominant. During REM sleep, the hippocampal EEG again showed fast, desynchronized waves similar to those found during wakefulness. These results indicate that in the monkey, hippocampal rhythmic slow activity rarely occurs during REM sleep, which is in clear contrast to that of rodents. In addition, the increase in the slower oscillations of hippocampal EEG during non-REM sleep, which resembled that of the surface EEG, may at least partly reflect cortical inputs to the dentate gyrus during this behavioral state.

  3. Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bernardino, Liliana; Xapelli, Sara; Silva, Ana P;

    2005-01-01

    The inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects...... by macrophage antigen-1 and bromodeoxyuridine immunohistochemistry, suggesting a functional recruitment of cytokine-producing cells at sites of neurodegeneration. Together, these findings are relevant for understanding the role of proinflammatory cytokines and microglia activation in acute and chronic...

  4. Micropropagation of orchid hybrids in knudson culture medium with addiction of vitamins of ms culture medium, benzilaminopurine and activated charcoal

    Directory of Open Access Journals (Sweden)

    Fabíola Villa

    2014-02-01

    Full Text Available The genera Cattleya and Brassavola, naturally occurring in Brazil, are widely used in hybridization to obtain better shape of the lip in the hybrids. This demand creates the need to develop more effective propagation to meet the market and contributing to avoid the extinction of these plants. This study aimed to test BAP concentrations, activated charcoal, culture medium Knudson and culture medium MS’s vitamins in subculture of Brassocattleya Pastoral x Laeliocattleya Amber Glow orchids plants. There were used seedlings from in vitro germination, with 1-1.5 cm length, undergoing standardization in the culture medium Knudson for three months. The experiment were performed using concentrations of culture medium Knudson (0%, 50%, 100%, 150% and 200%, combined with concentrations of culture medium MS’s vitamins (0%, 50%, 100% and 200% and BAP concentrations (0; 1.0; 2.0 and 4.0 mg L-1 versus activated charcoal (0, 200, 400 and 600 mg L-1, incorporated in a culture medium Knudson. In each flask of 250 mL containing approximately 50 mL of culture medium, four seedlings were placed under aseptic conditions. It was concluded that can use 129% of Knudson, supplemented with 137.5 mg L-1 activated charcoal, 104% of vitamin MS medium without addition of BAP as the best composition for culture medium of hybrid orchid in vitro propagation. The Knudson culture medium does not promote increase in the root system.

  5. Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

    International Nuclear Information System (INIS)

    Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic

  6. Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Pizzurro, Daniella M.; Dao, Khoi [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Costa, Lucio G. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Department of Neuroscience, University of Parma, Parma (Italy)

    2014-02-01

    Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic

  7. Relation between hippocampal gamma waves and behavioral disturbances induced by phencyclidine and methamphetamine.

    Science.gov (United States)

    Ma, J; Leung, L S

    2000-06-15

    The relationship between hippocampal electrical activity and behavioral hyperactivity induced by either phencyclidine (PCP) or methamphetamine (MAP) was examined in freely behaving rats. The EEGs at the hippocampal CA1 region were simultaneously recorded with the animal's behavior for 2 h after administration of either PCP or MAP. PCP (10 mg/kg, intraperitoneal (i.p.)) significantly increased locomotor activity including rearing, walking, head-weaving and circling. Spectral analysis of the EEG showed that hippocampal gamma waves (30-70 Hz), but not other frequency bands, were significantly increased from 5 to 120 min after systemic injection of PCP. Inactivation of the medial septum with muscimol, a gamma-aminobutyric acid receptor A agonist, 15 min prior to injection of PCP, suppressed both hippocampal gamma waves and locomotor activity. MAP (1.5 mg/kg, i.p.) also increased locomotor activity for longer than 2 h. During the behavioral hyperactivity induced by MAP, hippocampal EEG showed θ and gamma rhythms that were not significantly different from those during walking before MAP. However, MAP-induced behavioral activity was suppressed by pre-injection of muscimol in the medial septum, which also decreased hippocampal gamma activity. It is suggested that the medial septum plays a role in mediating behavioral disturbances induced by both PCP and MAP through control of the hippocampal electrical activity, and that hippocampal gamma waves may play a permissible role in the expression of behaviors.

  8. Religious factors and hippocampal atrophy in late life.

    Directory of Open Access Journals (Sweden)

    Amy D Owen

    Full Text Available Despite a growing interest in the ways spiritual beliefs and practices are reflected in brain activity, there have been relatively few studies using neuroimaging data to assess potential relationships between religious factors and structural neuroanatomy. This study examined prospective relationships between religious factors and hippocampal volume change using high-resolution MRI data of a sample of 268 older adults. Religious factors assessed included life-changing religious experiences, spiritual practices, and religious group membership. Hippocampal volumes were analyzed using the GRID program, which is based on a manual point-counting method and allows for semi-automated determination of region of interest volumes. Significantly greater hippocampal atrophy was observed for participants reporting a life-changing religious experience. Significantly greater hippocampal atrophy was also observed from baseline to final assessment among born-again Protestants, Catholics, and those with no religious affiliation, compared with Protestants not identifying as born-again. These associations were not explained by psychosocial or demographic factors, or baseline cerebral volume. Hippocampal volume has been linked to clinical outcomes, such as depression, dementia, and Alzheimer's Disease. The findings of this study indicate that hippocampal atrophy in late life may be uniquely influenced by certain types of religious factors.

  9. Inhibitory microcircuit modules in hippocampal learning.

    Science.gov (United States)

    Caroni, Pico

    2015-12-01

    It has recently become possible to investigate connectivities and roles of identified hippocampal GABAergic interneurons (INs) in behaving rodents. INs targeting distinct pyramidal neuron subcompartments are recruited dynamically at defined phases of behavior and learning. They include Parvalbumin Axo-axonic and perisomatic Basket cells, and Somatostatin radiatum-oriens and oriens-lacunosum moleculare cells. Each IN is in turn either activated or inhibited upon specific behavioral and network state requirements through specific inputs and neuromodulators. Subpopulations of these principal neurons and INs interconnect selectively, suggesting selective processing and routing of alternate information streams. First canonical functional modules have emerged, which will have to be further defined and linked to identified afferents and efferents towards a circuit understanding of how hippocampal networks support behavior.

  10. Organisational Culture as a Dominant in Enterprise Activity: System Approach

    Directory of Open Access Journals (Sweden)

    Serikov Anatoliy V.

    2014-01-01

    Full Text Available The article offers a “conceptual carcass” of the enterprise model, which is based on known results of studies in sociology, biology, system theory and mathematics. The article lists main features of growth of main indicators of economic activity and development of an enterprise. Dynamics of changes at an enterprise is described with a system of non-linear differential equations. One of the global and dominating factors in it is entrepreneurship of personnel, which is an integral part of its labour mentality or organisational culture. The article proves for the first time ever, using mathematical modelling, that namely entrepreneurship, innovation capability, is a comprehensive and dominant factor of enterprise growth and development.

  11. Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Harrell, L.E.; Davis, J.N.

    1984-07-01

    Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-(/sup 3/H)glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity.

  12. Neuroprotection of n-Butanol Extract from Roots of Potentilla anserina on Hypoxic Injury in Primary Hippocampal Neurons

    Institute of Scientific and Technical Information of China (English)

    QIN Xiao-jing; LI Ling-zhi; LV Qi; YU Bao-guo; YANG Shu-wang; HE Tao; ZHANG Yong-liang

    2012-01-01

    Objective To investigate the protective effect of n-butanol extract from the roots of Potentilla anserina (NP) on hypoxic hippocampal neurons in neonatal rats.Methods Primary cultured hippocampal neurons were pretreated with different concentration of NP (0.25,0.0625,and 0.0156 mg/mL) before incubation in a low oxygen (0.1%) environment for 4 h.Cell viability was evaluated by Trypan blue staining assay.Lactate dehydrogenase (LDH) released by neurons into the medium was measured.The activity of superoxide dismutase (SOD) in cell cytosol was determined using nitroblue tetrazolium.Morphological changes and mitochondrial function were observed by transmission electron microscopy.Results Hypoxic injury could decrease the cells viability of neuron,enhance LDH release (P < 0.05),decrease SOD activity,and increase mitochondrial injury.Pretreatment with NP significantly increased cell viability,decreased LDH release (P < 0.05),promoted SOD activity (P < 0.05),and remarkably improved cellular ultra-microstructure compared with the model group.Conclusion NP could protect the primary hippocampal neurons from hypoxic injury by attenuating mitochondrial cell death.

  13. Involvement of microglia activation in the lead induced long-term potentiation impairment.

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    Ming-Chao Liu

    Full Text Available Exposure of Lead (Pb, a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α, interleukin-1β (IL-1β and inducible nitric oxide synthase (iNOS in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits.

  14. Aberrant hippocampal neurogenesis after limbic kindling: Relationship to BDNF and hippocampal-dependent memory.

    Science.gov (United States)

    Botterill, J J; Brymer, K J; Caruncho, H J; Kalynchuk, L E

    2015-06-01

    Seizures dramatically increase the number of adult generated neurons in the hippocampus. However, it is not known whether this effect depends on seizures that originate in specific brain regions or whether it is nonspecific to seizure activity regardless of origin. We used kindling of different brain sites to address this question. Rats received 99 kindling stimulations of the basolateral amygdala, dorsal hippocampus, or caudate nucleus over a 6-week period. After kindling, we counted the number of adult generated hippocampal neurons that were birth-dated with the proliferative marker bromodeoxyuridine (BrdU) to evaluate cell proliferation and survival under conditions of repeated seizures. Next, we counted the number of doublecortin immunoreactive (DCX-ir) cells and evaluated their dendritic complexity to determine if limbic and nonlimbic seizures have differential effects on neuronal maturation. We also quantified hippocampal brain-derived neurotrophin factor (BDNF) protein levels using an ELISA kit and assessed memory performance using a hippocampal-dependent fear conditioning paradigm. We found that limbic, but not nonlimbic, seizures dramatically increased hippocampal cell proliferation and the number of hilar-CA3 ectopic granule cells. Further, limbic kindling promoted dendritic outgrowth of DCX-ir cells and the number of DCX-ir cells containing basal dendrites. Limbic kindling also enhanced BDNF protein levels throughout the entire hippocampus and impaired the retrieval of fear memories. Collectively, our results suggest a relationship between limbic seizures, neurogenesis, BDNF protein, and cognition.

  15. Exploring Formative Assessment Using Cultural Historical Activity Theory

    Directory of Open Access Journals (Sweden)

    Mandy Asghar

    2013-02-01

    Full Text Available Formative assessment is a pedagogic practice that has been the subject of much research and debate, as to how it can be used most effectively to deliver enhanced student learning in the higher education setting. Often described as a complex concept it embraces activities that range from facilitating students understanding of assessment standards, to providing formative feedback on their work; from very informal opportunities of engaging in conversations, to the very formal process of submitting drafts of work. This study aims to show how cultural historical activity theory can be used as a qualitative analysis framework to explore the complexities of formative assessment as it is used in higher education. The original data for the research was collected in 2008 by semi structured interviews and analysed using a hermeneutic phenomenological approach. For this present paper three selected transcripts were re-examined, using a case study approach that sought to understand and compare the perceptions of five academic staff, from three distinct subject areas taught within a UK university. It is proposed that using activity theory can provide insight into the complexity of such experiences, about what teachers do and why, and the influence of the community in which they are situated. Individually the cases from each subject area were analysed using activity theory exploring how the mediating artefacts of formative assessment were used; the often implicit rules that governed their use and the roles of teachers and students within the local subject community. The analysis also considered the influence each aspect of the unit of activity had on the other in understanding formative assessment practice. Subsequently the three subject cases were compared and contrasted. The findings illuminate a variety of practices, including how students and staff engage together in formative assessment activities and for some, how dialogue is used as one of the key tools

  16. Measuring Chitinase and Protease Activity in Cultures of Fungal Entomopathogens.

    Science.gov (United States)

    Cheong, Peter; Glare, Travis R; Rostás, Michael; Haines, Stephen R

    2016-01-01

    Entomopathogenic fungi produce a variety of destructive enzymes and metabolites to overcome the unique defense mechanisms of insects. In a first step, fungal chitinases and proteinases need to break down the insect's cuticle. Both enzyme classes support the infection process by weakening the chitin barrier and by producing nutritional cleavage products for the fungus. In a second step, the pathogen can now mechanically penetrate the weakened cuticle and reach the insect's hemolymph where it starts proliferating. The critical enzymes chitinase and proteinase are also excreted into the supernatants of fungal cultures and can be used as indicators of virulence. Chromogenic assays adapted for 96-well microtiter plates that measure these enzymes provide a sensitive, fast, and easy screening method for evaluating the potential biocontrol activity of fungal isolates and may be considered as an alternative to laborious and time-consuming bioassays. Furthermore, monitoring fungal enzyme production in dependence of time, nutrient sources, or other factors can facilitate in establishing optimal growth and harvesting conditions for selected isolates with the aim of achieving maximum biocontrol activity. PMID:27565500

  17. Activity of protease-activated receptors in primary cultured human myenteric neurons

    Directory of Open Access Journals (Sweden)

    Eva Maria Kugler

    2012-09-01

    Full Text Available Activity of the four known protease-activated receptors (PARs has been well studied in rodent enteric nervous system and results in animal models established an important role for neuronal PAR2. We recently demonstrated that, unlike in rodents, PAR1 is the dominant neuronal protease receptor in the human submucous plexus. With this study we investigated whether this also applies to the human myenteric plexus. We used voltage sensitive dye recordings to detect action potential discharge in primary cultures of human myenteric neurons in response to PAR activating peptides (AP. Application of the PAR1-AP (TFLLR or PAR4-AP (GYPGQV evoked spike discharge in 79% or 23% of myenteric neurons, respectively. The PAR1-AP response was mimicked by the endogenous PAR1 activator thrombin and blocked by the PAR1 antagonists SCH79797. Human myenteric neurons did not respond to PAR2-AP. This was not due to culture conditions because all three PAR-APs evoked action potentials in cultured guinea pig myenteric neurons. Consecutive application of PAR-APs revealed coexpression (relative to the population responding to PAR-APs of PAR1/PAR2 in 51%, PAR1/PAR4 in 43% and of PAR2/PAR4 in 29% of guinea pig myenteric neurons. Our study provided further evidence for the prominent role of neuronal PAR1 in the human enteric nervous system.

  18. Increased amplitude of low frequency fluctuations but normal hippocampal-default mode network connectivity in schizophrenia

    Directory of Open Access Journals (Sweden)

    Maureen eMcHugo

    2015-06-01

    Full Text Available Background: Clinical and preclinical studies have established that the hippocampus is hyperactive in schizophrenia, making it a possible biomarker for drug development. Increased hippocampal connectivity, which can be studied conveniently with resting state imaging, has been proposed as a readily accessible corollary of hippocampal hyperactivity. Here we tested the hypothesis that hippocampal activity and connectivity are increased in patients with schizophrenia.Methods: Sixty-three schizophrenia patients and 71 healthy control subjects completed a resting state functional magnetic resonance imaging scan. We assessed hippocampal activity with the amplitude of low frequency fluctuations. We analyzed hippocampal functional connectivity using three common methods: group and single subject level independent component analysis, and seed-based functional connectivity. Results: In patients with schizophrenia, we observed increased amplitude of low frequency fluctuations but normal hippocampal connectivity using independent component and seed-based analyses.Conclusions: Our results indicate that although intrinsic hippocampal activity may be increased in schizophrenia, this finding does not extend to functional connectivity. Neuroimaging methods that directly assess hippocampal activity may be more promising for the identification of a biomarker for schizophrenia.

  19. Hydrogenase activity in aged, nonviable Desulfovibrio vulgaris cultures and its significance in anaerobic biocorrosion.

    Science.gov (United States)

    Chatelus, C; Carrier, P; Saignes, P; Libert, M F; Berlier, Y; Lespinat, P A; Fauque, G; Legall, J

    1987-07-01

    Batch cultures of Desulfovibrio vulgaris stored at 32 degrees C for 10 months have been found to retain 50% of the hydrogenase activity of a 1-day culture. The hydrogenase found in old cultures needs reducing conditions for its activation. Viable cell counts are negative after 6 months, showing that the hydrogenase activity does not depend on the presence of viable cells. These observations are of importance in the understanding of anaerobic biocorrosion of metals caused by depolarization phenomena.

  20. Extracellular enzyme activity in anaerobic bacterial cultures: evidence of pullulanase activity among mesophilic marine bacteria.

    OpenAIRE

    C. Arnosti; Repeta, D. J.

    1994-01-01

    The extracellular enzymatic activity of a mixed culture of anaerobic marine bacteria enriched on pullulan [alpha(1,6)-linked maltotriose units] was directly assessed with a combination of gel permeation chromatography (GPC) and nuclear magnetic resonance spectroscopy (NMR). Hydrolysis products of pullulan were separated by GPC into three fractions with molecular weights of > or = 10,000, approximately 5,000, and < or = 1,200. NMR spectra of these fractions demonstrated that pullulan was rapid...

  1. Ghrelin receptor activity amplifies hippocampal N-methyl-d-aspartate receptor-mediated postsynaptic currents and increases phosphorylation of the GluN1 subunit at Ser896 and Ser897.

    Science.gov (United States)

    Muniz, Brandon G; Isokawa, Masako

    2015-12-01

    Although ghrelin and its cognate receptor growth hormone secretagogue receptor (GHSR1a) are highly localized in the hypothalamic nuclei for the regulation of metabolic states and feeding, GHSR1a is also highly localized in the hippocampus, suggesting its involvement in extra-hypothalamic functions. Indeed, exogenous application of ghrelin has been reported to improve hippocampal learning and memory. However, the underlying mechanism of ghrelin regulation of hippocampal functions is poorly understood. Here, we report ghrelin-promoted phosphorylation of GluN1 and amplified N-methyl-d-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents in the CA1 pyramidal cells of the hippocampus in slice preparations. The ghrelin-induced responses were sensitive to a GHSR1a antagonist and inverse agonist, and were absent in GHSR1a homozygous knock-out mice. These results indicated that activation of GHSR1a was critical in the ghrelin-induced enhancement of the NMDAR function. Interestingly, heterozygous mouse hippocampi were also insensitive to ghrelin treatment, suggesting that a slight reduction in the availability of GHSR1a may be sufficient to negate the effect of ghrelin on GluN1 phosphorylation and NMDAR channel activities. In addition, NMDAR-mediated spike currents, which are of dendritic origin, were blocked by the GHSR1a antagonist, suggesting the presence of GHSR1a on the pyramidal cell dendrites in physical proximity to NMDAR. Together with our findings on the localization of GHSR1a in the CA1 region of the hippocampus, which was shown by fluorescent ghrelin binding, immunoreactivity, and enhanced green fluorescent protein reporter gene expression, we conclude that the activation of GHSR1a favours rapid modulation of the NMDAR-mediated glutamatergic synaptic transmission by phosphorylating GluN1 in the hippocampus. PMID:26490687

  2. Endoplasmic Reticulum Stress-Mediated Hippocampal Neuron Apoptosis Involved in Diabetic Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    2013-01-01

    Full Text Available Poor management of DM causes cognitive impairment while the mechanism is still unconfirmed. The aim of the present study was to investigate the activation of C/EBP Homology Protein (CHOP, the prominent mediator of the endoplasmic reticulum (ER stress-induced apoptosis under hyperglycemia. We employed streptozotocin- (STZ- induced diabetic rats to explore the ability of learning and memory by the Morris water maze test. The ultrastructure of hippocampus in diabetic rats and cultured neurons in high glucose medium were observed by transmission electron microscopy and scanning electron microscopy. TUNEL staining was also performed to assess apoptotic cells while the expression of CHOP was assayed by immunohistochemistry and Western blot assay in these hippocampal neurons. Six weeks after diabetes induction, the escape latency increased and the average frequency in finding the platform decreased in diabetic rats (P<0.05. The morphology of neuron and synaptic structure was impaired; the number of TUNEL-positive cells and the expression of CHOP in hippocampus of diabetic rats and high glucose medium cultured neurons were markedly altered (P<0.05. The present results suggested that the CHOP-dependent endoplasmic reticulum (ER stress-mediated apoptosis may be involved in hyperglycemia-induced hippocampal synapses and neurons impairment and promote the diabetic cognitive impairment.

  3. Hyperpolarization-activated cation current contributes to spontaneous network activity in developing neocortical cultures.

    Science.gov (United States)

    Klueva, Julia; Lima, Ana D de; Meis, Susanne; Voigt, Thomas; Munsch, Thomas

    2012-01-01

    The mechanisms underlying spontaneous burst activity (SBA), appearing in networks of embryonic cortical neurons at the end of the first week in vitro, remain elusive. Here we investigated the contribution of the hyperpolarization-activated cation current (I(h)) to SBA in cortical cultures of GAD67-GFP mice. I(h) current could be detected in GFP-positive large GABAergic interneurons (L-INs) and glutamatergic principal neurons (PNs) as early as DIV 5. Under current-clamp conditions, blockers of I(h) current, ZD7288 and Cs⁺, abolished the voltage sag and rebound depolarization. ZD7288 induced a hyperpolarization concomitant with an increase in the membrane input resistance in L-INs and PNs. Voltage-clamp recordings revealed I(h) as slowly activating inward current with a reversal potential close to -50 mV and a mid-activation point around -90 mV. Both, ZD7288 (1-10 μM) and Cs⁺ (1-2 mM) reduced SBA, spontaneous activity-driven Ca²⁺ transients, and frequency as well as amplitude of miniature GABAergic postsynaptic currents. Immunocytochemistry and Western blot demonstrated that HCN1 and HCN2 were the prevalent isoforms of HCN channels expressed in L-INs and PNs. These results suggest an important contribution of HCN channels to the maintenance of SBA in embryonic cortical cultures. PMID:22094222

  4. Associative reinstatement memory measures hippocampal function in Parkinson's Disease.

    Science.gov (United States)

    Cohn, Melanie; Giannoylis, Irene; De Belder, Maya; Saint-Cyr, Jean A; McAndrews, Mary Pat

    2016-09-01

    In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task - Associative Reinstatement Memory (ARM) - may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD. PMID

  5. NMDA receptors mediate synaptic competition in culture.

    Directory of Open Access Journals (Sweden)

    Kevin She

    Full Text Available BACKGROUND: Activity through NMDA type glutamate receptors sculpts connectivity in the developing nervous system. This topic is typically studied in the visual system in vivo, where activity of inputs can be differentially regulated, but in which individual synapses are difficult to visualize and mechanisms governing synaptic competition can be difficult to ascertain. Here, we develop a model of NMDA-receptor dependent synaptic competition in dissociated cultured hippocampal neurons. METHODOLOGY/PRINCIPAL FINDINGS: GluN1 -/- (KO mouse hippocampal neurons lacking the essential NMDA receptor subunit were cultured alone or cultured in defined ratios with wild type (WT neurons. The absence of functional NMDA receptors did not alter neuron survival. Synapse development was assessed by immunofluorescence for postsynaptic PSD-95 family scaffold and apposed presynaptic vesicular glutamate transporter VGlut1. Synapse density was specifically enhanced onto minority wild type neurons co-cultured with a majority of GluN1 -/- neighbour neurons, both relative to the GluN1 -/- neighbours and relative to sister pure wild type cultures. This form of synaptic competition was dependent on NMDA receptor activity and not conferred by the mere physical presence of GluN1. In contrast to these results in 10% WT and 90% KO co-cultures, synapse density did not differ by genotype in 50% WT and 50% KO co-cultures or in 90% WT and 10% KO co-cultures. CONCLUSIONS/SIGNIFICANCE: The enhanced synaptic density onto NMDA receptor-competent neurons in minority coculture with GluN1 -/- neurons represents a cell culture paradigm for studying synaptic competition. Mechanisms involved may include a retrograde 'reward' signal generated by WT neurons, although in this paradigm there was no 'punishment' signal against GluN1 -/- neurons. Cell culture assays involving such defined circuits may help uncover the rules and mechanisms of activity-dependent synaptic competition in the

  6. Erythropoietin promotes hippocampal neurogenesis in in-vitro models of neonatal stroke

    OpenAIRE

    Osredkar, Damjan; Sall, Jeffrey W; Bickler, Philip E; Ferriero, Donna M.

    2010-01-01

    The hippocampus is often injured in neonatal stroke. We have investigated the effect of erythropoietin (EPO) on oxygen-glucose deprived hippocampal slices and hypoxic progenitor cells. EPO improved survival of the organotypic hippocampal slices with significantly less cell death in the dentate gyrus and an increased number of proliferating cells 4-5 days after insult. Significantly fewer markers of neurogenesis were seen after the insult but when EPO was added to the culture medium, neurogene...

  7. Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis.

    Science.gov (United States)

    Naeve, G S; Ramakrishnan, M; Kramer, R; Hevroni, D; Citri, Y; Theill, L E

    1997-03-18

    Neural activity and neurotrophins induce synaptic remodeling in part by altering gene expression. A cDNA encoding a glycosylphoshatidylinositol-anchored protein was identified by screening for hippocampal genes that are induced by neural activity. This molecule, named neuritin, is expressed in postmitotic-differentiating neurons of the developing nervous system and neuronal structures associated with plasticity in the adult. Neuritin message is induced by neuronal activity and by the activity-regulated neurotrophins BDNF and NT-3. Purified recombinant neuritin promotes neurite outgrowth and arborization in primary embryonic hippocampal and cortical cultures. These data implicate neuritin as a downstream effector of activity-induced neurite outgrowth. PMID:9122250

  8. 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.

  9. Researching Contradictions: Cultural Historical Activity Theory Research (CHAT) in the English Classroom

    Science.gov (United States)

    Thompson, Ian

    2015-01-01

    This article argues that Cultural Historical Activity Theory (CHAT) is an appropriate theoretical and methodological framework for researchers in English interested in the social contexts of culture and its relationship with the formation of mind and activity in the English classroom. Two key concepts in Vygotsky's thought central to understanding…

  10. THE PVN-HIPPOCAMPAL ghrelin NEURONS PROJECTION AND ITS EFFECTS ON ELECTRICAL ACTIVITY OF THE HIPPOCAMPUS%PVN-海马ghrelin神经元投射及对海马电活动影响

    Institute of Scientific and Technical Information of China (English)

    邱贝贝; 徐珞

    2013-01-01

    目的 了解电刺激大鼠下丘脑室旁核(PVN)对海马CA1区ghrelin调控胃扩张(GD)敏感神经元放电活动的影响,初步探讨ghrelin在PVN-海马通路中的调控作用.方法 选用成年Wistar大鼠84只,采用电刺激PVN、核团微量注射及细胞外记录神经元单位放电方法,记录电刺激PVN海马CA1区GD敏感神经元自发放电活动的改变;同时观察海马CA1区给予ghrelin受体阻断剂[D-Lys-3]-GHRP-6,海马CA1区GD敏感神经元放电活动的变化.结果 海马CA1区记录的255个神经元中有120个(47.1%)神经元对GD刺激有反应,其中84个(70.0%)为GD兴奋性(GD-E)神经元,36个(30.0%)为GD抑制性(GD-Ⅰ)神经元.在GD-E神经元中,微量注射ghrelin可兴奋其中53.1%的神经元,与核团注射生理盐水组相比,放电频率显著增加(t=2.686,P<0.05);而在GD-Ⅰ神经元中,微量注射ghrelin后58.3%神经元呈抑制效应,放电频率显著降低(t=3.591,P<0.05),且ghrelin的效应可被其受体阻断剂[D-Lys-3]-GHRP-6完全阻断.对ghrelin有兴奋反应的GD-E神经元,电刺激PVN,其中23.5% GD-E神经元的兴奋效应可被[D-Lys-3]-GHRP-6部分阻断.结论 PVN可调控海马CA1区GD敏感神经元放电活动,在PVN-海马直接或间接通路中ghrelin参与了兴奋传递的调控.%Objective To explore the effects of electrical stimulation of hypothalamic paraventricular nucles (PVN) in rats on the activity of ghrelin regulation of gastric distention (GD) sensitive neurons in the hippocampal CA1 region, and preliminarily study the regulation of ghrelin in the PVN-hippocampal pathway. Methods Eighty-four adult Wistar rats were selected in this experiment. The effects of electrical stimulation of PVN on the activity of GD sensitive neurons in the hippocampal CA1 region were observed by electrical stimulation of PVN, nuclei microinjecion and recording extracellular potentials of single neuron. The changes of the GD sensitive neurons discharge activities in

  11. VTA neurons coordinate with the hippocampal reactivation of spatial experience.

    Science.gov (United States)

    Gomperts, Stephen N; Kloosterman, Fabian; Wilson, Matthew A

    2015-01-01

    Spatial learning requires the hippocampus, and the replay of spatial sequences during hippocampal sharp wave-ripple (SPW-R) events of quiet wakefulness and sleep is believed to play a crucial role. To test whether the coordination of VTA reward prediction error signals with these replayed spatial sequences could contribute to this process, we recorded from neuronal ensembles of the hippocampus and VTA as rats performed appetitive spatial tasks and subsequently slept. We found that many reward responsive (RR) VTA neurons coordinated with quiet wakefulness-associated hippocampal SPW-R events that replayed recent experience. In contrast, coordination between RR neurons and SPW-R events in subsequent slow wave sleep was diminished. Together, these results indicate distinct contributions of VTA reinforcement activity associated with hippocampal spatial replay to the processing of wake and SWS-associated spatial memory. PMID:26465113

  12. Inhibition of Crotalidae venom hemorrhagic activities by Didelphis marsupialis liver spheroids culture supernatants.

    Science.gov (United States)

    Salgueiro, L M; Rodríguez-Acosta, A; Rivas-Vetencourt, P; Zerpa, M; Carillo, G; Aguilar, I; Girón, M E; Acevedo, C E; Gendzekhadze, K

    2001-05-01

    The main aim of this work was the development of a primary hepatocyte culture from Didelphis marsupialis, to determine the possible use of culture medium supernatants as a source of inhibitors of the Bothrops lanceolatus venom hemorrhagic activity. The cellular culture was carried out from isolated hepatocytes by the double perfusion technique, and digestion of the liver with collagenase and culturing the hepatocytes in a liquid media under continuous agitation at 37 degrees C in 5% CO2. The hemorrhagic activity inhibition assays were performed inoculating intradermically, a mixture of Bothrops lanceolatus venom plus a pool of liver spheroids culture supernatants, in mice. These liver Didelphis marsupialis spheroid cultures were adequate to obtain large supernatant volumes with inhibitors of hemorrhagic activity. PMID:11405280

  13. Biilliards, rhythms, collectives - Billiards at a Danish activity center as a culturally specific form of active ageing

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    2014-01-01

    Through an ethnographic study of older men playing billiards at an activity centre and a document study of how the concept of activity has changed during the last 60 years, this article argues that active ageing policies overlook that activities are culturally significant forms of practise situated...

  14. Functional impact of a recently identified quantitative trait locus for hippocampal volume with genome-wide support

    OpenAIRE

    Erk, S.; Meyer-Lindenberg, A; Nöthen, M M; Heinz, A.; Walter, H.; Schmierer, P; Grimm, O.; H. Tost; Mühleisen, T; Mattheisen, M; Seiferth, N.; Cichon, S; Rietschel, M

    2013-01-01

    In a large brain-imaging study, a multinational consortium has recently identified a common genetic variation in rs7294919 being associated with hippocampal volume. Here, we explored whether this quantitative trait locus also affects hippocampal function using a previously established reliable neuroimaging paradigm. We observed a significant effect of rs7294919 variation in the right hippocampus showing that hippocampal activation increased with the number of risk alleles. Furthermore, the ri...

  15. Trafficking of astrocytic vesicles in hippocampal slices

    International Nuclear Information System (INIS)

    The increasingly appreciated role of astrocytes in neurophysiology dictates a thorough understanding of the mechanisms underlying the communication between astrocytes and neurons. In particular, the uptake and release of signaling substances into/from astrocytes is considered as crucial. The release of different gliotransmitters involves regulated exocytosis, consisting of the fusion between the vesicle and the plasma membranes. After fusion with the plasma membrane vesicles may be retrieved into the cytoplasm and may continue to recycle. To study the mobility implicated in the retrieval of secretory vesicles, these structures have been previously efficiently and specifically labeled in cultured astrocytes, by exposing live cells to primary and secondary antibodies. Since the vesicle labeling and the vesicle mobility properties may be an artifact of cell culture conditions, we here asked whether the retrieving exocytotic vesicles can be labeled in brain tissue slices and whether their mobility differs to that observed in cell cultures. We labeled astrocytic vesicles and recorded their mobility with two-photon microscopy in hippocampal slices from transgenic mice with fluorescently tagged astrocytes (GFP mice) and in wild-type mice with astrocytes labeled by Fluo4 fluorescence indicator. Glutamatergic vesicles and peptidergic granules were labeled by the anti-vesicular glutamate transporter 1 (vGlut1) and anti-atrial natriuretic peptide (ANP) antibodies, respectively. We report that the vesicle mobility parameters (velocity, maximal displacement and track length) recorded in astrocytes from tissue slices are similar to those reported previously in cultured astrocytes.

  16. Trafficking of astrocytic vesicles in hippocampal slices

    Energy Technology Data Exchange (ETDEWEB)

    Potokar, Maja; Kreft, Marko [Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, 1000 Ljubljana (Slovenia); Celica Biomedical Center, Technology Park 24, 1000 Ljubljana (Slovenia); Lee, So-Young; Takano, Hajime; Haydon, Philip G. [Department of Neuroscience, Room 215, Stemmler Hall, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 (United States); Zorec, Robert, E-mail: Robert.Zorec@mf.uni-lj.si [Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, 1000 Ljubljana (Slovenia); Celica Biomedical Center, Technology Park 24, 1000 Ljubljana (Slovenia)

    2009-12-25

    The increasingly appreciated role of astrocytes in neurophysiology dictates a thorough understanding of the mechanisms underlying the communication between astrocytes and neurons. In particular, the uptake and release of signaling substances into/from astrocytes is considered as crucial. The release of different gliotransmitters involves regulated exocytosis, consisting of the fusion between the vesicle and the plasma membranes. After fusion with the plasma membrane vesicles may be retrieved into the cytoplasm and may continue to recycle. To study the mobility implicated in the retrieval of secretory vesicles, these structures have been previously efficiently and specifically labeled in cultured astrocytes, by exposing live cells to primary and secondary antibodies. Since the vesicle labeling and the vesicle mobility properties may be an artifact of cell culture conditions, we here asked whether the retrieving exocytotic vesicles can be labeled in brain tissue slices and whether their mobility differs to that observed in cell cultures. We labeled astrocytic vesicles and recorded their mobility with two-photon microscopy in hippocampal slices from transgenic mice with fluorescently tagged astrocytes (GFP mice) and in wild-type mice with astrocytes labeled by Fluo4 fluorescence indicator. Glutamatergic vesicles and peptidergic granules were labeled by the anti-vesicular glutamate transporter 1 (vGlut1) and anti-atrial natriuretic peptide (ANP) antibodies, respectively. We report that the vesicle mobility parameters (velocity, maximal displacement and track length) recorded in astrocytes from tissue slices are similar to those reported previously in cultured astrocytes.

  17. The effect of estrogen synthesis inhibition on hippocampal memory.

    Science.gov (United States)

    Bayer, Janine; Rune, Gabriele; Schultz, Heidrun; Tobia, Michael J; Mebes, Imke; Katzler, Olaf; Sommer, Tobias

    2015-06-01

    17-Beta-estradiol (E2) facilitates long term-potentiation (LTP) and increases spine synapse density in hippocampal neurons of ovariectomized rodents. Consistent with these beneficial effects on the cellular level, E2 improves hippocampus-dependent memory. A prominent approach to study E2 effects in rodents is the inhibition of its synthesis by letrozole, which reduces LTPs and spine synapse density. In the current longitudinal functional magnetic resonance imaging (fMRI) study, we translated this approach to humans and compared the impact of E2 synthesis inhibition on memory performance and hippocampal activity in post-menopausal women taking letrozole (n = 21) to controls (n = 24). In particular, we employed various behavioral memory paradigms that allow the disentanglement of hippocampus-dependent and -independent memory. Consistent with the literature on rodents, E2 synthesis inhibition specifically impaired hippocampus-dependent memory, however, this did not apply to the same degree to all of the employed paradigms. On the neuronal level, E2 depletion tended to decrease hippocampal activity during encoding, whereas it increased activity in the anterior cingulate and the dorsolateral prefrontal cortex. We thus infer that the inhibition of E2 synthesis specifically impairs hippocampal functioning in humans, whereas the increased prefrontal activity presumably reflects a compensatory mechanism, which is already known from studies on cognitive aging and Alzheimer's disease. PMID:25863445

  18. From activity to learning: using cultural historical activity theory to model school library programmes and practices

    Directory of Open Access Journals (Sweden)

    E.M. Meyers

    2007-01-01

    Full Text Available Introduction. changes in educational policy and practice demand that we examine school library programmes from a new perspective. As a model that takes a developmental view of minds in context, Cultural Historical Activity Theory is particularly well suited to the study of school libraries and the learning that occurs therein. This paper focuses on the activity theoretic concepts of 'contradictions' and 'expansive learning' as they relate to the development of best practices. Method. Developmental Work Research was applied as a guiding methodology in an intervention study of six high school libraries in Washington State, USA. Library activity is illustrated from multiple perspectives using a triangulated, qualitative approach. Analysis. contradictions and tensions in the general school library activity system are identified, and an intervention was designed to facilitiate the development of expansive instruments. A case example illustrates a second level of analysis and specific points of intervention. Results. analysis reveals that the tensions and contradictions provide opportunities for expansive learning on the part of the teacher-Librarians. The research team can use practitioners' zones of proximal development to guide the alignment of library programme goals and practices. Conclusion. : some limitations and future promise of the framework and its application are discussed. The proposed activity theory toolkit suggest a new way of exploring the practices of teacher-librarians, incorporating research evidence, professional expertise, and reflective decision making.

  19. Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval

    Science.gov (United States)

    Ishikawa, Rie; Fukushima, Hotaka; Frankland, Paul W; Kida, Satoshi

    2016-01-01

    Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment. DOI: http://dx.doi.org/10.7554/eLife.17464.001

  20. 微波暴露对原代培养大鼠海马神经元热休克蛋白家族表达的影响%Effect of microwave irradiation on expression of heat shock proteins family in primary cultured rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    屈明玥; 邓朝晖; 周舟; 魏爱民; 陈纯海; 余争平; 王登高

    2010-01-01

    目的 研究微波暴露对原代培养大鼠海马神经元中热休克蛋白(heat shock proteins,HSPs)表达调控的影响.方法 采用平均功率密度为90 mW/cm2微波辐照成熟的原代培养大鼠海马神经元10 min,于辐照后0、3、6、12、24 h提取细胞总蛋白,采用免疫印迹(Western blot)法检测HSP27、HSP70、HSP90和热休克转录因子(heat shock factor 1,HSF1)蛋白表达情况;于辐照后0、3、6、12、24 h分别提取细胞总RNA和总蛋白,采用实时定量聚合酶链反应(PCR)检测hsf1的mRNA表达水平;于辐照后20、40 min提取细胞核蛋白,凝胶迁移滞后实验(electrophoretic mobility shift assays,EMSA)法检测HSF1的活性变化.结果 90 mW/cm2微波辐照10 min后,HSP27蛋白表达水平在辐照后3、6、12 h分别明显升高22%、36%、18%,HSP70蛋白表达水平在辐照后3、6、12 h分别明显升高23%、32%、26%,与辐照前比较,差异均有统计学意义(P<0.05,P<0.01).HSP90蛋白表达水平在辐照后6、12 h分别明显升高27%、33%,与辐照前的差异亦有统计学意义(P<0.05,P<0.01).HSF1 mRNA和蛋白表达水平未见明显变化,但微波辐照可激活HSF1的DNA结合活力. 结论微波辐照后大鼠海马神经元发生热休克反应,被活化的HSF1在转录水平上调控HSPs的表达,从而发挥拮抗微波损伤的作用.%Objective To investigate the effects of microwave irradiation on the expression and regulation of heat shock proteins(HSPs)in primary cultured rat hippocampal neurons.Methods Neurons were exposed to 90 mW/cm2 microwave irradiation for 10 minutes.Western blot was used to determine the expression of HSP27, HSP70, HSP90 and heat shock factor 1(HSF1)at 0, 3, 6, 12 and 24 hour respectively.Realtime RT-PCR was used to determine the mRNA expression of HSF1.DNA-binding activity of HSF1 was measured by electrophoretic mobility shift assay(EMSA).Results The protein expression of HSP27 was significantly increased by 22%, 36%, 18% at 3, 6, 12 h

  1. Metabolic activity and enzyme induction in rat fecal microflora maintained in continuous culture.

    OpenAIRE

    Mallett, A K; Bearne, C A; Rowland, I R

    1983-01-01

    The enzyme activity of the rat hindgut microflora maintained in an anaerobic two-stage continuous culture was compared with that of rat cecal contents. A qualitative comparison (API ZYM) showed a high degree of similarity between the two populations. Quantitative determinations showed that azoreductase, beta-glucosidase, nitrate reductase, and nitroreductase activities were comparable, and that beta-glucuronidase activity was very low in the culture. beta-Glucuronidase, beta-glucosidase, and ...

  2. Modeling Impaired Hippocampal Neurogenesis after Radiation Exposure.

    Science.gov (United States)

    Cacao, Eliedonna; Cucinotta, Francis A

    2016-03-01

    Radiation impairment of neurogenesis in the hippocampal dentate gyrus is one of several factors associated with cognitive detriments after treatment of brain cancers in children and adults with radiation therapy. Mouse models have been used to study radiation-induced changes in neurogenesis, however the models are limited in the number of doses, dose fractions, age and time after exposure conditions that have been studied. The purpose of this study is to develop a novel predictive mathematical model of radiation-induced changes to neurogenesis using a system of nonlinear ordinary differential equations (ODEs) to represent the time, age and dose-dependent changes to several cell populations participating in neurogenesis as reported in mouse experiments exposed to low-LET radiation. We considered four compartments to model hippocampal neurogenesis and, consequently, the effects of radiation treatment in altering neurogenesis: (1) neural stem cells (NSCs), (2) neuronal progenitor cells or neuroblasts (NB), (3) immature neurons (ImN) and (4) glioblasts (GB). Because neurogenesis is decreasing with increasing mouse age, a description of the age-related dynamics of hippocampal neurogenesis is considered in the model, which is shown to be an important factor in comparisons to experimental data. A key feature of the model is the description of negative feedback regulation on early and late neuronal proliferation after radiation exposure. The model is augmented with parametric descriptions of the dose and time after irradiation dependences of activation of microglial cells and a possible shift of NSC proliferation from neurogenesis to gliogenesis reported at higher doses (∼10 Gy). Predictions for dose-fractionation regimes and for different mouse ages, and prospects for future work are then discussed. PMID:26943452

  3. Comparison of Hippocampal Volume in Dementia Subtypes

    International Nuclear Information System (INIS)

    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

  4. Antioxidant activity of the organotellurium compound 3-[4-(N,N-dimethylamino)benzenetellurenyl]propanesulfonic acid against oxidative stress in synaptosomal membrane systems and neuronal cultures.

    Science.gov (United States)

    Kanski, J; Drake, J; Aksenova, M; Engman, L; Butterfield, D A

    2001-08-17

    Antioxidant activities of 3-[4-(N,N-dimethylamino) benzenetellurenyl]propanesulfonic acid sodium salt (NDBT) were evaluated in solution, red blood cells, synaptosomal membranes, and cultured hippocampal neuronal cells after exposure to peroxynitrite (ONOO(-)) and hydroxyl radicals. The organotellurium compound NDBT possesses significant activity towards hydrogen peroxide and/or the hydroxyl radical in solution, demonstrated by inhibition of hydroxylation of terephthalic acid. In addition, the compound displayed great antioxidant abilities as shown by: reduction of ONOO(-)-induced 2,7-dichlorofluorescein (DCF) fluorescence in synaptosomes; complete prevention of lipid peroxidation in synaptosomes caused by OH radicals (TBARS), and significant prevention of protein oxidation caused by ONOO(-) and OH, indexed by the levels of protein carbonyls in synaptosomes and neuronal cells. The presence of the compound abolished neuronal cell death caused by ONOO(-). Further, the compound was effective in preventing the oxidative changes in synaptosomal membrane protein conformation and crosslinking (EPR spin labeling). Finally, the organotellurium molecule attenuated peroxynitrite-induced, luminol-dependent chemiluminescence in red blood cells--an index of cellular oxidation. These findings demonstrate the great potential of the antioxidant and are consistent with the notion that NDBT may have a role to play in modulating oxidative stress in neurodegenerative disorders, including Alzheimer's disease.

  5. Antioxidant Activity of Peptides from Fermented Milk with Mix Culture of Lactic Acid Bacteria and Yeast

    Directory of Open Access Journals (Sweden)

    Yun Li

    2015-02-01

    Full Text Available The aim of the present study is to investigate the production of antioxidant peptides during milk fermentation with co-culture of Lactic Acid Bacteria (LAB and yeast. Five LAB strains, previously screened with higher hydrolysis activity and Debaryomyces hansenii H2 which isolated from Tibet kefir were used in the study. The peptides separated from fermented milk were analysed antioxidant activity with DPPH radical scavenging, hydroxyl radical scavenging, chelation of metal ions and reducing power assays. The growth of Streptococcus. thermophilus Lactobacillus. delbrueckii ssp. bulgaricus and Lactococcus. lactis was enhanced with co-cultures and L. acidophilus was inhibited in co-culture with yeast. In co-culture with yeast, a significant decrease of the acidity was observed among all the fermentation and the pH reached higher values than in single LAB cultures. Except for L.delbrueckii ssp. bulgaricus, there was no significant difference of protein hydrolysis with other test LAB strains between co-culture and single culture. The co-incubation of LAB with the yeast developed a stronger antioxidant activity in DPPH radical and hydroxyl radical scavenging and no significant (p>0.05 difference in chelation of metal ions. The reducing power of L.delbrueckii ssp. bulgaricus and L. helveticus in co-culture was significant higher than those of single culture.

  6. Isoflurane-induced neuronal apoptosis in developing hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Hongliang Liu; Tijun Dai; Weitao Guo

    2013-01-01

    We hypothesized that the P2X7 receptor may be the target of isoflurane, so we investigated the roles of the P2X7 receptor and inositol triphosphate receptor in calcium overload and neuronal apoptosis induced by isoflurane in cultured embryonic rat hippocampal neurons. Results showed that isoflurane induced widespread neuronal apoptosis and significantly increased cytoplasmic Ca2+. Blockade of P2X7 receptors or removal of extracellular Ca2+ combined with blockade of inositol triphosphate receptors completely inhibited apoptosis or increase in cytoplasmic Ca2+. Removal of extracellular Ca2+ or blockade of inositol triphosphate receptor alone could partly inhibit these effects of isoflurane. Isoflurane could directly activate P2X7-gated channels and induce inward currents, but did not affect the expression of P2X7 receptor protein in neurons. These findings indicate that the mechanism by which isoflurane induced neuronal apoptosis in rat developing brain was mediated by intracellular calcium overload, which was caused by P2X7 receptor mediated calcium influx and inositol triphosphate receptor mediated calcium release.

  7. Formation and action of oxygen activated species in cell cultures

    International Nuclear Information System (INIS)

    The differences of hydrogen peroxide sensibility of mammal cell lineages (man, mouse, chinese hamster) in culture are studied. The cellular survival and the frequency of DNA induced breaks by hydrogen peroxide are analysed. The efficiency of elimination of DNA breaks by cells is determined. The possible relation between the cell capacity of repair and its survival to hydrogen peroxide action is also discussed. (M.A.)

  8. Building a culture of motor activity in students of secondary schools

    Directory of Open Access Journals (Sweden)

    Vasil’ Sutula

    2015-12-01

    Full Text Available Purpose: to justify the connection and the sequence of the process of formation of culture of motor activity at pupils of elementary and primary schools and to define the role of means of the main gymnastics. Material and Methods: the analysis and synthesis of scientific and methodical literature on use of the main gym in building a culture of motor activity in primary and secondary schools. Results: showed that the concept of "culture of movement" is used only in primary school; it is the first step in creating the culture of motor activity of schoolchildren. The development of pupils motor activity culture is not provided as the main task of the secondary school. Teaching material for pupils of the fifth-ninth grade is not accompanied by a continuation of the formation of their culture of motor activity. Conclusions: the use of basic exercises in creating a culture of pupils motor activity of the primary school is a continuation of "movement school" formed in elementary school

  9. 磁刺激对小鼠海马原代神经元即刻早期基因和细胞骨架蛋白表达的影响%Influence of magnetic stimulation on the expression of immediate early genes and cytoskeletal protein in primary cultured mouse hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    张展翅; 马隽; 栾峰; 康林; 苏玉红; 王彦永; 王铭维; 崔慧先

    2012-01-01

    Objective:To observe the effects of magnetic stimulation on the expression of c-fos, activity regulated cytoskeletal protein, microtubule-associated protein 2 and neurite growth in primary cultured mouse hippocampal neurons, and to explore the possible mechanism of magnetic stimulation on cell neurite growth. Methods:The primary cultured hippocampal neurons were divided into five groups: control group, sham group, 20% maximum stimulus intensity group (20% intensity), 30% maximum stimulus intensity group (30% intensity), and 40% maximum stimulus intensity group (40% intensity). The neurons were stimulated at a rate of 1 Hz after 24h, and the maximum output intensity of magnetic field was 3. 7 Tesla. Continuous stimulation for 5d, the stimulation coil was held paralleled 1 cm above the dish. Cellular immunofluorescence staining was executed immediately in the fifth day after stimulation; the immunofluorescence intensity of c-fos, Arc and MAP2-positive neurons was detected, and the multiple neurites neurons and the cell neurite length of MAP2 positive neurons were counted. Meanwhile, semiquantitative RT-PCR and Western blotting were applied to verify the results. Results:The percentage of multiple neurites neurons(n≥2)and the cell neurite length in each stimulation group was significantly higher than that in the control group. Meanwhile, it was higher in the 30% intensity group than that in 20% and 40% intensity groups, and there was significant difference in the results. C-fos positive neurons proportion and the immunofluorescence intensity of Arc and MAP2 in the 30% intensity group was significantly higher than that in the related control group. The results of Western blotting and RT-PCR were consistent with the immunofluorescence. Conclusion: Magnetic stimulation can promote the neurite outgrowth of primary cultured hippocampus neuron, and the mechanism may be related to the up-regulation of c-fos, Arc and MAP2.%目的:观察磁刺激对小鼠海马原代神经

  10. Geniposide, the component of the Chinese herbal formula Tongluojiunao, protects amyloid-βpeptide (1-42)-mediated death of hippocampal neurons via the non-classical estrogen signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Jiao Li; Yan Tan; Qi Zhang; Xu Wang; Angran Fan; Qian Hua; Feng Wang; Haimin Ding; Chunyan Jin; Jinyan Chen; Yanan Zhao; Xiaojing Li; Wenju Chen; Ping Sun

    2014-01-01

    Tongluojiunao (TLJN) is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1-42 (10 µmol/L) signiifcantly increased the release of lactate dehydroge-nase, which was markedly reduced by TLJN (2 µL/mL), speciifcally by the component geniposide (26 µmol/L), but not ginsenoside Rg1 (2.5 µmol/L). hTe estrogen receptor inhibitor, ICI182780 (1 µmol/L), did not block TLJN-or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 (50 µmol/L) or U0126 (10 µmol/L), respectively blo cked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. hTerefore, these results suggest that the non-classical estrogen pathway (i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase) is involved in the neuroprotective effect of TLJN, speciifcally its component, geniposide, against Aβ1-42-mediated cell death in primary cultured hippocampal neurons.

  11. Modernity, the Individual, and the Foundations of Cultural-Historical Activity Theory

    Science.gov (United States)

    Blunden, Andy

    2007-01-01

    It is argued that the problem of individual agency in relation to social institutions can be resolved within Cultural-Historical Activity Theory (CHAT) by the use of the "subject" as a unit of analysis. Such an approach implies a reaffirmation of the fundamental tenets of CHAT but also a critique of the concepts of society and culture, which are…

  12. Students' Evaluation of Google Hangouts through a Cross-Cultural Group Discussion Activity

    Science.gov (United States)

    Kobayashi, Michiko

    2015-01-01

    The study investigated perceived ease of use and usefulness of Google Hangouts as an instructional/learning tool. Forty-two teacher education students at U.S and Japanese universities participated in an online cross-cultural activity using Google Hangouts and discussed cultural differences between the two countries and their teaching philosophies.…

  13. Spatiotemporal stability of neonatal rat cardiomyocyte monolayers spontaneous activity is dependent on the culture substrate.

    Directory of Open Access Journals (Sweden)

    Jonathan Boudreau-Béland

    Full Text Available In native conditions, cardiac cells must continuously comply with diverse stimuli necessitating a perpetual adaptation. Polydimethylsiloxane (PDMS is commonly used in cell culture to study cellular response to changes in the mechanical environment. The aim of this study was to evaluate the impact of using PDMS substrates on the properties of spontaneous activity of cardiomyocyte monolayer cultures. We compared PDMS to the gold standard normally used in culture: a glass substrate. Although mean frequency of spontaneous activity remained unaltered, incidence of reentrant activity was significantly higher in samples cultured on glass compared to PDMS substrates. Higher spatial and temporal instability of the spontaneous rate activation was found when cardiomyocytes were cultured on PDMS, and correlated with decreased connexin-43 and increased CaV3.1 and HCN2 mRNA levels. Compared to cultures on glass, cultures on PDMS were associated with the strongest response to isoproterenol and acetylcholine. These results reveal the importance of carefully selecting the culture substrate for studies involving mechanical stimulation, especially for tissue engineering or pharmacological high-throughput screening of cardiac tissue analog.

  14. Accessible cultural mind-set modulates default mode activity: evidence for the culturally situated brain.

    Science.gov (United States)

    Wang, Chenbo; Oyserman, Daphna; Liu, Qiang; Li, Hong; Han, Shihui

    2013-01-01

    Self-construal priming modulates human behavior and associated neural activity. However, the neural activity associated with the self-construal priming procedure itself remains unknown. It is also unclear whether and how self-construal priming affects neural activity prior to engaging in a particular task. To address this gap, we scanned Chinese adults, using functional magnetic resonance imaging, during self-construal priming and a following resting state. We found that, relative to a calculation task, both interdependent and independent self-construal priming activated the ventral medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC). The contrast of interdependent vs. independent self-construal priming also revealed increased activity in the dorsal MPFC and left middle frontal cortex. The regional homogeneity analysis of the resting-state activity revealed increased local synchronization of spontaneous activity in the dorsal MPFC but decreased local synchronization of spontaneous activity in the PCC when contrasting interdependent vs. independent self-construal priming. The functional connectivity analysis of the resting-state activity, however, did not show significant difference in synchronization of activities in remote brain regions between different priming conditions. Our findings suggest that accessible collectivistic/individualistic mind-set induced by self-construal priming is associated with modulations of both task-related and resting-state activity in the default mode network.

  15. Hippocampal sleep features: relations to human memory function

    Directory of Open Access Journals (Sweden)

    Michele eFerrara

    2012-04-01

    Full Text Available The recent spread of intracranial EEG recordings techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific pattern of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, NREM sleep in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate sleep

  16. Activated Sludge and other Aerobic Suspended Culture Processes.

    Science.gov (United States)

    Li, Chunying; Wei, Li; Chang, Chein-Chi; Zhang, Yuhua; Wei, Dong

    2016-10-01

    This is a literature review for the year 2015 and contains information specifically associated with suspended growth processes including activated sludge, upflow anaerobic sludge blanket, and sequencing batch reactors. The review encompasses modeling and kinetics, nutrient removal, system design and operation. Compared to past reviews, many topics show increase in activity in 2015. These include, fate and effect of xenobiotics, industrial wastes treatment with sludge, and pretreatment for the activated sludge. These topics are referred to the degradation of constituents in activated sludge. Other sections include population dynamics, process microbiology give an insight into the activated sludge. The subsection in industrial wastes: converting sewage sludge into biogases was also mentioned. PMID:27620082

  17. 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.

  18. The role of food culture and marketing activity in health disparities.

    Science.gov (United States)

    Williams, Jerome D; Crockett, David; Harrison, Robert L; Thomas, Kevin D

    2012-11-01

    Marketing activities have attracted increased attention from scholars interested in racial disparities in obesity prevalence, as well as the prevalence of other preventable conditions. Although reducing the marketing of nutritionally poor foods to racial/ethnic communities would represent a significant step forward in eliminating racial disparities in health, we focus instead on a critical-related question. What is the relationship between marketing activities, food culture, and health disparities? This commentary posits that food culture shapes the demand for food and the meaning attached to particular foods, preparation styles, and eating practices, while marketing activities shape the overall environment in which food choices are made. We build on prior research that explores the socio-cultural context in which marketing efforts are perceived and interpreted. We discuss each element of the marketing mix to highlight the complex relationship between food culture, marketing activities, and health disparities.

  19. The role of food culture and marketing activity in health disparities.

    Science.gov (United States)

    Williams, Jerome D; Crockett, David; Harrison, Robert L; Thomas, Kevin D

    2012-11-01

    Marketing activities have attracted increased attention from scholars interested in racial disparities in obesity prevalence, as well as the prevalence of other preventable conditions. Although reducing the marketing of nutritionally poor foods to racial/ethnic communities would represent a significant step forward in eliminating racial disparities in health, we focus instead on a critical-related question. What is the relationship between marketing activities, food culture, and health disparities? This commentary posits that food culture shapes the demand for food and the meaning attached to particular foods, preparation styles, and eating practices, while marketing activities shape the overall environment in which food choices are made. We build on prior research that explores the socio-cultural context in which marketing efforts are perceived and interpreted. We discuss each element of the marketing mix to highlight the complex relationship between food culture, marketing activities, and health disparities. PMID:22227280

  20. The Impact of the Campus Culture on Students' Civic Activities, Values, and Beliefs

    Science.gov (United States)

    Billings, Meredith S.; Terkla, Dawn Geronimo

    2014-01-01

    A supportive campus culture is critical to institutionalizing civic engagement and instilling the principles of active citizenship. This chapter explores a model that quantitatively measures the impact of the campus environment on civic engagement outcomes.

  1. Immunologically active polysaccharides of Arnica montana cell cultures.

    Science.gov (United States)

    Puhlmann, J; Zenk, M H; Wagner, H

    1991-01-01

    From the nutrition medium of Arnica montana cell cultures two homogeneous polysaccharides, an acidic arabino-3,6-galactan-protein with mean Mr of 100,000 and a neutral fucogalactoxyloglucan with mean Mr of 22,500 have been isolated by DEAE-Sepharose CL-6B and Sephacryl S-400 column chromatography. Their structures were elucidated mainly by methylation analysis, partial acidic and enzymatic hydrolysis and 13C NMR spectroscopy. The fucogalactoxyloglucan shows a pronounced enhancement of phagocytosis in vivo. The arabino-3,6-galactan-protein displays a strong anticomplementary effect and stimulates macrophages to excrete the tumour necrosis factor (TNF alpha).

  2. Long-Term Exposure to High Corticosterone Levels Inducing a Decrease of Adenylate Kinase 1 Activity

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yu'nan; SHEN Jia; SU Hui; HUANG Yufang; XING Dongming; DU Lijun

    2009-01-01

    Corticosterone, a principal glucocorticoid synthesized in the rodent adrenal cortex, can be cumula-tively toxic to hippocampal neurons, the cause of which is not known. The present study determined whether the cytosol adenylate kinase (AK) system was involved in the neuronal damage induced by long-term exposure to high corticosterone levels. We investigated the effects of long-term exposure to high corticosterone levels on AK1 activity, AK1 mRNA expression, and energy levels in cultured hippocampal neurons. The results show that long-term exposure to high corticosterone levels induces a reduction of the cultured hippocampal neuron viability, significantly reduces energy levels, and causes a time-dependant re-duction of the AK1 activity. These findings indicate that changes in the AK system might be the mechanism underlying neuronal damage induced by long-term exposure to high corticosterone levels.

  3. Physiological and Pedagogical Culture as a Basic for Effective Teaching Activity

    Directory of Open Access Journals (Sweden)

    Pirmagambet Z. Ishanov

    2014-07-01

    Full Text Available The article deals with new approaches to organization of pedagogical education of a teacher in institutions of higher learning. Here we consider cult urological, personal, multiobjective (dialogic and individual-creative approaches. In this case, pedagogical activity is considered as a form of active correlation to the world, transformation experience of culture into pedagogue’s professional wealth. So, one of the factors determining the university teacher’s effectiveness is his psycho-pedagogical culture.

  4. Understanding Synchronous Computer-Mediated Classroom Discussion through Cultural-Historical Activity Theory

    Science.gov (United States)

    Park, Yangjoo

    2015-01-01

    This study is about graduate students' discourse practices in classroom text-based synchronous computer mediated discussions (SCMD). Cultural historical activity theory (in short, Activity Theory) is the primary theoretical lens through which the data are analyzed. Engeström's (1987) Activity System model among the various theoretical positions or…

  5. Inhibitory effect of mycoplasma-released arginase. Activity in mixed-lymphocyte and tumour cell cultures

    DEFF Research Database (Denmark)

    Claesson, M H; Tscherning, T; Nissen, Mogens Holst;

    1990-01-01

    Non-fermenting mycoplasma species deplete culture media for arginine through arginase activity linked to their arginine deiminase pathway, resulting in proliferation arrest and cell death in mycoplasma-contaminated cell cultures. The presence of only 2-3 Mycoplasma (M.) arginini-contaminated T...... assayed in MLC and cell proliferation culture. SDS-PAGE followed by western blotting and reaction with antisera raised against non-fermenting mycoplasma species demonstrated a band at 43 kDa common for these micro-organisms....... cells in a one-way allogeneic mixed-lymphocyte culture (MLC) significantly inhibits development of cytotoxic T-cell activity. Likewise, strong degrees of inhibition are observed after addition of nanogram doses of M. arginini extracts (MAE) to MLC or cell proliferation cultures. M. arginini-induced cell...

  6. Effects of calcium channel on 3-morpholinosydnonimine-induced rat hippocampal neuronal apoptosis

    Institute of Scientific and Technical Information of China (English)

    Quanzhong Chang; Shuling Zhang; Yuanyin Zheng; Lijuan Xu; Jinbao Yin; Shining Cai

    2011-01-01

    Previous studies have demonstrated that increased chloride channel activity plays a role in nitric oxide-induced neuronal apoptosis in the rat hippocampus.The present study investigated the effects of the broad-spectrum calcium channel blocker CdC12 on survival rate, percentage of apoptosis, and morphological changes in hippocampal neurons cultured in vitro, as well as the effects of calcium channels on neuronal apoptosis.The chloride channel blockers 4-acetamido-4'-isothiocyanatostilbene-2, 2'-disulfonic acid (SITS) or 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) increased the survival rate of 3-morpholinosydnonimine (SIN-1)-treated neurons and suppressed SIN-1-induced neuronal apoptosis.The calcium channel blocker CdC12 did not increase the survival rate of neurons and did not affect SIN-1-induced apoptosis or SITS- or DIDS-suppressed neuronal apoptosis.Results demonstrated that calcium channels did not significantly affect neuronal apoptosis.

  7. The Edible Red Alga Porphyra yezoensis Promotes Neuronal Survival and Cytoarchitecture in Primary Hippocampal Neurons.

    Science.gov (United States)

    Mohibbullah, Md; Bhuiyan, Mohammad Maqueshudul Haque; Hannan, Md Abdul; Getachew, Paulos; Hong, Yong-Ki; Choi, Jae-Suk; Choi, In Soon; Moon, Il Soo

    2016-07-01

    The edible red alga Porphyra yezoensis is among the most popular marine algae and is of economic and medicinal importance. In the present study, the neurotrophic and neuroprotective activities of the ethanol extract of P. yezoensis (PYE) were investigated in primary cultures of hippocampal neurons. Results revealed that PYE significantly increased neurite outgrowth at an optimal concentration of 15 µg/mL. PYE dose-dependently increased viable cells, significantly accelerated the rate of neuronal differentiation in cultures, promoted axodendritic arborization, and eventually induced synaptogenesis. In addition to morphological development, PYE also promoted functional maturation as indicated by the staining of live cultures with FM 1-43. Moreover, PYE increased neuronal survivability, which was attributed to reduced apoptosis and its ROS scavenging activity. Taurine, a major organic acid in PYE (2.584/100 mg of dry PYE) promoted neurite outgrowth in a dose-dependent manner, and this promotion was suppressed by the taurine antagonist isethionic acid. The study indicates that PYE and its active component, taurine, facilitate neuronal development and maturation and have a neuroprotective effect. PMID:26259718

  8. Physical Exercise Leads to Rapid Adaptations in Hippocampal Vasculature : Temporal Dynamics and Relationship to Cell Proliferation and Neurogenesis

    NARCIS (Netherlands)

    Van der Borght, Karin; Kobor-Nyakas, Dora E.; Klauke, Karin; Eggen, Bart J. L.; Nyakas, Csaba; Van der Zee, Eddy A.; Meerlo, Peter

    2009-01-01

    Increased levels of angiogenesis and neurogenesis possibly mediate the beneficial effects of physical activity on hippocampal plasticity. This study was designed to investigate the temporal dynamics of exercise-induced changes in hippocampal angiogenesis and cell proliferation. Mice were housed with

  9. Differences in activity profile of bacterial cultures studied by dynamic speckle patterns

    Science.gov (United States)

    Ramírez-Miquet, E. E.; Otero, I.; Rodríguez, D.; Darias, J. G.; Combarro, A. M.; Contreras, O. R.

    2013-02-01

    We outline the main differences in the activity profile of bacterial cultures studied by dynamic laser speckle (or biospeckle) patterns. The activity is detected in two sorts of culture mediums. The optical setup and the experimental procedure are presented. The experimentally obtained images are processed by the temporal difference method and a qualitative assessment is made with the time history of speckle patterns of the sample. The main differences are studied after changing the culture medium composition. We conclude that the EC medium is suitable to detect the E. coli bacterial presence in early hours and that Mueller Hinton agar delays some additional hours to make possible the assessment of bacteria in time.

  10. Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

    Directory of Open Access Journals (Sweden)

    Caitlin M. Vander Weele

    2013-06-01

    Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

  11. cultural

    Directory of Open Access Journals (Sweden)

    Irene Kreutz

    2006-01-01

    Full Text Available Es un estudio cualitativo que adoptó como referencial teorico-motodológico la antropología y la etnografía. Presenta las experiencias vivenciadas por mujeres de una comunidad en el proceso salud-enfermedad, con el objetivo de comprender los determinantes sócio-culturales e históricos de las prácticas de prevención y tratamiento adoptados por el grupo cultural por medio de la entrevista semi-estructurada. Los temas que emergieron fueron: la relación entre la alimentación y lo proceso salud-enfermedad, las relaciones con el sistema de salud oficial y el proceso salud-enfermedad y lo sobrenatural. Los dados revelaron que los moradores de la comunidad investigada tienen un modo particular de explicar sus procedimientos terapéuticos. Consideramos que es papel de los profesionales de la salud en sus prácticas, la adopción de abordajes o enfoques que consideren al individuo en su dimensión sócio-cultural e histórica, considerando la enorme diversidad cultural en nuestro país.

  12. The maximum specific hydrogen-producing activity of anaerobic mixed cultures: definition and determination

    Science.gov (United States)

    Mu, Yang; Yang, Hou-Yun; Wang, Ya-Zhou; He, Chuan-Shu; Zhao, Quan-Bao; Wang, Yi; Yu, Han-Qing

    2014-06-01

    Fermentative hydrogen production from wastes has many advantages compared to various chemical methods. Methodology for characterizing the hydrogen-producing activity of anaerobic mixed cultures is essential for monitoring reactor operation in fermentative hydrogen production, however there is lack of such kind of standardized methodologies. In the present study, a new index, i.e., the maximum specific hydrogen-producing activity (SHAm) of anaerobic mixed cultures, was proposed, and consequently a reliable and simple method, named SHAm test, was developed to determine it. Furthermore, the influences of various parameters on the SHAm value determination of anaerobic mixed cultures were evaluated. Additionally, this SHAm assay was tested for different types of substrates and bacterial inocula. Our results demonstrate that this novel SHAm assay was a rapid, accurate and simple methodology for determining the hydrogen-producing activity of anaerobic mixed cultures. Thus, application of this approach is beneficial to establishing a stable anaerobic hydrogen-producing system.

  13. Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons.

    Directory of Open Access Journals (Sweden)

    Fumiaki Fukushima

    Full Text Available Synchronized discharges in the hippocampal CA3 recurrent network are supposed to underlie network oscillations, memory formation and seizure generation. In the hippocampal CA3 network, NMDA receptors are abundant at the recurrent synapses but scarce at the mossy fiber synapses. We generated mutant mice in which NMDA receptors were abolished in hippocampal CA3 pyramidal neurons by postnatal day 14. The histological and cytological organizations of the hippocampal CA3 region were indistinguishable between control and mutant mice. We found that mutant mice lacking NMDA receptors selectively in CA3 pyramidal neurons became more susceptible to kainate-induced seizures. Consistently, mutant mice showed characteristic large EEG spikes associated with multiple unit activities (MUA, suggesting enhanced synchronous firing of CA3 neurons. The electrophysiological balance between fast excitatory and inhibitory synaptic transmission was comparable between control and mutant pyramidal neurons in the hippocampal CA3 region, while the NMDA receptor-slow AHP coupling was diminished in the mutant neurons. In the adult brain, inducible ablation of NMDA receptors in the hippocampal CA3 region by the viral expression vector for Cre recombinase also induced similar large EEG spikes. Furthermore, pharmacological blockade of CA3 NMDA receptors enhanced the susceptibility to kainate-induced seizures. These results raise an intriguing possibility that hippocampal CA3 NMDA receptors may suppress the excitability of the recurrent network as a whole in vivo by restricting synchronous firing of CA3 neurons.

  14. Neuronal modulation of calcium channel activity in cultured rat astrocytes.

    OpenAIRE

    Corvalan, V; Cole, R; de Vellis, J.; Hagiwara, S.

    1990-01-01

    The patch-clamp technique was used to study whether cocultivation of neurons and astrocytes modulates the expression of calcium channel activity in astrocytes. Whole-cell patch-clamp recordings from rat brain astrocytes cocultured with rat embryonic neurons revealed two types of voltage-dependent inward currents carried by Ca2+ and blocked by either Cd2+ or Co2+ that otherwise were not detected in purified astrocytes. This expression of calcium channel activity in astrocytes was neuron depend...

  15. Modeling hippocampal neurogenesis using human pluripotent stem cells.

    Science.gov (United States)

    Yu, Diana Xuan; Di Giorgio, Francesco Paolo; Yao, Jun; Marchetto, Maria Carolina; Brennand, Kristen; Wright, Rebecca; Mei, Arianna; McHenry, Lauren; Lisuk, David; Grasmick, Jaeson Michael; Silberman, Pedro; Silberman, Giovanna; Jappelli, Roberto; Gage, Fred H

    2014-03-11

    The availability of human pluripotent stem cells (hPSCs) offers the opportunity to generate lineage-specific cells to investigate mechanisms of human diseases specific to brain regions. Here, we report a differentiation paradigm for hPSCs that enriches for hippocampal dentate gyrus (DG) granule neurons. This differentiation paradigm recapitulates the expression patterns of key developmental genes during hippocampal neurogenesis, exhibits characteristics of neuronal network maturation, and produces PROX1+ neurons that functionally integrate into the DG. Because hippocampal neurogenesis has been implicated in schizophrenia (SCZD), we applied our protocol to SCZD patient-derived human induced pluripotent stem cells (hiPSCs). We found deficits in the generation of DG granule neurons from SCZD hiPSC-derived hippocampal NPCs with lowered levels of NEUROD1, PROX1, and TBR1, reduced neuronal activity, and reduced levels of spontaneous neurotransmitter release. Our approach offers important insights into the neurodevelopmental aspects of SCZD and may be a promising tool for drug screening and personalized medicine.

  16. Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Diana Xuan Yu

    2014-03-01

    Full Text Available The availability of human pluripotent stem cells (hPSCs offers the opportunity to generate lineage-specific cells to investigate mechanisms of human diseases specific to brain regions. Here, we report a differentiation paradigm for hPSCs that enriches for hippocampal dentate gyrus (DG granule neurons. This differentiation paradigm recapitulates the expression patterns of key developmental genes during hippocampal neurogenesis, exhibits characteristics of neuronal network maturation, and produces PROX1+ neurons that functionally integrate into the DG. Because hippocampal neurogenesis has been implicated in schizophrenia (SCZD, we applied our protocol to SCZD patient-derived human induced pluripotent stem cells (hiPSCs. We found deficits in the generation of DG granule neurons from SCZD hiPSC-derived hippocampal NPCs with lowered levels of NEUROD1, PROX1, and TBR1, reduced neuronal activity, and reduced levels of spontaneous neurotransmitter release. Our approach offers important insights into the neurodevelopmental aspects of SCZD and may be a promising tool for drug screening and personalized medicine.

  17. Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2014-01-01

    Full Text Available Tumor necrosis factor-α (TNF-α is a critical proinflammatory cytokine regulating neuroinflammation. Elevated levels of TNF-α have been associated with various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, the signaling events that lead to TNF-α-initiated neurotoxicity are still unclear. Here, we report that RIP3-mediated necroptosis, a form of regulated necrosis, is activated in the mouse hippocampus after intracerebroventricular injection of TNF-α. RIP3 deficiency attenuates TNF-α-initiated loss of hippocampal neurons. Furthermore, we characterized the molecular mechanism of TNF-α-induced neurotoxicity in HT-22 hippocampal neuronal cells. HT-22 cells are sensitive to TNF-α only upon caspase blockage and subsequently undergo necrosis. The cell death is suppressed by knockdown of CYLD or RIP1 or RIP3 or MLKL, suggesting that this necrosis is necroptosis and mediated by CYLD-RIP1-RIP3-MLKL signaling pathway. TNF-α-induced necroptosis of HT-22 cells is largely independent of both ROS accumulation and calcium influx although these events have been shown to be critical for necroptosis in certain cell lines. Taken together, these data not only provide the first in vivo evidence for a role of RIP3 in TNF-α-induced toxicity of hippocampal neurons, but also demonstrate that TNF-α promotes CYLD-RIP1-RIP3-MLKL-mediated necroptosis of hippocampal neurons largely bypassing ROS accumulation and calcium influx.

  18. Hippocampal Sclerosis in Temporal Lobe Epilepsy: Findings at 7 T

    OpenAIRE

    Henry, Thomas R.; Chupin, Marie; Lehéricy, Stéphane; Strupp, John P.; Sikora, Michael A.; Sha, Zhiyi Y.; Uğurbil, Kâmil; Van de Moortele, Pierre-François

    2011-01-01

    Use of 7-T MR imaging might enable us to fully define a wide range of macroscopically visible findings in patients with hippocampal sclerosis, including atrophy of hippocampal subregions and deformities of the hippocampal head and body.

  19. Neuro-protective effects of CNTF on hippocampal neurons via an unknown signal transduction pathway

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In our previous study, we proposed that there may be an unknown pathway in the upper stream of the known signal transduction pathway of Ciliary neurotrophic factor (CNTF) that mediates the neuro-protective function of CNTF. In the present experiment, we observed that the neuro-protective function of the non-classic signal transduction pathway in a L-NMDA (a glutamic acid ion type receptor atagonist) induced hippocampal neuron injury model, using primary culture rat hippocampal neurons, continuous photography and gp130 immunohistochemical assay. The results showed that L-NMDA induced injurious reaction of hippocampal neurons, and CNTF was able to inhibit the toxic action of L-NMDA on hippocampal neurons. Additionally, when JAK/STATs in the known classic signal transduction pathway of CNTF were blocked by PTPi-2, the protective effect of CNTF against L-NMDA injury still existed. L-NMDA caused a rapid increase in the concentration of hippocampal intracellular free [Ca2+]i. CNTF was able to attenuate L-NMDA-induced elevation of [Ca2+]i, and blocking JAK/STATs in the known classic signal trans- duction pathway of CNTF did not affect L-NMDA- induced elevation of [Ca2+]i, indicating that, apart from the known classic signal transduction pathway, there may be some other transduction pathways for CNTF to exert the protective effect on hippocampal neurons, and this pathway is related to [Ca2+].

  20. Glutathione peroxidase activity in cell cultures from differentregions of human epididymis

    Institute of Scientific and Technical Information of China (English)

    Enrique Castellón; Hernán Rioseco; Juan Rojas; Michel Royer; Eduardo Salas; Héctor Contreras; Christian Huidobro

    2005-01-01

    Aim: To study the secretory activity and androgen regulation of glutathione peroxidase (GPx) in epithelial cell cultures from human epididymis. Methods: Tissue was obtained from patients undergoing therapeutic orchidectomy for prostatic cancer. Epithelial cell cultures were obtained from the caput, corpus and cauda epididymides. Enzymatic activity was measured in conditioned media by colorimetric methods in absence or presence of 1, 10 or 100 nmol.L-1from corpus and cauda than caput epididymidis. The presence of different concentrations of testosterone increase enzyme activity in cell cultures from all epididymal regions. Addition of flutamide reverses the androgen dependent increase of GPx activity. Conclusion: GPx activity is secreted from human epididymal cells in a region dependent manner and is regulated by androgens.

  1. Chronic stimulation of cultured neuronal networks boosts low frequency oscillatory activity at theta and gamma with spikes phase-locked to gamma frequencies

    OpenAIRE

    Leondopulos, Stathis S.; Boehler, Michael D.; Wheeler, Bruce C.; Brewer, Gregory J.

    2012-01-01

    Slow wave oscillations in the brain are essential for coordinated network activity but have not been shown to self-organize in vitro. Here, the development of dissociated hippocampal neurons into an active network with oscillations on multi-electrode arrays was evaluated in the absence and presence of chronic external stimulation. Significant changes in signal power were observed in the range of 1-400 Hz with an increase in amplitude during bursts. Stimulation increased oscillatory activity p...

  2. Hippocampal deep brain stimulation reverses physiological and behavioural deficits in a rodent model of schizophrenia.

    Science.gov (United States)

    Perez, Stephanie M; Shah, Amiksha; Asher, Amber; Lodge, Daniel J

    2013-07-01

    Subcortical dopamine system dysregulation has been suggested to underlie the positive symptoms of schizophrenia. Recent preclinical investigations and human imaging studies have proposed that the augmented dopamine system function observed in schizophrenia patients may be secondary to aberrant hippocampal activity. Thus, we posit that the hippocampus represents a novel therapeutic target for the treatment of schizophrenia. Here we provide evidence of the effectiveness of a unique approach aimed at decreasing hippocampal function in a rodent model of schizophrenia. Specifically, in a rodent model of schizophrenia, we demonstrate that ventral hippocampal (vHipp) deep brain stimulation (DBS) can normalize aberrant dopamine neuron activity and behaviours associated with positive symptoms. In addition, we provide evidence that this approach may also be effective in restoring deficits in cognitive function, often left unaltered by conventional antipsychotic medications. Therefore, we have provided initial preclinical evidence demonstrating the feasibility of hippocampal DBS as a potential novel approach for the treatment of schizophrenia.

  3. Hippocampal GABA transporter distribution in patients with temporal lobe epilepsy and hippocampal sclerosis

    NARCIS (Netherlands)

    Schijns, O.; Karaca, U.; Andrade, P.; Nijs, L. de; Kusters, B.; Peeters, A.; Dings, J.; Pannek, H.; Ebner, A.; Rijkers, K.; Hoogland, G.

    2015-01-01

    PURPOSE: 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). METHODS: Hippocampal sections were immunohistochemically stained for GABA-transporter 1 and GABA-transpor

  4. Post-Materialism : A Cultural Factor Influencing Total Entrepreneurial Activity Across Nations

    OpenAIRE

    Uhlaner, Lorraine; Thurik, A. Roy

    2004-01-01

    The study of predictors of entrepreneurial activity at the country level has been dominated by economic influences. However, the relative stability of differences in entrepreneurial activity across countries suggests that other forces such as institutional and/or cultural factors are at play. The objective of this paper is to explore more specifically how post-materialism may help to explain differences in total entrepreneurial activity across countries. Total entrepreneurial activity is defi...

  5. Activated Sludge and Other Aerobic Suspended Culture Processes

    Directory of Open Access Journals (Sweden)

    Yung-Tse Hung

    2011-08-01

    Full Text Available A review of the literature published in 2008, 2009 and 2010 relating to activated sludge treatment of wastewater is presented. The review considers information on the topics of modeling and kinetics; process microbiology; nitrogen and phosphorus removal; treatment and effects of xenobiotics; oxygen transfer; and solids separation.

  6. Exploring Formative Assessment Using Cultural Historical Activity Theory

    Science.gov (United States)

    Asghar, Mandy

    2013-01-01

    Formative assessment is a pedagogic practice that has been the subject of much research and debate, as to how it can be used most effectively to deliver enhanced student learning in the higher education setting. Often described as a complex concept it embraces activities that range from facilitating students understanding of assessment standards,…

  7. Anthropological Approach and Activity Theory: Culture, Communities and Institutions

    Science.gov (United States)

    Lagrange, Jean-Baptiste

    2013-01-01

    The goal of this paper is to evaluate the contribution of the anthropological approach (AA) concurrently to Activity Theory (AT) in view of overarching questions about classroom use of technology for teaching and learning mathematics. I will do it first from a philosophical point of view, presenting the main notions of AA that have been used to…

  8. Involvement of ryanodine receptors in neurotrophin-induced hippocampal synaptic plasticity and spatial memory formation

    OpenAIRE

    Adasme, Tatiana; Haeger, Paola; Paula-Lima, Andrea C.; Espinoza, Italo; Casas-Alarcón, M. Mercedes; Carrasco, M. Angélica; Hidalgo, Cecilia

    2011-01-01

    Ryanodine receptors (RyR) amplify activity-dependent calcium influx via calcium-induced calcium release. Calcium signals trigger postsynaptic pathways in hippocampal neurons that underlie synaptic plasticity, learning, and memory. Recent evidence supports a role of the RyR2 and RyR3 isoforms in these processes. Along with calcium signals, brain-derived neurotrophic factor (BDNF) is a key signaling molecule for hippocampal synaptic plasticity and spatial memory. Upon binding to specific TrkB r...

  9. Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis?

    OpenAIRE

    Damien eBonhomme; Amandine Marie Minni; Serge eAlfos; Pascale eRoux; Emmanuel eRichard; Paul eHigueret; Marie-Pierre eMoisan; Véronique ePallet; Katia eTouyarot

    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 ...

  10. Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term, but not short-term, hippocampus-dependent memory.

    Science.gov (United States)

    Gould, Thomas J; Wilkinson, Derek S; Yildirim, Emre; Poole, Rachel L F; Leach, Prescott T; Simmons, Steven J

    2014-03-01

    Acute nicotine enhances hippocampus-dependent learning through nicotine binding to β2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but not 2 h post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PKA activity blocked the effect of acute nicotine on learning, and nicotine shifted the timing of learning-related PKA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA and ERK1/2 activity could contribute to the strength of memories.

  11. MILK KEFIR: COMPOSITION, MICROBIAL CULTURES, BIOLOGICAL ACTIVITIES AND RELATED PRODUCTS

    Directory of Open Access Journals (Sweden)

    Maria Rosa Prado

    2015-10-01

    Full Text Available In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance.

  12. Emotion at Work: A Contribution to Third-Generation Cultural-Historical Activity Theory

    Science.gov (United States)

    Roth, Wolff-Michael

    2007-01-01

    Second-generation cultural-historical activity theory, which drew its inspiration from Leont'ev's work, constituted an advance over Vygotsky's first-generation theory by explicitly articulating the dialectical relation between individual and collective. As part of an effort to develop third-generation-historical activity theory, I propose in this…

  13. Cultural-Historical Activity Theory and Domain Analysis: Metatheoretical Implications for Information Science

    Science.gov (United States)

    Wang, Lin

    2013-01-01

    Background: Cultural-historical activity theory is an important theory in modern psychology. In recent years, it has drawn more attention from related disciplines including information science. Argument: This paper argues that activity theory and domain analysis which uses the theory as one of its bases could bring about some important…

  14. Dialogue--Missing in Action Competence: A Cultural Historical Activity Theory Approach in a Botswana School

    Science.gov (United States)

    Silo, Nthalivi

    2013-01-01

    An in-depth case study on children's participation in environmental management activities in a primary school in Botswana was undertaken, drawing on cultural historical activity theory (CHAT) and the action competence model. This research revealed that due to a lack of dialogue between teachers and children, teachers tended to view children's…

  15. An Overview of Cultural Historical Activity Theory (CHAT) Use in Classroom Research 2000 to 2009

    Science.gov (United States)

    Nussbaumer, Doris

    2012-01-01

    Western educational researchers have eagerly accepted activity theory (AT) also known as cultural historical activity theory (CHAT) to collect and analyze data in rich description of complex situations. As this theory is applicable to a wide variety of disciplines, this review is limited to education and specifically to qualitative studies of…

  16. Understanding Preschool Emergent Science in a Cultural Historical Context through Activity Theory

    Science.gov (United States)

    Sundberg, Bodil; Areljung, Sofie; Due, Karin; Ekström, Kenneth; Ottander, Christina; Tellgren, Britt

    2016-01-01

    The aim of this study is to explore how cultural factors interact with preschool teachers' shaping of activities with science content, and also how Activity Theory (AT) as a theoretical framework can be useful for examining interrelations within preschool systems. Qualitative data was collected from three preschools in the form of guided group…

  17. Superoxide dismutase activity as a function of culture aging of B-16 mouse melanoma cells

    Directory of Open Access Journals (Sweden)

    JOVANA B. SIMIC-KRSTIC

    2004-12-01

    Full Text Available The C3 clone of B-16 mouse melanoma was cultured for 1, 6 and 9 days and analysed. The changes which are not directly linked to melanogenesis in the B-16 / C3 cultures during their maturation were characterized. Early (1 day, confluent (6 days and old (9 days cell cultures are distinguished by their leucine aminopeptidase (LAP and a-naphthyl acetate esterase (ANAE isoenzyme patterns. Both quantitative and qualitative changes in LAP and ANAE isoenzyme can be observed during culture maturation. There is an increase in the activity of the enzyme copper, zinc-containing superoxide-dismutase (CuZn SOD. The increaase in the CuZn SOD enzyme activity might be related to B-16/C3 cell melanogenesis and / or to differentiation.

  18. Cell culture density affects the proliferation activity of human adipose tissue stem cells.

    Science.gov (United States)

    Kim, Dae Seong; Lee, Myoung Woo; Ko, Young Jong; Chun, Yong Hoon; Kim, Hyung Joon; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2016-01-01

    In this study, we investigated the effect of cell density on the proliferation activity of human mesenchymal stem cells (MSCs) derived from adipose tissue (AT-MSCs) over time in culture. Passage #4 (P4) and #12 (P12) AT-MSCs from two donors were plated at a density of 200 (culture condition 1, CC1) or 5000 (culture condition 2, CC2) cells cm(-2) . After 7 days of incubation, P4 and P12 AT-MSCs cultured in CC1 were thin and spindle-shaped, whereas those cultured in CC2 had extensive cell-to-cell contacts and an expanded cell volume. In addition, P4 and P12 AT-MSCs in CC1 divided more than three times, while those in CC2 divided less than once on average. Flow cytometric analysis using 5(6)-carboxyfluorescein diacetate N-succinimidyl ester dye showed that the fluorescence intensity of AT-MSCs was lower in CC1 than in CC2. Furthermore, expression of proliferation-associated genes, such as CDC45L, CDC20A and KIF20A, in P4 AT-MSCs was higher in CC1 than in CC2, and this difference was also observed in P12 AT-MSCs. These data demonstrated that cell culture density affects the proliferation activity of MSCs, suggesting that it is feasible to design a strategy to prepare suitable MSCs using specific culture conditions.

  19. Angiotensin converting enzyme 2 (ACE2) activity in fetal calf serum: implications for cell culture research

    OpenAIRE

    Lubel, J. S.; Herath, C. B.; Velkoska, E.; Casley, D. J.; Burrell, L. M.; Angus, P. W.

    2008-01-01

    Cell culture experiments often employ the use of culture media that contain fetal calf serum (FCS). The angiotensin peptides angiotensin II and angiotensin 1–7 have opposing effects with angiotensin converting enzyme 2 (ACE2) being the enzyme predominantly responsible for generating angiotensin 1–7 from angiotensin II. The effect of FCS on angiotensin peptides has not previously been described. We have shown that FCS has ACE2 enzyme activity capable of degrading angiotensin II and generating ...

  20. Enhanced Antitumoral Activity of Extracts Derived from Cultured Udotea flabellum (Chlorophyta

    Directory of Open Access Journals (Sweden)

    Rosa Moo-Puc

    2011-01-01

    Full Text Available Very few studies have been performed to evaluate the effect of culture conditions on the production or activity of active metabolites in algae. Previous studies suggest that the synthesis of bioactive compounds is strongly influenced by irradiance level. To investigate whether the antiproliferative activity of Udotea flabellum extracts is modified after cultivation, this green alga was cultured under four photon flux densities (PFD for 30 days. After 10, 20, and 30 days, algae were extracted with dichloromethane: methanol and screened for antiproliferative activity against four human cancer cell lines (laryngeal—Hep-2, cervix—HeLa, cervix squamous—SiHa and nasopharynx—KB by SRB assay. Lipid and phenol content were evaluated by standardized methods on algae organic extracts. After 10 days of cultivation, organic U. flabellum extracts showed a significant increase in antiproliferative activity on Hela and SiHa cells when compared to noncultured algae extracts. Extracts obtained after 10 and 20 days of culture were active on KB and Hep-2 cells. Total phenol and polyunsaturated fatty acid content in organic extracts changed with cultivation time but not by irradiance treatment. Extracts from U. flabellum obtained after 10 and 20 days of culture have been selected for fractionation and isolation of active compounds.

  1. RELATIONSHIP OF THE PERSONAL PSYCHOLOGICAL CULTURE AND EFFICIENCY OF THE PEDAGOGICAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    Nadezhda Yuryevna Belova

    2015-02-01

    Full Text Available The paper presents empirical evidence of psychological relationship of culture and the success of teachers, which is important in the context of a new educational paradigm, one of the priorities of which is the formation of «human culture». Distinctive features of the psychologically cultural teacher – is to develop skills of self-regulation of personality states, activities and relationships with other people, a high level of adaptability and the ability to predict and evaluate the results of its activities, including professional. There has also been underlined the specificity of the identified interrelation among university, college and school teachers.Purpose. In the course of theoretical and experimental research to establish the success of the growth opportunities of teachers by improving their cultural potential.Methodology or the methodology of work. As an organizational method, method of transverse sections has been used. The study used well known standard techniques: self-constructed reports, as well as the method of peer review activities.Results. The obtained results of the pilot study indicate a strong relationship between the components of psychological culture and teaching activities, individual psychological characteristics and education, acting as a subjective potential of a teacher and leading to a success in his professional activities, and are largely determined by the development of psychological culture.Scope results. The results of the study will benefit in the development of training programs for university professors, college and school teachers in the context of the growth of their psychological culture, taking into account peculiarities of manifestation of this phenomenon.

  2. From network heterogeneities to familiarity detection and hippocampal memory management

    Science.gov (United States)

    Wang, Jane X.; Poe, Gina; Zochowski, Michal

    2008-10-01

    Hippocampal-neocortical interactions are key to the rapid formation of novel associative memories in the hippocampus and consolidation to long term storage sites in the neocortex. We investigated the role of network correlates during information processing in hippocampal-cortical networks. We found that changes in the intrinsic network dynamics due to the formation of structural network heterogeneities alone act as a dynamical and regulatory mechanism for stimulus novelty and familiarity detection, thereby controlling memory management in the context of memory consolidation. This network dynamic, coupled with an anatomically established feedback between the hippocampus and the neocortex, recovered heretofore unexplained properties of neural activity patterns during memory management tasks which we observed during sleep in multiunit recordings from behaving animals. Our simple dynamical mechanism shows an experimentally matched progressive shift of memory activation from the hippocampus to the neocortex and thus provides the means to achieve an autonomous off-line progression of memory consolidation.

  3. Enhancement of neuromuscular activity by natural specimens and cultured mycelia of Cordyceps Sinensis in mice

    Directory of Open Access Journals (Sweden)

    K P Singh

    2014-01-01

    Full Text Available The present study was aimed to evaluate the effect of natural specimen and laboratory cultured mycelia of Cordyceps sinensis on neuromuscular activity in mice. The powder of natural specimen and laboratory cultured Cordyceps sinensis was orally administered at the dose rate of 100, 300 and 500 mg/kg for 30 days. Natural specimen and in vitro propagated Cordyceps sinensis showed significant (P<0.05 enhancement in neuromuscular endurance and antidepressant activity at 300 and 500 mg/kg as compared to the control group. However, the fungus did not proved to be as effective as fluoxetine in exhibiting antidepressant action. Muscular endurance was determined on a Rota rod apparatus while antidepressant (mood elevating activity was measured on a photoactometer in Swiss albino mice. The effects produced by both natural specimens and laboratory cultured Cordyceps sinensis were comparable and showed almost equal potency.

  4. Histaminergic system in co-cultures of hippocampus and posterior hypothalamus: a morphological and electrophysiological study in the rat.

    Science.gov (United States)

    Diewald, L; Heimrich, B; Büsselberg, D; Watanabe, T; Haas, H L

    1997-11-01

    Neurons of the tuberomammillary nucleus in the posterior hypothalamus diffusely project to most parts of the central nervous system, where their main transmitter, histamine, modulates the excitability of the target neurons. The development of a histaminergic hypothalamo-hippocampal pathway and its function were studied in organotypic co-cultures. Immunocytochemistry for histidine decarboxylase, the specific synthesizing enzyme, stained clusters of neurons in the hypothalamic tuberomammillary area. Immunolabelled varicose processes innervated the co-cultured hippocampus and established a few synaptic contacts on dendrites. Cultured tuberomammillary neurons displayed their typical membrane properties and were spontaneously active. In hippocampal pyramidal cells of the CA3 region the long-lasting afterhyperpolarization was reduced by histamine or impromidine and increased by the H2 antagonist cimetidine, but not by the H1 antagonist mepyramine. The membrane potential was depolarized in presence of an H2 agonist and hyperpolarized by an H2 antagonist. In single hippocampal cultures histamine antagonists did not affect afterhyperpolarization and membrane potential. Histaminergic neurons retain their main morphological and physiological characteristics in slice cultures and establish a functional connection with co-cultured target cells.

  5. Absence of telomerase activity and telomerase catalytic subunit mRNA in melanocyte cultures

    OpenAIRE

    Dhaene, K.; Vancoillie, G; Lambert, J.; Naeyaert, J M; Van Marck, E

    2000-01-01

    The classic model of activation of telomerase, for which activity has been found in most cancers including cutaneous malignant melanoma (CMM), dictates that enzyme activity is generated by pathological reactivation of telomerase in telomerase-negative somatic cells. However, recent data demonstrated physiological up-regulation in some normal cell types when established as proliferating cultures, indicating that, in some cancer types, telomerase is expressed by the process of up-regulation in ...

  6. Inhibition on Telomerase Activity and Cytotoxic Effects by Cisplatin in Cultured Human Choroidal Melanoma Cells

    Institute of Scientific and Technical Information of China (English)

    Hao Cheng; Zhongyao Wu; Jianliang Zheng; Guilan Lu; Jianhua Yan; Min Liu; Danping Huang; Jianxian Lin

    2003-01-01

    Purpose: To study the changes of telomerase activity and cytotoxic effects by Cisplatin;cis-dichlorodiamine platinum (CDDP) in cultured human choroidal melanoma.Material and Methods: The primary cultured human choroidal melanoma cells werecultured in the presence and absence of CDDP with different concentration and timerespectively. The toxic effects were evaluated by MTT and the level of telormarse wasdetected by PCR-ELISA assay. And the relationship between telomerase activity andcytotoxic effects were analyzed by a correlation analysis.Results: Following the increase of the concentration and the time of CDDP, graduallyrepressed telomerase activity was detected in cultured cells. Meanwhile, the restrain rateof the cells increased. The telomerase activity at 24h and 1μg/ml was repressedsignificantly compared with the control cells. However, the appearance of cell deathlagged behind the decreasing of telomerase.Conclusions: CDDP is an effective telomerase inhibitor in cultured choroidal melanomacells of human eyes, which presents concentration and time dependency and can causethe death of cultured cells.

  7. Epigenetics, estradiol, and hippocampal memory consolidation

    OpenAIRE

    Frick, Karyn M.

    2013-01-01

    Epigenetic alterations of histone proteins and DNA are essential for hippocampal synaptic plasticity and cognitive function, and contribute to the etiology of psychiatric disorders and neurodegenerative diseases. Hippocampal memory formation depends on histone alterations and DNA methylation, and increasing evidence suggests that regulation of these epigenetic processes by modulatory factors such as environmental enrichment, stress, and hormones substantially influences memory function. Recen...

  8. Dependence of NMDA/GSK-3β Mediated Metaplasticity on TRPM2 Channels at Hippocampal CA3-CA1 Synapses

    Directory of Open Access Journals (Sweden)

    Xie Yu-Feng

    2011-12-01

    Full Text Available Abstract Transient receptor potential melastatin 2 (TRPM2 is a calcium permeable non-selective cation channel that functions as a sensor of cellular redox status. Highly expressed within the CNS, we have previously demonstrated the functional expression of these channels in CA1 pyramidal neurons of the hippocampus. Although implicated in oxidative stress-induced neuronal cell death, and potentially in neurodegenerative disease, the physiological role of TRPM2 in the central nervous system is unknown. Interestingly, we have shown that the activation of these channels may be sensitized by co-incident NMDA receptor activation, suggesting a potential contribution of TRPM2 to synaptic transmission. Using hippocampal cultures and slices from TRPM2 null mice we demonstrate that the loss of these channels selectively impairs NMDAR-dependent long-term depression (LTD while sparing long-term potentiation. Impaired LTD resulted from an inhibition of GSK-3β, through increased phosphorylation, and a reduction in the expression of PSD95 and AMPARs. Notably, LTD could be rescued in TRPM2 null mice by recruitment of GSK-3β signaling following dopamine D2 receptor stimulation. We propose that TRPM2 channels play a key role in hippocampal synaptic plasticity.

  9. RXRα, PXR and CAR xenobiotic receptors mediate the apoptotic and neurotoxic actions of nonylphenol in mouse hippocampal cells.

    Science.gov (United States)

    Litwa, E; Rzemieniec, J; Wnuk, A; Lason, W; Krzeptowski, W; Kajta, M

    2016-02-01

    In the present study, we investigated the role of the retinoid X receptor (RXR), the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), in the apoptotic and toxic effects of nonylphenol in mouse primary neuronal cell cultures. Our study demonstrated that nonylphenol activated caspase-3 and induced lactate dehydrogenase (LDH) release in hippocampal cells, which was accompanied by an increase in the mRNA expression and protein levels of RXRα, PXR and CAR. Nonylphenol stimulated Rxra, Pxr, and Car mRNA expression. These effects were followed by increase in the protein levels of particular receptors. Immunofluorescence labeling revealed the cellular distribution of RXRα, PXR and CAR in hippocampal neurons in response to nonylphenol, shortening of neurites and cytoplasmic shrinking, as indicated by MAP2 staining. It also showed NP-induced translocation of receptor-specific immunofluorescence from cytoplasm to the nucleus. The use of specific siRNAs demonstrated that Rxra-, Pxr-, and Car-siRNA-transfected cells were less vulnerable to nonylphenol-induced activation of caspase-3 and LDH, thus confirming the key involvement of RXRα/PXR/CAR signaling pathways in the apoptotic and neurotoxic actions of nonylphenol. These new data give prospects for the targeting xenobiotic nuclear receptors to protect the developing nervous system against endocrine disrupting chemicals. PMID:26643981

  10. Nonlinear modeling of neural population dynamics for hippocampal prostheses

    OpenAIRE

    Song, Dong; Chan, Rosa H.M.; Vasilis Z Marmarelis; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.

    2009-01-01

    Developing a neural prosthesis for the damaged hippocampus requires restoring the transformation of population neural activities performed by the hippocampal circuitry. To bypass a damaged region, output spike trains need to be predicted from the input spike trains and then reinstated through stimulation. We formulate a multiple-input, multiple-output (MIMO) nonlinear dynamic model for the input–output transformation of spike trains. In this approach, a MIMO model comprises a series of physio...

  11. Hippocampal sleep features: relations to human memory function

    OpenAIRE

    Michele eFerrara; Fabio eMoroni; Luigi eDe Gennaro; Lino eNobili

    2012-01-01

    The recent spread of intracranial EEG recordings techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The stu...

  12. Hippocampal Sleep Features: Relations to Human Memory Function

    OpenAIRE

    Ferrara, Michele; Moroni, Fabio; De Gennaro, Luigi; Nobili, Lino

    2012-01-01

    The recent spread of intracranial electroencephalographic (EEG) recording techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially g...

  13. Repeating Spatial-Temporal Motifs of CA3 Activity Dependent on Engineered Inputs from Dentate Gyrus Neurons in Live Hippocampal Networks.

    Science.gov (United States)

    Bhattacharya, Aparajita; Desai, Harsh; DeMarse, Thomas B; Wheeler, Bruce C; Brewer, Gregory J

    2016-01-01

    Anatomical and behavioral studies, and in vivo and slice electrophysiology of the hippocampus suggest specific functions of the dentate gyrus (DG) and the CA3 subregions, but the underlying activity dynamics and repeatability of information processing remains poorly understood. To approach this problem, we engineered separate living networks of the DG and CA3 neurons that develop connections through 51 tunnels for axonal communication. Growing these networks on top of an electrode array enabled us to determine whether the subregion dynamics were separable and repeatable. We found spontaneous development of polarized propagation of 80% of the activity in the native direction from DG to CA3 and different spike and burst dynamics for these subregions. Spatial-temporal differences emerged when the relationships of target CA3 activity were categorized with to the number and timing of inputs from the apposing network. Compared to times of CA3 activity when there was no recorded tunnel input, DG input led to CA3 activity bursts that were 7× more frequent, increased in amplitude and extended in temporal envelope. Logistic regression indicated that a high number of tunnel inputs predict CA3 activity with 90% sensitivity and 70% specificity. Compared to no tunnel input, patterns of >80% tunnel inputs from DG specified different patterns of first-to-fire neurons in the CA3 target well. Clustering dendrograms revealed repeating motifs of three or more patterns at up to 17 sites in CA3 that were importantly associated with specific spatial-temporal patterns of tunnel activity. The number of these motifs recorded in 3 min was significantly higher than shuffled spike activity and not seen above chance in control networks in which CA3 was apposed to CA3 or DG to DG. Together, these results demonstrate spontaneous input-dependent repeatable coding of distributed activity in CA3 networks driven by engineered inputs from DG networks. These functional configurations at measured times

  14. Idaho National Laboratory Cultural Resource Management Office FY 2011 Activity Report

    Energy Technology Data Exchange (ETDEWEB)

    Julie Braun Williams; Brenda R. Pace; Hollie K. Gilbert; Christina L. Olson

    2012-09-01

    The Idaho National Laboratory (INL) Site is home to vast numbers and a wide variety of important cultural resources representing at least a 13,500 year span of human land use in the region. As a federal agency, the Department of Energy, Idaho Operations Office (DOE-ID) has legal responsibility for the management and protection of the resources and has contracted these responsibilities to Battelle Energy Alliance (BEA). The BEA professional staff is committed to maintaining a cultural resource management program that accepts the challenge of preserving INL cultural resources in a manner reflecting their importance in local, regional, and national history. This report is intended as a stand-alone document that summarizes activities performed by the INL Cultural Resource Management Office (CRMO) staff during fiscal year 2011. This work is diverse, far-reaching and though generally confined to INL cultural resource compliance, also includes a myriad of professional and voluntary community activities. This document is intended to be informative to both internal and external stakeholders, serve as a planning tool for future INL cultural resource management work, and meet an agreed upon legal requirement.

  15. Idaho National Laboratory Cultural Resource Management Office FY 2010 Activity Report

    Energy Technology Data Exchange (ETDEWEB)

    Hollie K. Gilbert; Clayton F. Marler; Christina L. Olson; Brenda R. Pace; Julie Braun Williams

    2011-09-01

    The Idaho National Laboratory (INL) Site is home to vast numbers and a wide variety of important cultural resources representing at least a 13,500 year span of human land use in the region. As a federal agency, the Department of Energy, Idaho Operations Office (DOE-ID) has legal responsibility for the management and protection of the resources and has contracted these responsibilities to Battelle Energy Alliance (BEA). The BEA professional staff is committed to maintaining a cultural resource management program that accepts the challenge of preserving INL cultural resources in a manner reflecting their importance in local, regional, and national history. This report summarizes activities performed by the INL Cultural Resource Management Office (CRMO) staff during fiscal year 2010. This work is diverse, far-reaching and though generally confined to INL cultural resource compliance, also includes a myriad of professional and voluntary community activities. This document is intended to be informative to both internal and external stakeholders and to serve as a planning tool for future INL cultural resource management work.

  16. Study of Ganoderma lucidum spores on pentylenetetrazol activation of hippocampal neurons bax expression%灵芝孢子粉对戊四氮活化海马神经细胞bax表达的研究

    Institute of Scientific and Technical Information of China (English)

    张金波; 王淑秋; 张淑红; 金岳雷; 朱金玲; 刘爽

    2012-01-01

    目的 本实验研究灵芝孢子粉对戊四氮活化大鼠海马神经细胞bax表达变化的影响,进一步探讨灵芝孢子粉的作用机制和癫痫与海马神经细胞凋亡调控基因之间的关系.方法 通过制备癫痫模型和RT-PCR检测正常对照组、癫痫模型组和灵芝孢子粉用药组bax的表达.结果 癫痫模型组和灵芝孢子粉用药组bax的表达较正常对照组(0.17±0.04)均升高;其中癫痫模型组(0.66±0.09)bax的表达水平与对照组(0.17±0.04)比较明显升高(P<0.01),灵芝孢子粉用药组(0.47±0.1)bax的表达水平与癫痫模型组比较明显降低(P<0.01),差异有统计学意义.结论 本研究结果证实,在PTZ点燃癫痫后,模型组和治疗组促凋亡基因bax表达较正常对照组显著升高,表明bax基因在细胞凋亡的调控过程中起到促进作用,而给予灵芝孢子粉治疗后,bax的表达与模型组比较显著降低,提示灵芝孢子粉有效成份能充分作用于脑组织,可以调控bax的表达,借以发挥抗凋亡的神经保护作用.%Objective; This study is Ganoderma lucidum spores on pentylenetetrazol activation of rat hippocampal neurons bax expression changes to further explore the relationship between the action mechanism of the Ganoderma lucidum spores and epilepsy with apoptosis regulatory genes of hippocampal neural. Methods; Through the preparation of the epileptic model and RT — PCR to detect of bax expression in the normal control group, epilepsy model group and Ganoderma spore powder medication group. Results;/ Bax expression in epilepsy model group and Ganoderma lucidum spores medication group were higher than in the normal control group (0. 17 ± 0. 04) ; including bax expression level in epilepsy model group (0. 66 ± 0. 09) was significantly higher than in the control group (0. 17 ± 0.04) (P<0. 01) , bax expression level in Ganoderma spore powder medication group (0.47 ± 0. 1 ) were significantly lower than in epilepsy model group

  17. Effect of Lactococcin BZ and Enterocin KP on the Activity of Yoghurt Cultures

    Directory of Open Access Journals (Sweden)

    Nilgün Öncül

    2015-02-01

    Full Text Available In this study, the effects of lactococcin BZ from Lactococcus lactis ssp. lactis BZ and enterocin KP from Enterococcus faecalis KP (1600 AU/mL on the activities of three different yoghurt cultures (Y1 and Y2: CHR Hansen, Denmark; Y3: Sacco, Italy were investigated. Lactic acid bacteria counts and pH values of the samples were determined during the incubation period (at 42°C for 24 h. It was found that lactococcin BZ had bactericidal effect against only one yoghurt culture whereas enterocin KP was effective against two yoghurt cultures. When lactococcin BZ and enterosin KP were used in combination (1:1, they showed bactericidal effect against two yoghurt cultures.

  18. T Lymphocyte Activation Threshold and Membrane Reorganization Perturbations in Unique Culture Model

    Science.gov (United States)

    Adams, C. L.; Sams, C. F.

    2000-01-01

    Quantitative activation thresholds and cellular membrane reorganization are mechanisms by which resting T cells modulate their response to activating stimuli. Here we demonstrate perturbations of these cellular processes in a unique culture system that non-invasively inhibits T lymphocyte activation. During clinorotation, the T cell activation threshold is increased 5-fold. This increased threshold involves a mechanism independent of TCR triggering. Recruitment of lipid rafts to the activation site is impaired during clinorotation but does occur with increased stimulation. This study describes a situation in which an individual cell senses a change in its physical environment and alters its cell biological behavior.

  19. Environmental, policy, and cultural factors related to physical activity in African American women.

    Science.gov (United States)

    Richter, Donna L; Wilcox, Sara; Greaney, Mary L; Henderson, Karla A; Ainsworth, Barbara E

    2002-01-01

    Six focus groups were conducted in South Carolina with African American women (n = 42) aged 19-51 years to identify factors that influence physical activity. Transcripts were analyzed using NUD*IST. Cultural influences were seen as more important in determining the type of physical activity than its level. Barriers to and enablers of physical activity were identified in the social and physical environments, as were policy issues affecting physical activity in the community and at the work site. Potential community and work site interventions were suggested. Child care and monetary costs were frequently cited as barriers to physical activity. PMID:12487143

  20. Dipeptide Piracetam Analogue Noopept Improves Viability of Hippocampal HT-22 Neurons in the Glutamate Toxicity Model.

    Science.gov (United States)

    Antipova, T A; Nikolaev, S V; Ostrovskaya, P U; Gudasheva, T A; Seredenin, S B

    2016-05-01

    Effect of noopept (N-phenylacetyl-prolylglycine ethyl ester) on viability of neurons exposed to neurotoxic action of glutamic acid (5 mM) was studied in vitro in immortalized mouse hippocampal HT-22 neurons. Noopept added to the medium before or after glutamic acid improved neuronal survival in a concentration range of 10-11-10-5 M. Comparison of the effective noopept concentrations determined in previous studies on cultured cortical and cerebellar neurons showed that hippocampal neurons are more sensitive to the protective effect of noopept. PMID:27265136

  1. Initiation of sleep-dependent cortical-hippocampal correlations at wakefulness-sleep transition.

    Science.gov (United States)

    Haggerty, Daniel C; Ji, Daoyun

    2014-10-01

    Sleep is involved in memory consolidation. Current theories propose that sleep-dependent memory consolidation requires active communication between the hippocampus and neocortex. Indeed, it is known that neuronal activities in the hippocampus and various neocortical areas are correlated during slow-wave sleep. However, transitioning from wakefulness to slow-wave sleep is a gradual process. How the hippocampal-cortical correlation is established during the wakefulness-sleep transition is unknown. By examining local field potentials and multiunit activities in the rat hippocampus and visual cortex, we show that the wakefulness-sleep transition is characterized by sharp-wave ripple events in the hippocampus and high-voltage spike-wave events in the cortex, both of which are accompanied by highly synchronized multiunit activities in the corresponding area. Hippocampal ripple events occur earlier than the cortical high-voltage spike-wave events, and hippocampal ripple incidence is attenuated by the onset of cortical high-voltage spike waves. This attenuation leads to a temporary weak correlation in the hippocampal-cortical multiunit activities, which eventually evolves to a strong correlation as the brain enters slow-wave sleep. The results suggest that the hippocampal-cortical correlation is established through a concerted, two-step state change that first synchronizes the neuronal firing within each brain area and then couples the synchronized activities between the two regions.

  2. Synapse-specific inhibitory control of hippocampal feedback inhibitory circuit

    Directory of Open Access Journals (Sweden)

    Simon eChamberland

    2010-10-01

    Full Text Available Local circuit and long-range GABAergic projections provide powerful inhibitory control over the operation of hippocampal inhibitory circuits, yet little is known about the input- and target-specific organization of interacting inhibitory networks in relation to their specific functions. Using a combination of two-photon laser scanning photostimulation and whole-cell patch clamp recordings in mice hippocampal slices, we examined the properties of transmission at GABAergic synapses formed onto hippocampal CA1 stratum oriens – lacunosum moleculare (O–LM interneurons by two major inhibitory inputs: local projection originating from stratum radiatum interneurons and septohippocampal GABAergic terminals. Optical mapping of local inhibitory inputs to O–LM interneurons revealed that vasoactive intestinal polypeptide- and calretinine-positive neurons, with anatomical properties typical of type III interneuron-specific interneurons, provided the major local source of inhibition to O–LM cells. Inhibitory postsynaptic currents evoked by minimal stimulation of this input exhibited small amplitude and significant paired-pulse and multiple-pulse depression during repetitive activity. Moreover, these synapses failed to show any form of long-term synaptic plasticity. In contrast, synapses formed by septohippocampal projection produced higher amplitude and persistent inhibition and exhibited long-term potentiation induced by theta-like activity. These results indicate the input and target-specific segregation in inhibitory control, exerted by two types of GABAergic projections and responsible for distinct dynamics of inhibition in O–LM interneurons. The two inputs are therefore likely to support the differential activity- and brain state-dependent recruitment of hippocampal feedback inhibitory circuits in vivo, crucial for dendritic disinhibition and computations in CA1 pyramidal cells.

  3. In vitro culture of functionally active buffalo hepatocytes isolated by using a simplified manual perfusion method.

    Directory of Open Access Journals (Sweden)

    Santanu Panda

    Full Text Available In farm animals, there is no suitable cell line available to understand liver-specific functions. This has limited our understanding of liver function and metabolism in farm animals. Culturing and maintenance of functionally active hepatocytes is difficult, since they survive no more than few days. Establishing primary culture of hepatocytes can help in studying cellular metabolism, drug toxicity, hepatocyte specific gene function and regulation. Here we provide a simple in vitro method for isolation and short-term culture of functionally active buffalo hepatocytes.Buffalo hepatocytes were isolated from caudate lobes by using manual enzymatic perfusion and mechanical disruption of liver tissue. Hepatocyte yield was (5.3 ± 0.66×107 cells per gram of liver tissue with a viability of 82.3 ± 3.5%. Freshly isolated hepatocytes were spherical with well contrasted border. After 24 hours of seeding onto fibroblast feeder layer and different extracellular matrices like dry collagen, matrigel and sandwich collagen coated plates, hepatocytes formed confluent monolayer with frequent clusters. Cultured hepatocytes exhibited typical cuboidal and polygonal shape with restored cellular polarity. Cells expressed hepatocyte-specific marker genes or proteins like albumin, hepatocyte nuclear factor 4α, glucose-6-phosphatase, tyrosine aminotransferase, cytochromes, cytokeratin and α1-antitrypsin. Hepatocytes could be immunostained with anti-cytokeratins, anti-albumin and anti α1-antitrypsin antibodies. Abundant lipid droplets were detected in the cytosol of hepatocytes using oil red stain. In vitro cultured hepatocytes could be grown for five days and maintained for up to nine days on buffalo skin fibroblast feeder layer. Cultured hepatocytes were viable for functional studies.We developed a convenient and cost effective technique for hepatocytes isolation for short-term culture that exhibited morphological and functional characteristics of active hepatocytes

  4. The importance of culturally meaningful activity for health benefits among older Korean immigrant living in the United States

    Directory of Open Access Journals (Sweden)

    Junhyoung Kim

    2015-06-01

    Full Text Available Research indicates that participation in culturally meaningful activity is beneficial for immigrants’ health and well-being, yet older Korean immigrants struggle with accepting new cultural perspectives, which can negatively affect their health and well-being. Using in-depth interviews, this study was designed to capture the value of culturally meaningful activities for health among older Korean immigrants. Three themes were identified: (a improved psychological well-being, (b enhanced positive emotions and feelings, and (c social connections developed with others. The findings suggest that by engaging in various culturally meaningful activities, older Korean immigrants gain a sense of social, cultural, and psychological significance in life. This study also provided evidence that older Korean immigrants maintain and develop their cultural identity through culturally meaningful activities.

  5. Lipoxygenase activity and sanguinarine production in cell suspension cultures of California poppy (Eschscholtzia californica CHAM.).

    Science.gov (United States)

    Kollárová, R; Oblozinský, M; Kováciková, V; Holková, I; Balazová, A; Pekárová, M; Hoffman, P; Bezáková, L

    2014-08-01

    In this study we investigated the influence of biotic elicitor (phytopathogenic fungus Botrytis cinerea) and abiotic elicitors (methyljasmonate [MJ] and salicylic acid [SA]) on lipoxygenase (LOX) activity and sanguinarine production in cell suspension cultures of California poppy (Eschscholtzia californica CHAM.). We have observed different time effects of elicitors (10, 24, 48 and 72 h) on LOX activity and production of sanguinarine in in vitro cultures. All elicitors used in the experiments evidently increased the LOX activity and sanguinarine production in contrast to control samples. The highest LOX activities were determined in samples elicitated by MJ after 48 h and 72 h and the lowest LOX activities (in contrast to control samples) were detected after biotic elicitation by Botrytis cinerea. These activities showed about 50% lower level against the activities after MJ elicitation. The maximal amount of sanguinarine was observed after 48 h in MJ treated cultures (429.91 mg/g DCW) in comparision with control samples. Although all elicitors affect the sanguinarine production, effect of SA and biotic elicitor on sanguinarine accumulation in in vitrocultures was not so significant than after MJ elicitation. PMID:25158577

  6. Hippocampal ensemble dynamics timestamp events in long-term memory.

    Science.gov (United States)

    Rubin, Alon; Geva, Nitzan; Sheintuch, Liron; Ziv, Yaniv

    2015-01-01

    The capacity to remember temporal relationships between different events is essential to episodic memory, but little is currently known about its underlying mechanisms. We performed time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environments. Longitudinal analysis exposed ongoing environment-independent evolution of episodic representations, despite stable place field locations and constant remapping between the two environments. These dynamics time-stamped experienced events via neuronal ensembles that had cellular composition and activity patterns unique to specific points in time. Temporally close episodes shared a common timestamp regardless of the spatial context in which they occurred. Temporally remote episodes had distinct timestamps, even if they occurred within the same spatial context. Our results suggest that days-scale hippocampal ensemble dynamics could support the formation of a mental timeline in which experienced events could be mnemonically associated or dissociated based on their temporal distance. PMID:26682652

  7. Damage of hippocampal neurons in rats with chronic alcoholism

    Institute of Scientific and Technical Information of China (English)

    Ailin Du; Hongbo Jiang; Lei Xu; Na An; Hui Liu; Yinsheng Li; Ruiling Zhang

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deifcits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6%alcohol for 42 days. Endog-enous hydrogen sulifde content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were signiifcantly increased, while F-actin expression was decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a fuzzy nuclear mem-brane, mitochondrial edema, and ruptured mitochondrial crista. These findings suggest that chronic alcoholism can cause learning and memory decline in rats, which may be associated with the hydrogen sulfide/cystathionine-beta-synthase system, mitochondrial damage and reduced expression of F-actin.

  8. Hippocampal place cells construct reward related sequences through unexplored space.

    Science.gov (United States)

    Ólafsdóttir, H Freyja; Barry, Caswell; Saleem, Aman B; Hassabis, Demis; Spiers, Hugo J

    2015-06-26

    Dominant theories of hippocampal function propose that place cell representations are formed during an animal's first encounter with a novel environment and are subsequently replayed during off-line states to support consolidation and future behaviour. Here we report that viewing the delivery of food to an unvisited portion of an environment leads to off-line pre-activation of place cells sequences corresponding to that space. Such 'preplay' was not observed for an unrewarded but otherwise similar portion of the environment. These results suggest that a hippocampal representation of a visible, yet unexplored environment can be formed if the environment is of motivational relevance to the animal. We hypothesise such goal-biased preplay may support preparation for future experiences in novel environments.

  9. Implementing and measuring safety goals and safety culture. 4. Utility's Activities for Better Safety Culture After the JCO Accident

    International Nuclear Information System (INIS)

    The criticality accident at the JCO plant prompted the Government to enact a law for nuclear emergency preparedness. The nuclear industry established NSnet to facilitate opportunities for peer review among its members. This paper describes the activities by NSnet and TEPCO's Kashiwazaki-Kariwa nuclear power station (NPS) for a better safety culture. Created as a voluntary organization by the nuclear industry in 1999, NSnet has 35 members and is assisted by CRIEPI and NUPEC for its activities relevant to human factors. Given the fact that nuclear facility operators not belonging to WANO had no institutional system available for exchange of experiences and good practices for better safety among themselves, NSnet's activities focus on peer review by member organizations and onsite seminars. Starting April 2000 with visits to three fuel fabricators, NSnet intends to have 23 peer-review visits in 2 yr (Ref. 1). The six-member review team stays on-site for 4 days, during which time they review-using guidelines available from WANO and IAEA-OSART-six areas: organization/management, emergency preparedness, education/training, operation/ maintenance, protection against occupational radiation exposure, and prevention of accidents. A series of on-site seminars is held at members' nuclear facilities, to which NSnet dispatches experts for lectures. NSnet plans to hold such seminars twice per month. Other activities include information-sharing through a newsletter, a Web site (www. nsnet.gr.jp), and others. Although considerable differences exist in the design and the practices in operation/maintenance between power reactors and JCO, utilities can extract lessons from the accident that will be worth consideration for their own facilities in the areas of safety culture, education and training, and interface between design and operation. This thinking prompted the Nuclear Safety Promotion Center at Kashiwazaki-Kariwa NPS, to which the author belonged at that time, to launch the

  10. Framing Cross-Cultural Ethical Practice in Adapt[ive] Physical Activity

    Science.gov (United States)

    Goodwin, Donna; Howe, P. David

    2016-01-01

    Academics and practitioners are often at a loss when it comes to understanding the ethical socio-political and cultural contexts that invade the world of adapted physical activity. Ethical practice is situated in the local and the specific. In this article we highlight the reality that both academics and practitioners need to be ever mindful that…

  11. Proteolytic Activation of the Porcine Epidemic Diarrhea Coronavirus Spike Fusion Protein by Trypsin in Cell Culture.

    NARCIS (Netherlands)

    Wicht, Oliver; Li, Wentao; Willems, Lione; Meuleman, Tom J; Wubbolts, Richard W; van Kuppeveld, Frank J M; Rottier, Peter J M; Bosch, Berend Jan

    2014-01-01

    Isolation of porcine epidemic diarrhea coronavirus (PEDV) from clinical material in cell culture requires supplementation of trypsin. This may relate to the confinement of PEDV natural infection to the protease-rich small intestine of pigs. Our study focused on the role of protease activity on infec

  12. Wave shape classification of spontaneous neuronal activity in cortical cultures on micro-electrode arrays

    OpenAIRE

    Staveren, van, R.; Buitenweg, J.R.; Heida, T.; Rutten, W.L.C.

    2002-01-01

    Dissociated embryonal or postnatal rat cortical cells were cultured onto multi electrode arrays (MEA's) with 61 electrode sites. They developed into networks and became spontaneously active after about one week in vitro. About 180,000 recorded action potential waveforms were sorted using several spike features and classified with a Mahalanobis distance sorting procedure. They were classified into six basic wave shapes.

  13. Wave shape classification of spontaneous neuronal activity in cortical cultures on micro-electrode arrays

    NARCIS (Netherlands)

    Staveren, van G.W.; Buitenweg, J.R.; Heida, T.; Rutten, W.L.C.

    2002-01-01

    Dissociated embryonal or postnatal rat cortical cells were cultured onto multi electrode arrays (MEA's) with 61 electrode sites. They developed into networks and became spontaneously active after about one week in vitro. About 180,000 recorded action potential waveforms were sorted using several spi

  14. Accion Cultural Popular. [Summary Working Documents on ACPO's Conceptual Framework and Activities].

    Science.gov (United States)

    Bernal, Hernando; And Others

    Three papers are included in this document designed to provide English language information about characteristics and activities of Accion Cultural Popular (ACPO) a private, nonprofit organization concerned with improving the quality of life of rural populations and promoting rural development through mass media education programs. "Pioneer…

  15. Understanding and Dismantling Barriers for Partnerships for Inclusive Education: A Cultural Historical Activity Theory Perspective

    Science.gov (United States)

    Waitoller, Federico R.; Kozleski, Elizabeth B.

    2013-01-01

    Increasingly, universities and school districts share responsibility for teacher and student learning. Sharing responsibility demands that both institutions work to develop closer relationships through ongoing engagement, dialogue and negotiation. Drawing from Cultural Historical Activity Theory (CHAT), we examined one school/university…

  16. Cultural-Historical Activity Theory: Vygotsky's Forgotten and Suppressed Legacy and Its Implication for Mathematics Education

    Science.gov (United States)

    Roth, Wolff-Michael

    2012-01-01

    Cultural-historical activity theory--with historical roots in dialectical materialism and the social psychology to which it has given rise--has experienced exponential growth in its acceptance by scholars interested in understanding knowing and learning writ large. In education, this theory has constituted something like a well kept secret that is…

  17. Methodologies in Cultural-Historical Activity Theory: The Example of School-Based Development

    Science.gov (United States)

    Postholm, May Britt

    2015-01-01

    Background and purpose: Relatively little research has been conducted on methodology within Cultural-Historical Activity Theory (CHAT). CHAT is mainly used as a framework for developmental processes. The purpose of this article is to discuss both focuses for research and research questions within CHAT and to outline methodologies that can be used…

  18. Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    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.

  19. Post-Materialism as a Cultural Factor Influencing Entrepreneurial Activity across Nations

    OpenAIRE

    Uhlaner, Lorraine; Thurik, Roy; Hutjes, J.

    2002-01-01

    textabstractThe study of the determinants of entrepreneurship at the country level has been dominated by economic influences. The relative stability of differences in levels of entrepreneurship across coun-tries suggests that other forces such as certain institutional and/or cultural factors are at play. The objective of this paper is to explore how post-materialism explains differences in entrepreneurial activity across countries. Entrepreneurial activity is defined as the percent of a count...

  20. HIPPOCAMPAL SPINE-ASSOCIATED Rap-SPECIFIC GTPase-ACTIVATING PROTEIN INDUCES ENHANCEMENT OF LEARNING AND MEMORY IN POSTNATALLY HYPOXIA-EXPOSED MICE

    OpenAIRE

    Lu, X.-J.; Chen, X. -Q; Weng, J.; Zhang, H.-Y.; PAK, D. T.; LUO, J.-H.; DU, J.-Z.

    2009-01-01

    Spine-associated Rap-specific GTPase-activating protein (SPAR) is a postsynaptic protein that forms a complex with postsynaptic density (PSD)-95 and N-methyl-D-aspartate receptors (NMDARs), and morphologically regulates dendritic spines. Mild intermittent hypoxia (IH, 16.0% O2, 4 h/day for 4 weeks) is known to markedly enhance spatial learning and memory in postnatal developing mice. Here, we report that this effect is correlated with persistent increases in SPAR expression as well as long-te...

  1. Interfering with post-learning hippocampal activity does not affect long-term consolidation of a context fear memory outside the hippocampus.

    Science.gov (United States)

    Gulbrandsen, Tine L; Sparks, Fraser T; Sutherland, Robert J

    2013-03-01

    There are still uncertainties about the role of the hippocampus (HPC) in memory consolidation. One theory, systems consolidation, states that the HPC is required for the initial storage of certain memories that subsequently become established in non-HPC networks through a lengthy process, involving an interaction with the HPC. A similar process may underlie the ability of multiple, distributed learning episodes of contextual fear conditioning to create a HPC-independent context fear memory, in a memory task that does not undergo systems consolidation with the mere passage of time [5]. The current study examined whether post-learning HPC activity is necessary to establish these HPC-independent context memories through distributed learning episodes. Rats received either three or six context conditioning sessions over the course of three days. The HPC-dependence of context memories was assessed using multisite, temporary inactivation of the HPC using ropivacaine during retention testing. We established that six conditioning sessions, but not three, created a memory that could be retrieved while the HPC was inactive. To directly test our hypothesis, HPC was inactivated after half of the six context-shock pairings in an independent group of rats. The rats were then tested for retention of context fear in the absence of HPC activity. Post-learning inactivation of the HPC did not affect the establishment of a HPC-independent context memory. These results favor the idea that at least one memory system outside the HPC can acquire context memories independently. PMID:23201356

  2. Studies on Electrical Activation of Porcine Oocytes Matured in vitro and Embryo Culture Systems

    Institute of Scientific and Technical Information of China (English)

    WU Zhong-hong; XING Feng-ying; LIU Guo-shi; ZENG Shen-ming; ZHU Shi-en; ZHANG Zhong-cheng; FU Peng-hui

    2002-01-01

    Conditions for electrical parthenogenetic activation of porcine oocytes matured in vitro and in vitro culture systems of porcine embryo were studied. The best results were achieved under the conditions of electrical field strength and the pulse duration at 130Vmm-1/80 μs, with a blastocyst development rate of (20.12 ± 8.18)% (P > 0.05). No significant difference was found between treatments of multiple pulses and a single pulse ( P > 0.05). Parthenogenetic embryos were cultured with different methods and air conditions for 7 days in vitro, blastocyst development rate of embryos with changed culture media [ (26.44 ± 8.35)% ] or changed media with 10% fetal bovine serum (FBS) [ (17.68 ± 5.39)% ] on the fifth day showing no significant difference from that of embryos without change of culture media [ (25.30 ± 7.55) %, P > 0.05 ], while cell numbers of blastocysts from embryos with changed culture media (15.78 ± 5.46 and 14.55 ± 4.81) were significantly lower than number of blastocysts from embryos without change of culture media (18.01 ± 6.79,P < 0.01 ). Blastocyst development rate and blastocyst cell number of embryos cultured in lower O2 (5 % CO2:7%O2:88%N2) also showed no significant difference from those in high O2 (5% CO2 in air) [ (20.78 ± 8.80) % and 17.00 ± 6.12 vs. (25.30 ± 7.55) % and 18.01 ± 6.79, P > 0.05 ]. It is concluded that change of culture media with the same new one or changing over to media with 10% fetal bovine serum (FBS) on the fifth day and low O2 environment are not necessary for porcine embryos development.

  3. Activization of Investment Activity in the Culture Sphere as One of the Criteria for Ensuring the Investment Security of Ukraine

    Directory of Open Access Journals (Sweden)

    Revak Iryna O.

    2016-05-01

    Full Text Available The aim of the article is to study the trends in activization of investments into the culture sphere as one of the criteria of economic growth and ensuring the state investment security. Analyzing successful international experience and systematizing scientific research in this field it was determined that the development of the culture sphere contributes to growth of national productivity and improves the life quality of the population. On the basis of the study of socio-economic trends and statistical data there have been identified the development problems of the Ukrainian culture as a tool for transition to an innovative model of society development. The attention is focused on practical aspects of revival and maintaining a proper state of the cultural heritage of Ukraine as a source of provision of Ukrainian historical symbols, public morals and ethics. As a result of the research it is found that the objects of cultural heritage are the undisputed economic benefit, which has a direct impact on the investment attractiveness of regions.

  4. Hippocampal signatures of episodic memory: Evidence from single-unit recording studies

    Directory of Open Access Journals (Sweden)

    Amy L Griffin

    2013-05-01

    Full Text Available What hippocampal neural firing patterns signal memory and, more importantly, how is this memory code used by associated structures to translate a memory into a decision or action? Candidate hippocampal activity patterns will be discussed including (1 trajectory-specific firing of place cells with place fields on an overlapping segment of two (or more distinct trajectories (2 prospective firing of hippocampal neurons that signal an upcoming event or action, and (3 place cell remapping to changes in environment and task. To date, there has not compelling evidence for any of these activity patterns being the neural substrate of episodic memory. New findings suggest that learning and memory processes are emergent properties of interregional interactions and not localized within any one discrete brain region. Therefore, the next step in understanding how remapping and trajectory coding participate in memory coding may be to investigate how these activity patterns relate to activity in anatomically-connected structures such as the prefrontal cortex.

  5. Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication

    International Nuclear Information System (INIS)

    Melanoma is the most aggressive form of skin cancer, and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have been uniformly disappointing. A Brazilian complex homeopathic medication (CHM), used as an immune modulator, has been recommended for patients with depressed immune systems. Previous studies in mice have demonstrated that the CHM activates macrophages, induces an increase in the number of leukocytes and improves the murine response against Sarcoma-180. Here we studied the interaction of mouse lymph node lymphocytes, co-cultured in vitro with macrophages in the presence or absence of the CHM, with B16F10 melanoma cells. Lymphocytes co-cultured with macrophages in the presence of the CHM had greater anti-melanoma activity, reducing melanoma cell density and increasing the number of lysed tumor cells. There was also a higher proportion of activated (CD25+) lymphocytes with increased viability. Overall, lymphocytes activated by treatment destroyed growing cancer cells more effectively than control lymphocytes. Co-culture of macrophages with lymphocytes in the presence of the CHM enhanced the anti-cancer performance of lymphocytes against a very aggressive lineage of melanoma cells. These results suggest that non-toxic therapies using CHMs are a promising alternative approach to the treatment of melanomas. In addition, they are attractive combination-therapy candidates, which may enhance the efficacy of conventional medicines by improving the immune response against tumor cells

  6. Sertraline behavioral response associates closer and dose-dependently with cortical rather than hippocampal serotonergic activity in the rat forced swim stress.

    Science.gov (United States)

    Mikail, Hudu G; Dalla, Christina; Kokras, Nikolaos; Kafetzopoulos, Vasilios; Papadopoulou-Daifoti, Z

    2012-09-10

    The rat Forced Swim Test (FST) is widely used to investigate the response to antidepressant treatment. Selective serotonin reuptake inhibitors (SSRIs) elongate swimming duration during the FST, while climbing duration is unaffected. In the present study, we aimed to correlate behavioral effects of the SSRI sertraline in the FST with respective changes in the serotonergic activity of the hippocampus and the prefrontal cortex. Male rats were subjected to the standard FST (two swim sessions in two consecutive days) and between the two sessions they received three i.p. injections of sertraline (10 mg/kg or 40 mg/kg) or vehicle. All rats were killed immediately after the second FST session. Unstressed animals received the same administration schemes and were killed in equivalent time-points. Serotonin and its metabolite 5-HIAA were assayed in the hippocampus and the prefrontal cortex with the use of high-performance liquid chromatography (HPLC-ED) and their ratio 5-HIAA/5-HT was calculated. Sertraline enhanced swimming and decreased immobility duration at both doses. Serotonergic activity was not altered by the 2-day swim stress in either brain region, while subchronic sertraline treatment enhanced 5-HT levels and decreased 5-HIAA/5-HT in the hippocampus and the prefrontal cortex. The serotonin turnover rate (5-HIAA/5-HT ratio) decrease is probably indicative of reduced 5-HT metabolism, as a result of 5-HT reuptake inhibition. This effect was significant in the prefrontal cortex of unstressed rats only after a higher dose of sertraline. In the prefrontal cortex, but not in the hippocampus, immobility duration was negatively correlated with 5-HT tissue levels, whereas swimming duration was positively correlated with 5-HT. These results indicate that after antidepressant treatment, behavior during the FST can be predictive of respective serotonergic changes, especially in the prefrontal cortex.

  7. Hippocampal Context Processing during Acquisition of a Predictive Learning Task Is Associated with Renewal in Extinction Recall.

    Science.gov (United States)

    Lissek, Silke; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Tegenthoff, Martin

    2016-05-01

    Renewal is defined as the recovery of an extinguished response if extinction and retrieval contexts differ. The context dependency of extinction, as demonstrated by renewal, has important implications for extinction-based therapies. Persons showing renewal (REN) exhibit higher hippocampal activation during extinction in associative learning than those without renewal (NOREN), demonstrating hippocampal context processing, and recruit ventromedial pFC in retrieval. Apart from these findings, brain processes generating renewal remain largely unknown. Conceivably, processing differences in task-relevant brain regions that ultimately lead to renewal may occur already in initial acquisition of associations. Therefore, in two fMRI studies, we investigated overall brain activation and hippocampal activation in REN and NOREN during acquisition of an associative learning task in response to presentation of a context alone or combined with a cue. Results of two studies demonstrated significant activation differences between the groups: In Study 1, a support vector machine classifier correctly assigned participants' brain activation patterns to REN and NOREN groups, respectively. In Study 2, REN and NOREN showed similar hippocampal involvement during context-only presentation, suggesting processing of novelty, whereas overall hippocampal activation to the context-cue compound, suggesting compound encoding, was higher in REN. Positive correlations between hippocampal activation and renewal level indicated more prominent hippocampal processing in REN. Results suggest that hippocampal processing of the context-cue compound rather than of context only during initial learning is related to a subsequent renewal effect. Presumably, REN participants use distinct encoding strategies during acquisition of context-related tasks, which reflect in their brain activation patterns and contribute to a renewal effect. PMID:26807840

  8. Hippocampal CA1 Ripples as Inhibitory Transients.

    Science.gov (United States)

    Malerba, Paola; Krishnan, Giri P; Fellous, Jean-Marc; Bazhenov, Maxim

    2016-04-01

    Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network. PMID:27093059

  9. Hippocampal CA1 Ripples as Inhibitory Transients.

    Directory of Open Access Journals (Sweden)

    Paola Malerba

    2016-04-01

    Full Text Available Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.

  10. Bisphenol-A rapidly promotes dynamic changes in hippocampal dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDA receptor subunit NR2B

    International Nuclear Information System (INIS)

    Bisphenol-A (BPA) is known to be a potent endocrine disrupter. Evidence is emerging that estrogen exerts a rapid influence on hippocampal synaptic plasticity and the dendritic spine density, which requires activation of NMDA receptors. In the present study, we investigated the effects of BPA (ranging from 1 to 1000 nM), focusing on the rapid dynamic changes in dendritic filopodia and the expressions of estrogen receptor (ER) β and NMDA receptor, as well as the phosphorylation of NMDA receptor subunit NR2B in the cultured hippocampal neurons. A specific ER antagonist ICI 182,780 was used to examine the potential involvement of ERs. The results demonstrated that exposure to BPA (ranging from 10 to 1000 nM) for 30 min rapidly enhanced the motility and the density of dendritic filopodia in the cultured hippocampal neurons, as well as the phosphorylation of NR2B (pNR2B), though the expressions of NMDA receptor subunits NR1, NR2B, and ERβ were not changed. The antagonist of ERs completely inhibited the BPA-induced increases in the filopodial motility and the number of filopodia extending from dendrites. The increased pNR2B induced by BPA (100 nM) was also completely eliminated. Furthermore, BPA attenuated the effects of 17β-estradiol (17β-E2) on the dendritic filopodia outgrowth and the expression of pNR2B when BPA was co-treated with 17β-E2. The present results suggest that BPA, like 17β-E2, rapidly results in the enhanced motility and density of dendritic filopodia in the cultured hippocampal neurons with the concomitant activation of NMDA receptor subunit NR2B via an ER-mediated signaling pathway. Meanwhile, BPA suppressed the enhancement effects of 17β-E2 when it coexists with 17β-E2. These results provided important evidence suggesting the neurotoxicity of the low levels of BPA during the early postnatal development of the brain.

  11. Ex vivo dissection of optogenetically activated mPFC and hippocampal inputs to neurons in the basolateral amygdala: implications for fear and emotional memory

    Directory of Open Access Journals (Sweden)

    Cora eHübner

    2014-03-01

    Full Text Available Many lines of evidence suggest that a reciprocally interconnected network comprising the amygdala, ventral hippocampus (vHC, and medial prefrontal cortex (mPFC participates in different aspects of the acquisition and extinction of conditioned fear responses and fear behavior. This could at least in part be mediated by direct connections from mPFC or vHC to amygdala to control amygdala activity and output. However, currently the interactions between mPFC and vHC afferents and their specific targets in the amygdala are still poorly understood. Here, we use an ex-vivo optogenetic approach to dissect synaptic properties of inputs from mPFC and vHC to defined neuronal populations in the basal amygdala (BA, the area that we identify as a major target of these projections. We find that BA principal neurons (PNs and local BA interneurons (INs receive monosynaptic excitatory inputs from mPFC and vHC. In addition, both these inputs also recruit GABAergic feedforward inhibition in a substantial fraction of PNs, in some neurons this also comprises a slow GABAB-component. Amongst the innervated PNs we identify neurons that project back to subregions of the mPFC, indicating a loop between neurons in mPFC and BA, and a pathway from vHC to mPFC via BA. Interestingly, mPFC inputs also recruit feedforward inhibition in a fraction of INs, suggesting that these inputs can activate dis-inhibitory circuits in the BA. A general feature of both mPFC and vHC inputs to local INs is that excitatory inputs display faster rise and decay kinetics than in PNs, which would enable temporally precise signaling. However, mPFC and vHC inputs to both PNs and INs differ in their presynaptic release properties, in that vHC inputs are more depressing. In summary, our data describe novel wiring, and features of synaptic connections from mPFC and vHC to amygdala that could help to interpret functions of these interconnected brain areas at the network level.

  12. SOCIAL AND CULTURAL ACTIVITIES WITH PEOPLE OF THE THIRD AGE TO OVERCOME THE SOCIAL EXCLUSION: A REGIONAL PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Elena V. Kharkovskaya

    2016-06-01

    Full Text Available Introduction: this paper discusses the specifics of socio-cultural activities with people of the third age to overcome the social exclusion, identifies reasons for the decline of alienation level in this category of citizens in conditions of activity of cultural institutions. Materials and Methods: the authors’ findings are based on the philosophical, sociological, cultural, psychological and pedagogical literature and research methodology: observation, survey and content analysis. Results: the most effective methods of social and cultural activities in terms of overcoming the social exclusion of people of the third age were developed and experimentally tested. The main objective of the research was to examine the problems of exclusion among persons of the third age, as well as the possibilities of using social and cultural activities to overcome the social exclusion. In the paper the authors analyse the regional approach to the organisation of social and cultural activities of the elderly in institutions of social and cultural sphere. On the basis of the study the authors propose to extend and modify the variety of forms of leisure and intensify their use in working with people of the third age to overcome the social exclusion of an individual. All work on social and cultural activities with the elderly should be aimed primarily at optimising the social inclusion of elderly in society. Discussion and Conclusions: organisation of social and cultural activities for the elderly is a host of opportunities for the realisation of creative ideas. It is these new approaches to the activities of cultural institution’s collective that help to enhance the interaction between cultural institutions employees and retirees. This study is not exhaustive and does not finalise the research into the role of social and cultural activities as a condition for overcoming the social exclusion of people of the third age. This topic needs further exploration.

  13. Students’ Evaluation of Google Hangouts Through A Cross-Cultural Group Discussion Activity

    Directory of Open Access Journals (Sweden)

    Michiko KOBAYASHI

    2015-04-01

    Full Text Available The study investigated perceived ease of use and usefulness of Google Hangouts as an instructional/learning tool. Forty-two teacher education students at U.S and Japanese universities participated in an online cross-cultural activity using Google Hangouts and discussed cultural differences between the two countries and their teaching philosophies. After the activity, students responded to a survey to evaluate the ease of use and usefulness of Google Hangouts. Qualitative data were also collected through the survey to examine their overall learning experience. The results indicated that Google Hangouts is a useful instructional tool, but not easy to use. Although technical problems occurred during the conference, the activity provided valuable experiences for both U.S. and Japanese students. The study provides suggestions for how Google Hangouts can be integrated into online classrooms based on the findings.

  14. The tissue plasminogen activator (tPA)/plasmin extracellular proteolytic system regulates seizure-induced hippocampal mossy fiber outgrowth through a proteoglycan substrate.

    Science.gov (United States)

    Wu, Y P; Siao, C J; Lu, W; Sung, T C; Frohman, M A; Milev, P; Bugge, T H; Degen, J L; Levine, J M; Margolis, R U; Tsirka, S E

    2000-03-20

    Short seizure episodes are associated with remodeling of neuronal connections. One region where such reorganization occurs is the hippocampus, and in particular, the mossy fiber pathway. Using genetic and pharmacological approaches, we show here a critical role in vivo for tissue plasminogen activator (tPA), an extracellular protease that converts plasminogen to plasmin, to induce mossy fiber sprouting. We identify DSD-1-PG/phosphacan, an extracellular matrix component associated with neurite reorganization, as a physiological target of plasmin. Mice lacking tPA displayed decreased mossy fiber outgrowth and an aberrant band at the border of the supragranular region of the dentate gyrus that coincides with the deposition of unprocessed DSD-1-PG/phosphacan and excessive Timm-positive, mossy fiber termini. Plasminogen-deficient mice also exhibit the laminar band and DSD- 1-PG/phosphacan deposition, but mossy fiber outgrowth through the supragranular region is normal. These results demonstrate that tPA functions acutely, both through and independently of plasmin, to mediate mossy fiber reorganization.

  15. Cultured Neural Networks: Optimization of Patterned Network Adhesiveness and Characterization of their Neural Activity

    Directory of Open Access Journals (Sweden)

    W. L. C. Rutten

    2006-01-01

    Full Text Available One type of future, improved neural interface is the “cultured probe”. It is a hybrid type of neural information transducer or prosthesis, for stimulation and/or recording of neural activity. It would consist of a microelectrode array (MEA on a planar substrate, each electrode being covered and surrounded by a local circularly confined network (“island” of cultured neurons. The main purpose of the local networks is that they act as biofriendly intermediates for collateral sprouts from the in vivo system, thus allowing for an effective and selective neuron–electrode interface. As a secondary purpose, one may envisage future information processing applications of these intermediary networks. In this paper, first, progress is shown on how substrates can be chemically modified to confine developing networks, cultured from dissociated rat cortex cells, to “islands” surrounding an electrode site. Additional coating of neurophobic, polyimide-coated substrate by triblock-copolymer coating enhances neurophilic-neurophobic adhesion contrast. Secondly, results are given on neuronal activity in patterned, unconnected and connected, circular “island” networks. For connected islands, the larger the island diameter (50, 100 or 150 μm, the more spontaneous activity is seen. Also, activity may show a very high degree of synchronization between two islands. For unconnected islands, activity may start at 22 days in vitro (DIV, which is two weeks later than in unpatterned networks.

  16. SCHOOL, CULTURE & MOVEMENT : SUBJECTS/ACTORS FACE THE TRACES OF THEIR OWN ACTIVITY WHEN CREATING ALBUMS

    Directory of Open Access Journals (Sweden)

    Nadine Pairis

    2015-04-01

    Full Text Available This article concerns pupils' activity operated from the theoretical and methodological framework of data analysis of the "process of action" (Theureau, 2004 supporting on activity tracks (what emerges from the pre-reflexive consciousness and video recordings proceeded with individual interviews questioning the actors about their work : creation of albums into two classes of cycle 2 (one of them is an experimental artistic and cultural educational classroom with the help of an author/illustrator. The understanding of pupil’s activity answers the hypothesis of getting to work with creativity (Vygotski, 1930 in studying the "school well-being", the discourse analysis (case of Ramone who, in 2013, is not involved in the album creation while in 2014 he does not want to go out for a break before having finished the activity of visual art as well as the posture of their bodies at a moment of attentive listening. The results reveal that pupils need more movement than being in stand by (Jorro, 2013; Dewey 1934, in exploring their relationship to the space children become aware of the other ones (action vs passivity. The analysis of the pupils’ activity puts into perspective the impact of the artistic and cultural practices on learnings and movement (performance of their musical tale -moving in space with big-sized illustrations-, graphic movement : not only in writing but in positioning their body to accustom them to feel it before it hurts them as means of expression and cultural fact.

  17. Network synchronization in hippocampal neurons.

    Science.gov (United States)

    Penn, Yaron; Segal, Menahem; Moses, Elisha

    2016-03-22

    Oscillatory activity is widespread in dynamic neuronal networks. The main paradigm for the origin of periodicity consists of specialized pacemaking elements that synchronize and drive the rest of the network; however, other models exist. Here, we studied the spontaneous emergence of synchronized periodic bursting in a network of cultured dissociated neurons from rat hippocampus and cortex. Surprisingly, about 60% of all active neurons were self-sustained oscillators when disconnected, each with its own natural frequency. The individual neuron's tendency to oscillate and the corresponding oscillation frequency are controlled by its excitability. The single neuron intrinsic oscillations were blocked by riluzole, and are thus dependent on persistent sodium leak currents. Upon a gradual retrieval of connectivity, the synchrony evolves: Loose synchrony appears already at weak connectivity, with the oscillators converging to one common oscillation frequency, yet shifted in phase across the population. Further strengthening of the connectivity causes a reduction in the mean phase shifts until zero-lag is achieved, manifested by synchronous periodic network bursts. Interestingly, the frequency of network bursting matches the average of the intrinsic frequencies. Overall, the network behaves like other universal systems, where order emerges spontaneously by entrainment of independent rhythmic units. Although simplified with respect to circuitry in the brain, our results attribute a basic functional role for intrinsic single neuron excitability mechanisms in driving the network's activity and dynamics, contributing to our understanding of developing neural circuits.

  18. Activation of Hippocampal CREB by Rolipram Partially Recovers Balance Between TNF-α and IL-10 Levels and Improves Cognitive Deficits in Diabetic Rats.

    Science.gov (United States)

    Miao, Ya; He, Ting; Zhu, Yitong; Li, Wei; Wang, Beiyuan; Zhong, Yuan

    2015-11-01

    Diabetes damages the central nervous system, inducing cognitive dysfunction and structural changes, known as diabetic encephalopathy (DE). Some research suggests that the pathogenesis of DE may involve an inflammatory imbalance in the nervous system, along with β-amyloid deposition, similar to Alzheimer's disease. Less data have been yet provided to prove that mechanism. The aim of this study was to evaluate the influence of diabetes on the expression of TNF-α, IL-10, and cAMP response element-binding protein (CREB)/phosphorylated CREB (pCREB). Moreover, we investigated whether rolipram can improve memory, suppress the inflammatory response, and improve balance of CREB/pCREB in the hippocampus of diabetic rats. We used a 4-week high-fat diet and a low dose of streptozocin (30 mg/kg) to induce diabetes with hyperinsulinemia and hyperglycemia. Cognitive impairment was induced over a period of 4 months, and rolipram treatment was concomitantly given. Cognitive impairment was evaluated with the Morris water maze test. We also assessed expression of the pro-inflammatory cytokine TNF-α and the anti-inflammatory cytokine IL-10. We found that memory in rats with long-term diabetes was impaired. Treatment with rolipram increased expression of CREB and pCREB, reduced the inflammatory reaction (decreased TNF-α levels and increased IL-10 levels), and prevented cognitive impairment in these diabetic animals. This present study suggests that rolipram improves cognitive function by activating the CREB signaling pathway and alleviating neuroinflammation in type 2 diabetic rats. Rolipram may have therapeutic potential in DE. PMID:26001770

  19. Neural progenitor cell apoptosis and differentiation were affected by activated microglia in spinal cord slice culture.

    Science.gov (United States)

    Liu, Xuqing; Chu, Tak-Ho; Su, Huanxing; Guo, Anchen; Wu, Wutian

    2014-03-01

    Neural progenitor cell (NPC) transplantation offers great potential to treat spinal cord injury (SCI). NPCs may replace lost neurons or oligodendrocytes and act as a source of neurotrophic factors to support survival of remaining cells. However, their efficiency was limited by poor survival after transplantation, and they tended more to differentiate into astrocytes, but not neurons and oligodendrocytes. This study investigated whether activated microglia is a factor that contributes to this phenomenon. Organotypic spinal cord slice (SCS) culture was used to mimic the local environment after SCI, and NPCs were co-cultured with them to share the culture medium. After specific depletion of microglia in the SCSs with clodronate loaded liposome, the apoptotic rate of NPCs decreased, more NPCs differentiated into neurons, and glial differentiation was impaired. This suggested that microglia may impair NPC survival, and neuronal differentiation, but improve astrocyte differentiation. In NPC transplantation strategy for SCI, microglia would be manipulated to improve the survival and neuronal differentiation of NPCs.

  20. Linguistic neighbourhoods: explaining cultural borders on Wikipedia through multilingual co-editing activity

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    Samoilenko, Anna; Edler, Daniel; Kunegis, Jérôme; Strohmaier, Markus

    2016-01-01

    In this paper, we study the network of global interconnections between language communities, based on shared co-editing interests of Wikipedia editors, and show that although English is discussed as a potential lingua franca of the digital space, its domination disappears in the network of co-editing similarities, and instead local connections come to the forefront. Out of the hypotheses we explored, bilingualism, linguistic similarity of languages, and shared religion provide the best explanations for the similarity of interests between cultural communities. Population attraction and geographical proximity are also significant, but much weaker factors bringing communities together. In addition, we present an approach that allows for extracting significant cultural borders from editing activity of Wikipedia users, and comparing a set of hypotheses about the social mechanisms generating these borders. Our study sheds light on how culture is reflected in the collective process of archiving knowledge on Wikipedi...