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Sample records for bdnf transport defect

  1. Cerebral 5-HT2A receptor and serotonin transporter binding in humans are not affected by the val66met BDNF polymorphism status or blood BDNF levels

    DEFF Research Database (Denmark)

    Klein, Anders Bue; Trajkovska, Viktorija; Erritzoe, David; Haugbol, Steven; Madsen, Jacob; Baaré, William; Aznar, Susana; Knudsen, Gitte M

    2010-01-01

    Recent studies have proposed an interrelation between the brain-derived neurotrophic factor (BDNF) val66met polymorphism and the serotonin system. In this study, we investigated whether the BDNF val66met polymorphism or blood BDNF levels are associated with cerebral 5-hydroxytryptamine 2A (5-HT(2A...... BDNF polymorphism status is not associated with changes in the serotonergic system. Moreover, BDNF levels in blood do not correlate with either 5-HT(2A) or SERT binding.......)) receptor or serotonin transporter (SERT) binding in healthy subjects. No statistically significant differences in 5-HT(2A) receptor or SERT binding were found between the val/val and met carriers, nor were blood BDNF values associated with SERT binding or 5-HT(2A) receptor binding. In conclusion, val66met...

  2. Serine biosynthesis and transport defects.

    Science.gov (United States)

    El-Hattab, Ayman W

    2016-07-01

    l-serine is a non-essential amino acid that is biosynthesized via the enzymes phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). Besides its role in protein synthesis, l-serine is a potent neurotrophic factor and a precursor of a number of essential compounds including phosphatidylserine, sphingomyelin, glycine, and d-serine. Serine biosynthesis defects result from impairments of PGDH, PSAT, or PSP leading to systemic serine deficiency. Serine biosynthesis defects present in a broad phenotypic spectrum that includes, at the severe end, Neu-Laxova syndrome, a lethal multiple congenital anomaly disease, intermediately, infantile serine biosynthesis defects with severe neurological manifestations and growth deficiency, and at the mild end, the childhood disease with intellectual disability. A serine transport defect resulting from deficiency of the ASCT1, the main transporter for serine in the central nervous system, has been recently described in children with neurological manifestations that overlap with those observed in serine biosynthesis defects. l-serine therapy may be beneficial in preventing or ameliorating symptoms in serine biosynthesis and transport defects, if started before neurological damage occurs. Herein, we review serine metabolism and transport, the clinical, biochemical, and molecular aspects of serine biosynthesis and transport defects, the mechanisms of these diseases, and the potential role of serine therapy. PMID:27161889

  3. Brain-derived neurotrophic factor (BDNF) enhances GABA transport by modulating the trafficking of GABA transporter-1 (GAT-1) from the plasma membrane of rat cortical astrocytes

    DEFF Research Database (Denmark)

    Vaz, Sandra H; Jørgensen, Trine Nygaard; Cristóvão-Ferreira, Sofia;

    2011-01-01

    /MAPK pathway and requires active adenosine A(2A) receptors. Transport through GAT-3 is not affected by BDNF. To elucidate if BDNF affects trafficking of GAT-1 in astrocytes, we generated and infected astrocytes with a functional mutant of the rat GAT-1 (rGAT-1) in which the hemagglutinin (HA) epitope was...

  4. Cerebral 5-HT2A receptor and serotonin transporter binding in humans are not affected by the val66met BDNF polymorphism status or blood BDNF levels

    DEFF Research Database (Denmark)

    Klein, Anders Bue; Trajkovska, Viktorija; Erritzoe, David;

    2010-01-01

    Recent studies have proposed an interrelation between the brain-derived neurotrophic factor (BDNF) val66met polymorphism and the serotonin system. In this study, we investigated whether the BDNF val66met polymorphism or blood BDNF levels are associated with cerebral 5-hydroxytryptamine 2A (5-HT(2...

  5. Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegeneration

    DEFF Research Database (Denmark)

    Ziebell, Morten; Khalid, Usman; Klein, Anders B;

    2012-01-01

    Compelling evidence has shown, that neurotrophins responsible for the regulation of neuronal growth, survival, and differentiation are involved in neurodegenerative diseases. Whereas lower serum levels of brain derived neurotrophic factor (BDNF) have been observed in patients with Parkinson's dis...

  6. Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade.

    Directory of Open Access Journals (Sweden)

    Tomi Rantamäki

    Full Text Available BACKGROUND: Antidepressant drugs (ADs have been shown to activate BDNF (brain-derived neurotrophic factor receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their neurotrophin ligands. METHODOLOGY: In this study we examined the role of BDNF, TrkB kinase activity and monoamine reuptake in the AD-induced TrkB activation in vivo and in vitro by employing several transgenic mouse models, cultured neurons and TrkB-expressing cell lines. PRINCIPAL FINDINGS: Using a chemical-genetic TrkB(F616A mutant and TrkB overexpressing mice, we demonstrate that ADs specifically activate both the maturely and immaturely glycosylated forms of TrkB receptors in the brain in a TrkB kinase dependent manner. However, the tricyclic AD imipramine readily induced the phosphorylation of TrkB receptors in conditional bdnf⁻/⁻ knock-out mice (132.4±8.5% of control; P = 0.01, indicating that BDNF is not required for the TrkB activation. Moreover, using serotonin transporter (SERT deficient mice and chemical lesions of monoaminergic neurons we show that neither a functional SERT nor monoamines are required for the TrkB phosphorylation response induced by the serotonin selective reuptake inhibitors fluoxetine or citalopram, or norepinephrine selective reuptake inhibitor reboxetine. However, neither ADs nor monoamine transmitters activated TrkB in cultured neurons or cell lines expressing TrkB receptors, arguing that ADs do not directly bind to TrkB. CONCLUSIONS: The present findings suggest that ADs transactivate brain TrkB receptors independently of BDNF and monoamine reuptake blockade and emphasize the need of an intact tissue context for the

  7. Transport properties of 2D graphene containing structural defects

    OpenAIRE

    Lherbier, Aurelien; Dubois, Simon M. -M.; Declerck, Xavier; Niquet, Yann-Michel; Roche, Stephan; Charlier, Jean-Christophe

    2012-01-01

    We propose an extensive report on the simulation of electronic transport in 2D graphene in presence of structural defects. Amongst the large variety of such defects in sp$^2$ carbon-based materials, we focus on the Stone-Wales defect and on two divacancy-type reconstructed defects. First, based on ab initio calculations, a tight-binding model is derived to describe the electronic structure of these defects. Then, semiclassical transport properties including the elastic mean free paths, mobili...

  8. Family-based association study of the BDNF, COMT and serotonin transporter genes and DSM-IV bipolar-I disorder in children

    Directory of Open Access Journals (Sweden)

    Biederman Joseph

    2009-02-01

    Full Text Available Abstract Background Over the past decade pediatric bipolar disorder has gained recognition as a potentially more severe and heritable form of the disorder. In this report we test for association with genes coding brain-derived neurotrophic factor (BDNF, the serotonin transporter (SLC6A4, and catechol-O-methyltransferase (COMT. Methods Bipolar-I affected offspring triads (N = 173 were drawn from 522 individuals with 2 parents in 332 nuclear families recruited for genetic studies of pediatric psychopathology at the Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital. Results We failed to identify an association with the val66 allele in BDNF (OR = 1.23, p = 0.36, the COMT-l allele (OR = 1.27, p = 0.1, or the HTTLPR short allele (OR = 0.87, p = 0.38. Conclusion Our study suggests that the markers examined thus far in COMT and SLC6A4 are not associated with pediatric bipolar disorder and that if the val66met marker in BDNF is associated with pediatric bipolar disorder the magnitude of the association is much smaller than first reported.

  9. Consequences of changes in BDNF levels on serotonin neurotransmission, 5-HT transporter expression and function: studies in adult mice hippocampus.

    Science.gov (United States)

    Deltheil, Thierry; Guiard, Bruno P; Guilloux, Jean-Philippe; Nicolas, Lorelei; Deloménie, Claudine; Repérant, Christelle; Le Maitre, Erwan; Leroux-Nicollet, Isabelle; Benmansour, Saloua; Coudoré, François; David, Denis J; Gardier, Alain M

    2008-08-01

    In vivo intracerebral microdialysis is an important neurochemical technique that has been applied extensively in genetic and pharmacological studies aimed at investigating the relationship between neurotransmitters. Among the main interests of microdialysis application is the infusion of drugs through the microdialysis probe (reverse dialysis) in awake, freely moving animals. As an example of the relevance of intracerebral microdialysis, this review will focus on our recent neurochemical results showing the impact of Brain-Derived Neurotrophic Factor (BDNF) on serotonergic neurotransmission in basal and stimulated conditions. Indeed, although the elevation of 5-HT outflow induced by chronic administration of selective serotonin reuptake inhibitors (SSRIs) causes an increase in BDNF protein levels and expression (mRNA) in the hippocampus of rodents, the reciprocal interaction has not been demonstrated yet. Thus, the neurochemical sight of this question will be addressed here by examining the consequences of either a constitutive decrease or increase in brain BDNF protein levels on hippocampal extracellular levels of 5-HT in conscious mice. PMID:17980409

  10. The Effects of Oxytocin on Cognitive Defect Caused by Chronic Restraint Stress Applied to Adolescent Rats and on Hippocampal VEGF and BDNF Levels

    OpenAIRE

    Dayi, Ayfer; Cetin, Ferihan; Sisman, Ali Riza; Aksu, Ilkay; Tas, Aysegul; Gönenc, Sevil; Uysal, Nazan

    2015-01-01

    Background Because brain development continues during adolescence, the effects of chronic stress on hippocampal changes that occur during that period are permanent. Oxytocin, which is synthesized in the hypothalamus and has many receptors in brain regions, including the hippocampus, may affect learning-memory. This study aimed to investigate chronic restraint stress on hippocampal functions, and hippocampal vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF)...

  11. A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP.

    Directory of Open Access Journals (Sweden)

    April M Weissmiller

    Full Text Available Clues to Alzheimer disease (AD pathogenesis come from a variety of different sources including studies of clinical and neuropathological features, biomarkers, genomics and animal and cellular models. An important role for amyloid precursor protein (APP and its processing has emerged and considerable interest has been directed at the hypothesis that Aβ peptides induce changes central to pathogenesis. Accordingly, molecules that reduce the levels of Aβ peptides have been discovered such as γ-secretase inhibitors (GSIs and modulators (GSMs. GSIs and GSMs reduce Aβ levels through very different mechanisms. However, GSIs, but not GSMs, markedly increase the levels of APP CTFs that are increasingly viewed as disrupting neuronal function. Here, we evaluated the effects of GSIs and GSMs on a number of neuronal phenotypes possibly relevant to their use in treatment of AD. We report that GSI disrupted retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF, suppressed BDNF-induced downstream signaling pathways and induced changes in the distribution within neuronal processes of mitochondria and synaptic vesicles. In contrast, treatment with a novel class of GSMs had no significant effect on these measures. Since knockdown of APP by specific siRNA prevented GSI-induced changes in BDNF axonal trafficking and signaling, we concluded that GSI effects on APP processing were responsible, at least in part, for BDNF trafficking and signaling deficits. Our findings argue that with respect to anti-amyloid treatments, even an APP-specific GSI may have deleterious effects and GSMs may serve as a better alternative.

  12. Defect engineering of the electronic transport through cuprous oxide interlayers

    Science.gov (United States)

    Fadlallah, Mohamed M.; Eckern, Ulrich; Schwingenschlögl, Udo

    2016-06-01

    The electronic transport through Au–(Cu2O)n–Au junctions is investigated using first-principles calculations and the nonequilibrium Green’s function method. The effect of varying the thickness (i.e., n) is studied as well as that of point defects and anion substitution. For all Cu2O thicknesses the conductance is more enhanced by bulk-like (in contrast to near-interface) defects, with the exception of O vacancies and Cl substitutional defects. A similar transmission behavior results from Cu deficiency and N substitution, as well as from Cl substitution and N interstitials for thick Cu2O junctions. In agreement with recent experimental observations, it is found that N and Cl doping enhances the conductance. A Frenkel defect, i.e., a superposition of an O interstitial and O substitutional defect, leads to a remarkably high conductance. From the analysis of the defect formation energies, Cu vacancies are found to be particularly stable, in agreement with earlier experimental and theoretical work.

  13. Defect engineering of the electronic transport through cuprous oxide interlayers

    KAUST Repository

    Fadlallah, Mohamed M.

    2016-06-03

    The electronic transport through Au–(Cu2O)n–Au junctions is investigated using first-principles calculations and the nonequilibrium Green’s function method. The effect of varying the thickness (i.e., n) is studied as well as that of point defects and anion substitution. For all Cu2O thicknesses the conductance is more enhanced by bulk-like (in contrast to near-interface) defects, with the exception of O vacancies and Cl substitutional defects. A similar transmission behavior results from Cu deficiency and N substitution, as well as from Cl substitution and N interstitials for thick Cu2O junctions. In agreement with recent experimental observations, it is found that N and Cl doping enhances the conductance. A Frenkel defect, i.e., a superposition of an O interstitial and O substitutional defect, leads to a remarkably high conductance. From the analysis of the defect formation energies, Cu vacancies are found to be particularly stable, in agreement with earlier experimental and theoretical work.

  14. Intercalary bone segment transport in treatment of segmental tibial defects

    International Nuclear Information System (INIS)

    Objective: To evaluate the results and complications of intercalary bone segment transport in the treatment of segmental tibial defects. Design: This is a retrospective analysis of patients with segmental tibial defects who were treated with intercalary bone segment transport method. Place and Duration of Study: The study was carried out at Combined Military Hospital, Rawalpindi from September 1997 to April 2001. Subjects and methods: Thirteen patients were included in the study who had developed tibial defects either due to open fractures with bone loss or subsequent to bone debridement of infected non unions. The mean bone defect was 6.4 cms and there were eight associated soft tissue defects. Locally made unilateral 'Naseer-Awais' (NA) fixator was used for bone segment transport. The distraction was done at the rate of 1mm/day after 7-10 days of osteotomy. The patients were followed-up fortnightly during distraction and monthly thereafter. The mean follow-up duration was 18 months. Results: The mean time in external fixation was 9.4 months. The mean healing index' was 1.47 months/cm. Satisfactory union was achieved in all cases. Six cases (46.2%) required bone grafting at target site and in one of them grafting was required at the level of regeneration as well. All the wounds healed well with no residual infection. There was no residual leg length discrepancy of more than 20 mm nd one angular deformity of more than 5 degrees. The commonest complication encountered was pin track infection seen in 38% of Shanz Screws applied. Loosening occurred in 6.8% of Shanz screws, requiring re-adjustment. Ankle joint contracture with equinus deformity and peroneal nerve paresis occurred in one case each. The functional results were graded as 'good' in seven, 'fair' in four, and 'poor' in two patients. Overall, thirteen patients had 31 (minor/major) complications with a ratio of 2.38 complications per patient. To treat the bone defects and associated complications, a mean of 3

  15. Defective fluid transport by cystic fibrosis airway epithelia.

    OpenAIRE

    Smith, J.J.; Karp, P H; Welsh, M J

    1994-01-01

    Cystic fibrosis (CF) airway epithelia exhibit defective transepithelial electrolyte transport: cAMP-stimulated Cl- secretion is abolished because of the loss of apical membrane cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels, and amiloride-sensitive Na+ absorption is increased two- to threefold because of increased amiloride-sensitive apical Na+ permeability. These abnormalities are thought to alter respiratory tract fluid, thereby contributing to airway disease, the m...

  16. Atomistic simulations of divacancy defects in armchair graphene nanoribbons: Stability, electronic structure, and electron transport properties

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jun [College of Physical Science and Technology, Yangtze University, Jingzhou, Hubei 434023 (China); Zeng, Hui, E-mail: zenghui@yangtzeu.edu.cn [College of Physical Science and Technology, Yangtze University, Jingzhou, Hubei 434023 (China); Wei, Jianwei [College of Optoelectronic Information, Chongqing University of Technology, Chongqing 400054 (China); Li, Biao; Xu, Dahai [College of Physical Science and Technology, Yangtze University, Jingzhou, Hubei 434023 (China)

    2014-01-17

    Using the first principles calculations associated with nonequilibrium Green's function, we have studied the electronic structures and quantum transport properties of defective armchair graphene nanoribbon (AGNR) in the presence of divacancy defects. The triple pentagon–triple heptagon (555–777) defect in the defective AGNR is energetically more favorable than the pentagon–octagon–pentagon (5–8–5) defect. Our calculated results reveal that both 5–8–5-like defect and 555–777-like defect in AGNR could improve the electron transport. It is anticipated that defective AGNRs can exhibit large range variations in transport behaviors, which are strongly dependent on the distributions of the divacancy defect.

  17. Transient carnitine transport defect with cholestatic jaundice: report of one case in a premature baby

    OpenAIRE

    Hyun-Seok Cho; Young Kwang Choo; Hong Jin Lee; hyeon-Soo Lee

    2012-01-01

    Carnitine (?#11112;ydroxy-?#15220;rimethylaminobutyric acid) is involved in the transport of long-chain fatty acids into the mitochondrial matrix and the removal of potentially toxic acylcarnitine esters. Transient carnitine transport defect is a rare condition in newborns reported in 1/90,000 live births. In this paper, we describe a case of transient carnitine transport defect found in a premature baby who had prolonged cholestatic jaundice and poor weight gain, and who responded dramat...

  18. Multiscale Defect Formation and Transport in Materials in Extreme Environments

    Science.gov (United States)

    Seif, Dariush

    In this dissertation, we develop computational models of point defect formation and transport in spatially heterogeneous stress and temperature fields. To accomplish this, first an atomistically-based description of point defects is developed using a combination of molecular statics calculations and continuum elasticity theory. This enables an accurate representation of point defect strain fields and their interaction energies in various strain fields. The continuum representation has been found to be accurate to within several percent of the atomistic calculations and was successfully tested against highly accurate first principles calculations in a published study. Using the described point defect representation, we have performed calculations of the dislocation bias factor for irradiated metals, using a spatially-resolved rate theory solution we developed based on the finite element method. The flexibility of the model is fully exploited, leading to calculations with heightened resolution; accounting for the spatially-dependent, energetically favorable SIA orientations, one-dimensional diffusion mechanisms near the dislocation core, and full anisotropic elasticity. Our results for iron have shown that the effects of preferred SIA orientations should not be ignored near the dislocation core. Implementing minimum energy SIA configurations in iron decreases repulsive interactions and increases absorption, ultimately leading to much larger bias factors. On the other hand, we also find the use of anisotropic elasticity in the calculations to decrease bias factors by 45% compared to those obtained using the isotropic formulation. An anisotropic implementation of the dislocation strain fields, however, gives larger interaction energy gradients, leading to increased drift diffusion and larger bias (12% and 6% increase in Fe and Cu, respectively). Following the rapid transient stage of helium-vacancy cluster (bubble) nucleation under irradiation, the bubble growth phase

  19. Localization of BDNF mRNA with the Huntington's disease protein in rat brain

    OpenAIRE

    Chao Moses V; Tongiorgi Enrico; Baj Gabriele; Culver Brady P; Ma Bin; Tanese Naoko

    2010-01-01

    Abstract Background Studies have implicated reduced levels of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Huntington's disease. Mutant huntingtin (Htt) protein was previously reported to decrease BDNF gene transcription and axonal transport of BDNF. We recently showed that wild-type Htt is associated with the Argonaute 2 microRNA-processing enzyme involved in gene silencing. In dendrites, Htt co-localizes with components of neuronal granules and mRNAs, indicating that it m...

  20. Final report. Defects and transport in mixed oxides

    Energy Technology Data Exchange (ETDEWEB)

    Dieckmann, R{umlt u}diger

    2001-12-13

    New results on the point defect chemistry of (Ni{sub x}Fe{sub 1-x}){sub 3-delta}O{sub 4} and on the cation tracer diffusion in this spinel solid solution are presented and discussed. The equation system for the defect chemistry of perovskites of the type A{sub 1-x}B{sub 1+x}O{sub 3-delta} have been worked out and used to derive Kr{umlt o}ger-Vink diagrams. The deviation from stoichiometry, delta, in LA{sub 1-x}Mn{sub 1+x}O{sub 3-delta} has been measured at 1100, 1200, and 1300 degrees Celsius as a function of the oxygen activity and the composition variable x. At high and low oxygen activities, the data were fit by taking into account the electrostatic interaction between the charge defects by making use of the Debye H{umlt u}ckel theory.

  1. Oxide-based protonic conductors: Point defects and transport properties

    DEFF Research Database (Denmark)

    Bonanos, N.

    , hydrogen pumps, fuel cells, etc. The extent to which protonic defects form depends mainly on the partial pressure of water vapour, temperature and basicity of the constituent oxides, while their mobility depends, among other factors, on the metal-oxygen bond length and bond energy. The defect equilibria...... that determine the protonic concentrations are considered, with emphasis on the regime of low oxygen partial pressure. The measurement of the thermoelectric power (TEP) and of the H+/D+ isotope effect in conductivity are discussed as a means of characterising the conduction process. (C) 2001 Elsevier...

  2. Oxide-based protonic conductors: Point defects and transport properties

    DEFF Research Database (Denmark)

    Bonanos, N.

    2001-01-01

    , hydrogen pumps, fuel cells, etc. The extent to which protonic defects form depends mainly on the partial pressure of water vapour, temperature and basicity of the constituent oxides, while their mobility depends, among other factors, on the metal-oxygen bond length and bond energy. The defect equilibria...... that determine the protonic concentrations are considered, with emphasis on the regime of low oxygen partial pressure. The measurement of the thermoelectric power (TEP) and of the H+/D+ isotope effect in conductivity are discussed as a means of characterising the conduction process. (C) 2001 Elsevier...

  3. Revealing origin of quasi-one dimensional current transport in defect rich two dimensional materials

    DEFF Research Database (Denmark)

    Lotz, Mikkel Rønne; Boll, Mads; Hansen, Ole;

    2014-01-01

    conductors with an increasing amount of line-shaped defects. Clear 2D and 1D signatures are observed at low and high defect densities, respectively, and current density plots reveal the presence of current channels or branches in defect configurations yielding 1D current transport. A strong correlation is...... found between the density filling factor and the simulation yield, the fraction of cases with 1D transport and the mean sheet conductance. The upper transition limit is shown to agree with the percolation threshold for sticks. Finally, the conductance of a square sample evaluated with macroscopic edge...

  4. Low temperature transport spectroscopy of defects using Schottky-barrier MOSFETs

    Energy Technology Data Exchange (ETDEWEB)

    Calvet, L.E., E-mail: laurie.calvet@u-psud.f [Institut d' Electronique Fondamentale-CNRS UMR 8622, Universite Paris-Sud, 91405 Orsay (France); Meshkov, G.A. [Department of Physics, M.V. Lomonosov Moscow State University, Leninskie gori, Moscow 119992 (Russian Federation); Strupiechonski, E.; Toubestani, D. [Institut d' Electronique Fondamentale-CNRS UMR 8622, Universite Paris-Sud, 91405 Orsay (France); Snyder, J.P. [Independent Consultant, Bloomington, MN 55425 (United States); Fortuna, F. [Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse-CNRS UMR 8609, Universite Paris-Sud, 91405 Orsay (France); Wernsdorfer, W. [Institut Neel, CNRS, BP 166, 25 Avenue des Martyrs, 38042 Grenoble Cedex 9 (France)

    2009-12-15

    An overview of our technique to explore single defects in silicon using a novel transistor geometry, the Schottky barrier MOSFET, is described. In this device the doped source and drain regions of a conventional MOSFET are replaced with metallic contacts. At low temperatures electron transport is dominated by direct tunneling through the space charge region formed next to the metal/semiconductor interface. If single impurities or defects are present in this region, transport reveals resonant tunneling peaks that allow investigations of the magnetic field dependence and excited states. Here we discuss different experiments where we have on separate occasions observed defects that may be related to Pt, B and Tb.

  5. Low temperature transport spectroscopy of defects using Schottky-barrier MOSFETs

    International Nuclear Information System (INIS)

    An overview of our technique to explore single defects in silicon using a novel transistor geometry, the Schottky barrier MOSFET, is described. In this device the doped source and drain regions of a conventional MOSFET are replaced with metallic contacts. At low temperatures electron transport is dominated by direct tunneling through the space charge region formed next to the metal/semiconductor interface. If single impurities or defects are present in this region, transport reveals resonant tunneling peaks that allow investigations of the magnetic field dependence and excited states. Here we discuss different experiments where we have on separate occasions observed defects that may be related to Pt, B and Tb.

  6. Localization of BDNF mRNA with the Huntington's disease protein in rat brain

    Directory of Open Access Journals (Sweden)

    Chao Moses V

    2010-05-01

    Full Text Available Abstract Background Studies have implicated reduced levels of brain-derived neurotrophic factor (BDNF in the pathogenesis of Huntington's disease. Mutant huntingtin (Htt protein was previously reported to decrease BDNF gene transcription and axonal transport of BDNF. We recently showed that wild-type Htt is associated with the Argonaute 2 microRNA-processing enzyme involved in gene silencing. In dendrites, Htt co-localizes with components of neuronal granules and mRNAs, indicating that it might play a role in post-transcriptional processing/transport of dendritic mRNAs. Results We conducted imaging experiments in cultured cortical neurons to demonstrate the co-localization of endogenous Htt and BDNF mRNA in fixed cells, and co-trafficking of BDNF 3'UTR mRNA with endogenous and fluorescently tagged Htt in live neurons. We used an enhanced technique that combines FISH and immunofluorescent staining to co-localize BDNF mRNA with Htt, Ago2, CPEB and dynein in thick vibratome sections of the rat cortex. Conclusions In cultured neurons and sections of the rat cortex, we found BDNF mRNA associated with Htt and components of neuronal RNA granules, which are centers for regulating RNA transport and local translation. Htt may play a role in post-transcriptional transport/targeting of mRNA for BDNF, thus contributing to neurotrophic support and neuron survival.

  7. Defect states and disorder in charge transport in semiconductor nanowires

    OpenAIRE

    Ko, Dongkyun; Zhao, X. W.; Reddy, Kongara M.; Restrepo, O. D.; Mishra, R; Beloborodov, I. S.; Trivedi, Nandini; Padture, Nitin P.; W. Windl; Yang, F. Y.; Johnston-Halperin, E.

    2011-01-01

    We present a comprehensive investigation into disorder-mediated charge transport in InP nanowires in the statistical doping regime. At zero gate voltage transport is well described by the space charge limited current model and Efros-Shklovskii variable range hopping, but positive gate voltage (electron accumulation) reveals a previously unexplored regime of nanowire charge transport that is not well described by existing theory. The ability to continuously tune between these regimes provides ...

  8. Transient carnitine transport defect with cholestatic jaundice: report of one case in a premature baby

    Directory of Open Access Journals (Sweden)

    Hyun-Seok Cho

    2012-02-01

    Full Text Available Carnitine (?#11112;ydroxy-?#15220;rimethylaminobutyric acid is involved in the transport of long-chain fatty acids into the mitochondrial matrix and the removal of potentially toxic acylcarnitine esters. Transient carnitine transport defect is a rare condition in newborns reported in 1/90,000 live births. In this paper, we describe a case of transient carnitine transport defect found in a premature baby who had prolonged cholestatic jaundice and poor weight gain, and who responded dramatically to oral carnitine supplementation.

  9. Enhanced tracer transport by the spiral defect chaos state of a convecting fluid

    OpenAIRE

    Chiam, K.-H.; Cross, M. C.; Greenside, H. S.; Fischer, P. F.

    2005-01-01

    To understand how spatiotemporal chaos may modify material transport, we use direct numerical simulations of the three-dimensional Boussinesq equations and of an advection-diffusion equation to study the transport of a passive tracer by the spiral defect chaos state of a convecting fluid. The simulations show that the transport is diffusive and is enhanced by the spatiotemporal chaos. The enhancement in tracer diffusivity follows two regimes. For large Peclet numbers (that is, small molecular...

  10. Transport-reaction model for defect and carrier behavior within displacement cascades in gallium arsenide

    Energy Technology Data Exchange (ETDEWEB)

    Wampler, William R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Myers, Samuel M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-02-01

    A model is presented for recombination of charge carriers at displacement damage in gallium arsenide, which includes clustering of the defects in atomic displacement cascades produced by neutron or ion irradiation. The carrier recombination model is based on an atomistic description of capture and emission of carriers by the defects with time evolution resulting from the migration and reaction of the defects. The physics and equations on which the model is based are presented, along with details of the numerical methods used for their solution. The model uses a continuum description of diffusion, field-drift and reaction of carriers and defects within a representative spherically symmetric cluster. The initial radial defect profiles within the cluster were chosen through pair-correlation-function analysis of the spatial distribution of defects obtained from the binary-collision code MARLOWE, using recoil energies for fission neutrons. Charging of the defects can produce high electric fields within the cluster which may influence transport and reaction of carriers and defects, and which may enhance carrier recombination through band-to-trap tunneling. Properties of the defects are discussed and values for their parameters are given, many of which were obtained from density functional theory. The model provides a basis for predicting the transient response of III-V heterojunction bipolar transistors to pulsed neutron irradiation.

  11. Relationship between defect density and charge carrier transport in amorphous and microcrystalline silicon

    OpenAIRE

    Astakhov, O.; Carius, R.; F. Finger; Petrusenko, Y.; Borysenko, V.; Barankov, D.

    2009-01-01

    The influence of dangling-bond defects and the position of the Fermi level on the charge carrier transport properties in undoped and phosphorous doped thin-film silicon with structure compositions all the way from highly crystalline to amorphous is investigated. The dangling-bond density is varied reproducibly over several orders of magnitude by electron bombardment and subsequent annealing. The defects are investigated by electron-spin-resonance and photoconductivity spectroscopies. Comparin...

  12. Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

    CERN Document Server

    Appert-Rolland, Cecile; Santen, Ludger

    2015-01-01

    Cells are strongly out-of-equilibrium systems driven by continuous energy supply. They carry out many vital functions requiring active transport of various ingredients and organelles, some being small, others being large. The cytoskeleton, composed of three types of filaments, determines the shape of the cell and plays a role in cell motion. It also serves as a road network for the so-called cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated, in particular because its breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. We first review some biological facts obtained from experiments, and present some modeling attempts based on cellular automata. We start with background knowledge on the origi...

  13. Defect chemistry of ''BaCuO2''. Pt. 2. Transport properties and nature of defects

    International Nuclear Information System (INIS)

    The charge transport properties of ''BaCuO2'' with 88:90 (Ba:Cu) cation ratio were characterized by thermopower, electrical conductivity and ionic transport number measurements in a wide range of temperature and oxygen partial pressure conditions. The nature of carriers is always represented by small polarons due to self-trapping of the electronic holes generated by the oxygen non-stoichiometry equilibrium. Some anomalies in carrier mobility as a function of temperature are shown not to be related to incomplete ionization of oxygen atoms on interstitial sites (orig.)

  14. Revealing origin of quasi-one dimensional current transport in defect rich two dimensional materials

    Energy Technology Data Exchange (ETDEWEB)

    Lotz, Mikkel R.; Boll, Mads; Bøggild, Peter; Petersen, Dirch H., E-mail: dirch.petersen@nanotech.dtu.dk [Center for Nanostructured Graphene (CNG), Department of Micro- and Nanotechnology, Technical University of Denmark, DTU Nanotech Building 345 East, DK-2800 Kgs. Lyngby (Denmark); Hansen, Ole [Department of Micro- and Nanotechnology, Technical University of Denmark, DTU Nanotech Building 345 East, DK-2800 Kgs. Lyngby (Denmark); Danish National Research Foundation' s Center for Individual Nanoparticle Functionality (CINF), Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark); Kjær, Daniel [Department of Micro- and Nanotechnology, Technical University of Denmark, DTU Nanotech Building 345 East, DK-2800 Kgs. Lyngby (Denmark); CAPRES A/S, Scion-DTU, Building 373, DK-2800 Kgs. Lyngby (Denmark)

    2014-08-04

    The presence of defects in graphene have for a long time been recognized as a bottleneck for its utilization in electronic and mechanical devices. We recently showed that micro four-point probes may be used to evaluate if a graphene film is truly 2D or if defects in proximity of the probe will lead to a non-uniform current flow characteristic of lower dimensionality. In this work, simulations based on a finite element method together with a Monte Carlo approach are used to establish the transition from 2D to quasi-1D current transport, when applying a micro four-point probe to measure on 2D conductors with an increasing amount of line-shaped defects. Clear 2D and 1D signatures are observed at low and high defect densities, respectively, and current density plots reveal the presence of current channels or branches in defect configurations yielding 1D current transport. A strong correlation is found between the density filling factor and the simulation yield, the fraction of cases with 1D transport and the mean sheet conductance. The upper transition limit is shown to agree with the percolation threshold for sticks. Finally, the conductance of a square sample evaluated with macroscopic edge contacts is compared to the micro four-point probe conductance measurements and we find that the micro four-point probe tends to measure a slightly higher conductance in samples containing defects.

  15. Spin- and valley-polarized transport across line defects in monolayer MoS2

    Science.gov (United States)

    Pulkin, Artem; Yazyev, Oleg V.

    2016-01-01

    We address the ballistic transmission of charge carriers across ordered line defects in monolayer transition metal dichalcogenides. Our study reveals the presence of a transport gap driven by spin-orbit interactions, spin and valley filtering, both stemming from a simple picture of spin and momentum conservation, as well as the electron-hole asymmetry of charge-carrier transmission. Electronic transport properties of experimentally observed ordered line defects in monolayer MoS2, in particular, the vacancy lines and inversion domain boundaries, are further investigated using first-principles Green's function methodology. Our calculations demonstrate the possibility of achieving nearly complete spin polarization of charge carriers in nanoelectronic devices based on engineered periodic line defects in monolayer transition metal dichalcogenides, thus suggesting a practical scheme for all-electric control of spin transport.

  16. Depression, 5HTTLPR and BDNF Val66Met polymorphisms, and plasma BDNF levels in hemodialysis patients with chronic renal failure

    Directory of Open Access Journals (Sweden)

    Wang LJ

    2014-07-01

    Full Text Available Liang-Jen Wang,1,* Chih-Ken Chen,2,3,* Heng-Jung Hsu,3,4 I-Wen Wu,3,4 Chiao-Yin Sun,3,4 Chin-Chan Lee3,41Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Psychiatry, Chang Gung Memorial Hospital, Keelung, Taiwan; 3Chang Gung University School of Medicine, Taoyuan, Taiwan; 4Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan *LJW and CKC are joint first authors and contributed equally to this manuscriptObjective: Depression is the most prevalent comorbid psychiatric disease among hemodialysis patients with end-stage renal disease. This cross-sectional study investigated whether depression in hemodialysis patients is associated with the polymorphism of the 5' flanking transcriptional region (5-HTTLPR of the serotonin transporter gene, the valine (Val-to-methionine (Met substitution at codon 66 (Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF gene, or plasma BDNF levels.Methods: A total of 188 participants (mean age: 58.5±14.0 years; 89 men and 99 women receiving hemodialysis at the Chang Gung Memorial Hospital were recruited. The diagnosis of major depressive disorder (MDD was confirmed using the Chinese version of the Mini International Neuropsychiatric Interview. The genotypes of 5-HTTLPR and BDNF Val66Met were conducted using polymerase chain reactions plus restriction fragment length polymorphism analysis. The plasma BDNF levels were measured using an enzyme-linked immunosorbent assay kit.Results: Forty-five (23.9% patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR criteria for a MDD. There were no significant effects of the 5-HTTLPR or BDNF Val66Met gene polymorphism on MDD among the hemodialysis patients. The plasma BDNF levels correlated significantly with age (P=0.003 and sex (P=0.047 but not with depression, the genotypes of 5

  17. Electrical and electrothermal transport in InN: The roles of defects

    International Nuclear Information System (INIS)

    The transport properties of Mg doped and undoped InN films are studied with capacitance-voltage, thermopower, and Hall mobility measurements. A positive Seebeck coefficient is observed for Mg doped InN confirming p-type conductivity, though high doping and structural defect density can lead to n-type films. Transport measurements of undoped films are analyzed employing Rode's iterative Boltzmann equation method. Observed thermopower, Hall mobility, and dislocation density data for undoped films are consistent with calculations including the effects of charged line defect (donor-type dislocation) scattering.

  18. The impact of defect scattering on the quasi-ballistic transport of nanoscale conductors

    International Nuclear Information System (INIS)

    Using the Landauer approach for carrier transport, we analyze the impact of defects induced by ion irradiation on the transport properties of nanoscale conductors that operate in the quasi-ballistic regime. Degradation of conductance results from a reduction of carrier mean free path due to the introduction of defects in the conducting channel. We incorporate scattering mechanisms from radiation-induced defects into calculations of the transmission coefficient and present a technique for extracting modeling parameters from near-equilibrium transport measurements. These parameters are used to describe degradation in the transport properties of nanoscale devices using a formalism that is valid under quasi-ballistic operation. The analysis includes the effects of bandstructure and dimensionality on the impact of defect scattering and discusses transport properties of nanoscale devices from the diffusive to the ballistic limit. We compare calculations with recently published measurements of irradiated nanoscale devices such as single-walled carbon nanotubes, graphene, and deep-submicron Si metal-oxide-semiconductor field-effect transistors

  19. Defect chemistry and electronic transport in low-κ dielectrics studied with electrically detected magnetic resonance

    Science.gov (United States)

    Mutch, Michael J.; Lenahan, Patrick M.; King, Sean W.

    2016-03-01

    Defect mediated electronic transport phenomena in low-κ dielectric films are of great technological interest for state-of-the-art and next generation microprocessors. At the present time, the leading low-κ interlayer dielectrics and etch-stop layers are based upon a-SiOC:H and a-SiCN:H, respectively. In this study, we utilize electrically detected magnetic resonance (EDMR), a derivative of electron paramagnetic resonance, to provide physical insight into electronic transport, as well as the nature and origin of defects in dense and porous a-SiOC:H and dense a-SiCN:H films. Resonance measurements are performed before and after the removal of sacrificial porogens via UV treatments to understand the role of specific defect centers in electronic transport in a-SiOC:H systems, and the nature of defects created by UV treatments. Unfortunately, a-SiOC:H and a-SiCN:H EDMR spectra are relatively broad and featureless. These featureless spectra are consistent with fairly complex a-SiOC:H and a-SiCN:H systems. We argue that physical insight may be gleaned from featureless spectra via multiple frequency EDMR. Baseline multiple frequency EDMR measurements are performed in a-Si:H and a-C:H to illustrate the nature of line broadening mechanisms of silicon and carbon related defects.

  20. Asymmetric energy transport in defected boron nitride nanoribbons: Implications for thermal rectification

    Directory of Open Access Journals (Sweden)

    Krishna Muralidharan

    2011-12-01

    Full Text Available Using molecular dynamics simulations, the thermal transport properties of boron nitride nanoribbons (BNNR containing geometrically-asymmetric triangular nano-vacancies were investigated. By suitably interpreting the time-evolution of spatially decomposed heat-current autocorrelation function in terms of phonon propagation characteristics, we have demonstrated the possibility of observing defect induced direction-dependent thermal transport in BNNR. This was further confirmed by appropriate analysis of direction dependent thermal diffusivity estimations in BNNR.

  1. HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology.

    Science.gov (United States)

    Gaub, Perrine; de Léon, Andrès; Gibon, Julien; Soubannier, Vincent; Dorval, Geneviève; Séguéla, Philippe; Barker, Philip A

    2016-01-01

    Neurotrophins activate intracellular signaling pathways necessary for neuronal survival, growth and apoptosis. The most abundant neurotrophin in the adult brain, brain-derived neurotrophic factor (BDNF), is first synthesized as a proBDNF precursor and recent studies have demonstrated that proBDNF can be secreted and that it functions as a ligand for a receptor complex containing p75NTR and sortilin. Activation of proBDNF receptors mediates growth cone collapse, reduces synaptic activity, and facilitates developmental apoptosis of motoneurons but the precise signaling cascades have been difficult to discern. To address this, we have engineered, expressed and purified HBpF-proBDNF, an expression construct containing a 6X-HIS tag, a biotin acceptor peptide (BAP) sequence, a PreScission™ Protease cleavage site and a FLAG-tag attached to the N-terminal part of murine proBDNF. Intact HBpF-proBDNF has activities indistinguishable from its wild-type counterpart and can be used to purify proBDNF signaling complexes or to monitor proBDNF endocytosis and retrograde transport. HBpF-proBDNF will be useful for characterizing proBDNF signaling complexes and for deciphering the role of proBDNF in neuronal development, synapse function and neurodegenerative disease. PMID:26950209

  2. Strong Coupling between Nanofluidic Transport and Interfacial Chemistry: How Defect Reactivity Controls Liquid-Solid Friction through Hydrogen Bonding.

    Science.gov (United States)

    Joly, Laurent; Tocci, Gabriele; Merabia, Samy; Michaelides, Angelos

    2016-04-01

    Defects are inevitably present in nanofluidic systems, yet the role they play in nanofluidic transport remains poorly understood. Here, we report ab initio molecular dynamics (AIMD) simulations of the friction of liquid water on defective graphene and boron nitride sheets. We show that water dissociates at certain defects and that these "reactive" defects lead to much larger friction than the "nonreactive" defects at which water molecules remain intact. Furthermore, we find that friction is extremely sensitive to the chemical structure of reactive defects and to the number of hydrogen bonds they can partake in with the liquid. Finally, we discuss how the insight obtained from AIMD can be used to quantify the influence of defects on friction in nanofluidic devices for water treatment and sustainable energy harvesting. Overall, we provide new insight into the role of interfacial chemistry on nanofluidic transport in real, defective systems. PMID:27012818

  3. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A;

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been no...... studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

  4. Regulation of BDNF Expression by Cocaine

    OpenAIRE

    McCarthy, Deirdre M.; Brown, Amber N.; Bhide, Pradeep G.

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. It is expressed throughout the nervous system. A unique feature of the BDNF gene is the existence of multiple mRNA transcripts, all of which are translated into BDNF protein, suggesting a multilevel regulation of expression. In particular, the BDNF exon IV promoter region is a preferential target for epigenetic alterations, as it contains binding sites for CREB and MeCP2, two transcriptional reg...

  5. Evaluation of defects in RE123 superconductors from magnetic field mapping by transport current

    International Nuclear Information System (INIS)

    The magnetic field distributions caused by a transport current were evaluated for the detection of defects in a bulk conductor especially grain boundaries. In the magnetic field mapping of single domain samples, the strength of a magnetic field was constant along the current direction while it changed in the samples having grain boundaries which limited the transport current. This means that the existence of grain boundaries could be detected from the magnetic field mapping pattern induced by the transport current. In addition, the difference of Jc in the width direction could also be identified from the magnetic field mapping in the single domain sample

  6. Electronic transport properties in random one-dimensional chains containing mesoscopic-ring defects

    Science.gov (United States)

    Huang, X.

    1999-11-01

    We study the electronic transport properties in one-dimensional systems with two kinds of mesoscopic ring defects: squarelike mesoscopic ring (SMR) defects and siamese-twins-like mescoscopic ring (STMR) defects. By using the transfer-matrix method, the resonant energies (where the transmission coefficient T=1) are derived successfully for both system. For the one SMR defect system, two resonant energies are found as a function of the magnetic flux Φ threading the ring defect, while for the latter case, two magnetic-flux-dependent and one magnetic-flux-independent resonant energies are predicted in the system, furthermore, if Φ takes some specific values, one of the Φ-dependent resonant energies may be the same as the Φ-independent resonant energy. The word ``resonant'' is used to describe this situation. When a finite concentration of SMR or STMR defects are randomly embedded in a perfect chain, the numerical results confirm all the analytical predictions. Finally, for the ``resonant'' case, we show numerically a rather wide perfect transmission region which is almost ten times as wide as that of the ``unresonant'' case.

  7. Defect and transport properties of nanocrystalline CeO2-x

    International Nuclear Information System (INIS)

    It is shown that unique defect thermodynamics and transport properties result for oxides of a few nanometers crystallite size. Fully-dense CeO2-x polycrystals of ∼10 nm grain size were synthesized, and their electrical properties compared with those of samples coarsened from the same material. The nanocrystals showed reduced grain boundary resistance, 104 higher electronic conductivity, and less than one-half the heat of reduction of its coarse-grained counterpart. These properties are attributed to a dominant role of interfacial defect formation. copyright 1996 American Institute of Physics

  8. SorCS2 is required for BDNF-dependent plasticity in the hippocampus

    DEFF Research Database (Denmark)

    Glerup, S; Bolcho, U; Bøggild, S;

    2016-01-01

    that hippocampal N-methyl-d-aspartate receptor-dependent synaptic plasticity is eliminated in SorCS2-deficient mice. This defect was traced to the ability of SorCS2 to form complexes with the neurotrophin receptor p75(NTR), required for pro-brain-derived neurotrophic factor (BDNF) to induce long...... potentiation. Neurons lacking SorCS2 failed to respond to BDNF by TrkB autophosphorylation, and activation of downstream signaling cascades, impacting neurite outgrowth and spine formation. Accordingly, Sorcs2(-/-) mice displayed impaired formation of long-term memory, increased risk taking and stimulus...... seeking behavior, enhanced susceptibility to stress and impaired prepulse inhibition. Our results identify SorCS2 as an indispensable coreceptor for p75(NTR) and TrkB in hippocampal neurons and suggest SORCS2 as the link between proBDNF/BDNF signaling and mental disorders.Molecular Psychiatry advance...

  9. Transport mechanisms of uranium released to the coolant from fuel defects

    International Nuclear Information System (INIS)

    Fuel performance at domestic CANDU-600s, Point Lepreau and Gentilly, has been very good, with only a small number of fuel defects releasing uranium to the coolant. The in-core monitoring on these early fuel defects using the delayed neutron system, provides some insight into uranium transport mechanisms and how they influence signal trends. Better understanding of these mechanisms, will assist the station operator in responding to trend changes and will ultimately provide guidance in assigning removal priorities should several fuel defects occur simultaneously. The average delayed neutron signal of all channels is the key parameter for monitoring fuel performance in-core, and should be regarded as an early warning indicator of fuel performance problems

  10. The defect effects on the signal transport of an excitable soft cable

    Science.gov (United States)

    Liu, Tang-Yu; Chang, Cheng-Hung

    2013-03-01

    How a local perturbation affects a propagating wave traveling in a homogeneous medium is a general physics question widely investigated in condensed materials. Intuitively, one might expect that a perturbation would suppress the transport ability of the medium if it is quasi one dimensional. This is generically true as defects and impurities influence numerous non-excitable systems such as carbon nanotubes, nanowires and DNA double helixes. However, if the system is excitable, such as a neuron, a defect may generate a highly non-trivial dynamical behavior. In this paper, using the Hodgkin-Huxley model, we explored this diversity generated by locally non-uniform ion channel densities caused by toxins, diseases, environmental disorders or artificial manipulations. These channel density defects could induce several exotic behaviors, in contrast with the normal destructive role of defects in solid-state physics. They may behave as an electric signal generator exhibiting spontaneous or stimulated emissions, as well as trap, reflect, rectify, delay or extinguish propagating signals or be switched to different functions by a signal. Nonlinear analysis and phase diagrams were used to quantify this dynamical complexity. The results may contribute to research on signal manipulation in biotechnology, neuronal diseases and damages, channel distribution-related cell functions and defect dynamics in general excitable mathematical models.

  11. Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester.

    OpenAIRE

    Jonas, A J; Butler, I J

    1989-01-01

    Tryptophan ethyl ester, a lipid-soluble tryptophan derivative, was used to bypass defective gastrointestinal neutral amino acid transport in a child with Hartnup disease. The child's baseline tryptophan concentrations in serum (20 +/- 6 microM) and cerebrospinal fluid (1.0 +/- 0.2 microM) were persistently less than 50% of normal values. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, was also less than 50% of normal (21 +/- 2 ng/ml). Serum tryptophan concentr...

  12. BDNF in sleep, insomnia, and sleep deprivation.

    Science.gov (United States)

    Schmitt, Karen; Holsboer-Trachsler, Edith; Eckert, Anne

    2016-01-01

    The protein brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors involved in plasticity of neurons in several brain regions. There are numerous evidence that BDNF expression is decreased by experiencing psychological stress and that, accordingly, a lack of neurotrophic support causes major depression. Furthermore, disruption in sleep homeostatic processes results in higher stress vulnerability and is often associated with stress-related mental disorders. Recently, we reported, for the first time, a relationship between BDNF and insomnia and sleep deprivation (SD). Using a biphasic stress model as explanation approach, we discuss here the hypothesis that chronic stress might induce a deregulation of the hypothalamic-pituitary-adrenal system. In the long-term it leads to sleep disturbance and depression as well as decreased BDNF levels, whereas acute stress like SD can be used as therapeutic intervention in some insomniac or depressed patients as compensatory process to normalize BDNF levels. Indeed, partial SD (PSD) induced a fast increase in BDNF serum levels within hours after PSD which is similar to effects seen after ketamine infusion, another fast-acting antidepressant intervention, while traditional antidepressants are characterized by a major delay until treatment response as well as delayed BDNF level increase. Key messages Brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of stress-related mood disorders. The interplay of stress and sleep impacts on BDNF level. Partial sleep deprivation (PSD) shows a fast action on BDNF level increase. PMID:26758201

  13. Defect chemistry and transport properties of BaxCe0.85M0.15O3-d

    OpenAIRE

    Wu, J.; Li, L. P.; Espinosa, W. T. P.; Haile, S. M.

    2004-01-01

    The site-incorporation mechanism of M3+ dopants into A2+B4+O3 perovskites controls the overall defect chemistry and thus their transport properties. For charge-balance reasons, incorporation onto the A2+-site would require the creation of negatively charged point defects (such as cation vacancies), whereas incorporation onto the B4+-site is accompanied by the generation of positively charged defects, typically oxygen vacancies. Oxygen-vacancy content, in turn, is relevant to proton-conducting...

  14. Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester.

    Science.gov (United States)

    Jonas, A J; Butler, I J

    1989-07-01

    Tryptophan ethyl ester, a lipid-soluble tryptophan derivative, was used to bypass defective gastrointestinal neutral amino acid transport in a child with Hartnup disease. The child's baseline tryptophan concentrations in serum (20 +/- 6 microM) and cerebrospinal fluid (1.0 +/- 0.2 microM) were persistently less than 50% of normal values. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, was also less than 50% of normal (21 +/- 2 ng/ml). Serum tryptophan concentrations increased only modestly and briefly after an oral challenge with 200 mg/kg of oral L-tryptophan, reflecting the absorptive defect. An oral challenge with 200 mg/kg of tryptophan ethyl ester resulted in a prompt increase in serum tryptophan to a peak of 555 microM. Sustained treatment with 20 mg/kg q6h resulted in normalization of serum (66 +/- 15 microM) and cerebrospinal fluid tryptophan concentrations (mean = 2.3 microM). Cerebrospinal fluid 5-HIAA increased to more normal concentrations (mean = 33 ng/ml). No toxicity was observed over an 8-mo period of treatment, chronic diarrhea resolved, and body weight, which had remained unchanged for 7 mo before ester therapy, increased by approximately 26%. We concluded that tryptophan ethyl ester is effective at circumventing defective gastrointestinal neutral amino acid transport and may be useful in the treatment of Hartnup disease. PMID:2472426

  15. Regulation of BDNF expression by cocaine.

    Science.gov (United States)

    McCarthy, Deirdre M; Brown, Amber N; Bhide, Pradeep G

    2012-12-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. It is expressed throughout the nervous system. A unique feature of the BDNF gene is the existence of multiple mRNA transcripts, all of which are translated into BDNF protein, suggesting a multilevel regulation of expression. In particular, the BDNF exon IV promoter region is a preferential target for epigenetic alterations, as it contains binding sites for CREB and MeCP2, two transcriptional regulators known to mediate epigenetic changes. Exposure to drugs of abuse is known to modulate epigenetic regulation of BDNF gene expression. This review will discuss how exposure to cocaine, one of the most addictive drugs known to mankind, can produce alterations in BDNF gene expression, especially in the mesolimbic dopaminergic system, which lead to alterations in the reward-mediated behaviors involved in addiction. PMID:23239946

  16. Width and defect effects on the electronic transport of zigzag MoS2 nanoribbons

    Science.gov (United States)

    An, Yipeng; Zhang, Mengjun; Da, Haixia; Fu, Zhaoming; Jiao, Zhaoyong; Liu, Zhiyong

    2016-06-01

    Using first-principles methods, we investigate the electronic transport properties of zigzag MoS2 nanoribbons (Z-MoS2NRs). The current–voltage (I–V) curves of Z-MoS2NRs show a negative differential resistive (NDR) effect, and are independent of nanoribbon width. The current flowing through the nanoribbon is mainly along the Mo-edge, with two different local current channels (Mo  →  Mo hop current and S  →  Mo  →  S bond current). The current will be suppressed when introducing a Mo vacancy-defect at the Mo-edge under low biases—while, under high biases, the current through the defected Z-MoS2NRs will increase a little, due to the other S-edge channel being opened.

  17. Electronic transport through a ladder nano structure in the presence of network defects

    International Nuclear Information System (INIS)

    The present research studied the electronic transport of an ideal infinite ladder nano structure in the presence/absence of network defects by using Green's function method at the tight-binding approximation. The network defects can be simulated by considering a finite ladder which is connected via two contacts to two similar infinite ladders. The results showed that the hopping energy of rungs determines the overlapping region of the ladder conductance channels. By increasing hopping energy of rungs, the allowed energy region of the ladder increases, while the overlapping region shrinks and eventually vanishes. Creation of branched bonds in the center ladder leads, through the system, to a harder electron tunneling. Moreover, the closer electron energy to the system gap edges leads to a better tunneling.

  18. Multiple faces of BDNF in cocaine addiction

    OpenAIRE

    Li, Xuan; Wolf, Marina E.

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) has been found to play roles in many types of plasticity including drug addiction. Here we focus on rodent studies over the past two decades that have demonstrated diverse roles of BDNF in models of cocaine addiction. First, we will provide an overview of studies showing that cocaine exposure alters (and generally increases) BDNF levels in reward-related regions including the ventral tegmental area, nucleus accumbens, prefrontal cortex, and amygdala. T...

  19. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A;

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been ...

  20. Multiple faces of BDNF in cocaine addiction.

    Science.gov (United States)

    Li, Xuan; Wolf, Marina E

    2015-02-15

    Brain-derived neurotrophic factor (BDNF) has been found to play roles in many types of plasticity including drug addiction. Here, we focus on rodent studies over the past two decades that have demonstrated diverse roles of BDNF in models of cocaine addiction. First, we will provide an overview of studies showing that cocaine exposure alters (and generally increases) BDNF levels in reward-related regions including the ventral tegmental area, nucleus accumbens, prefrontal cortex, and amygdala. Then we will review evidence that BDNF contributes to behavioral changes in animal models of cocaine addiction, focusing on conditioned place preference, behavioral sensitization, maintenance and reinstatement of self-administration, and incubation of cocaine craving. Last, we will review the role of BDNF in synaptic plasticity, particularly as it relates to plasticity of AMPA receptor transmission after cocaine exposure. We conclude that BDNF regulates cocaine-induced behaviors in a highly complex manner that varies depending on the brain region (and even among different cell types within the same brain region), the nature of cocaine exposure, and the "addiction phase" examined (e.g., acquisition vs maintenance; early vs late withdrawal). These complexities make BDNF a daunting therapeutic target for treating cocaine addiction. However, recent clinical evidence suggests that the serum BDNF level may serve as a biomarker in cocaine addicts to predict future relapse, providing an alternative direction for exploring BDNF's potential relevance to treating cocaine addiction. PMID:25449839

  1. Neuroticism, depressive symptoms, and serum BDNF

    Science.gov (United States)

    Terracciano, Antonio; Lobina, Monia; Piras, Maria Grazia; Mulas, Antonella; Cannas, Alessandra; Meirelles, Osorio; Sutin, Angelina R.; Zonderman, Alan B; Uda, Manuela; Crisponi, Laura; Schlessinger, David

    2011-01-01

    Objective Animal models and clinical studies suggest that brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of depression. We test whether serum and plasma levels of BDNF are associated with trait Neuroticism and its facets, and with state measure of depressive symptoms. Method In a community-based cohort (N = 2099) we measured serum and plasma BDNF concentration, administered the Revised NEO Personality Inventory (NEO-PI-R) and the Center for Epidemiologic Studies Depression Scale (CES-D). Covariates included age, sex, cigarette smoking, obesity, and antidepressant use. Results Serum BDNF concentrations were inversely related to Neuroticism (r = −0.074, P < 0.001), in particular the Depression facet (r = −0.08, P < 0.001). Lower BDNF concentrations were also associated with severe depressive symptoms (CES-D ≥ 28; OR = 0.906; 95%CI = 0.851–0.965). The association of serum BDNF with Neuroticism was independent of depressive symptoms, indicating that serum BDNF might represent a biological correlate of Neuroticism and not just of transient depressive states. Plasma BDNF was not associated with measures of depression. Conclusions Our study suggests that lower serum BDNF is associated with both a dispositional vulnerability to depression and acute depressive states in the general population. PMID:21949427

  2. Charge transport model in solid-state avalanche amorphous selenium and defect suppression design

    Science.gov (United States)

    Scheuermann, James R.; Miranda, Yesenia; Liu, Hongyu; Zhao, Wei

    2016-01-01

    Avalanche amorphous selenium (a-Se) in a layer of High Gain Avalanche Rushing Photoconductor (HARP) is being investigated for its use in large area medical imagers. Avalanche multiplication of photogenerated charge requires electric fields greater than 70 V μm-1. For a-Se to withstand this high electric field, blocking layers are used to prevent the injection of charge carriers from the electrodes. Blocking layers must have a high injection barrier and deep trapping states to reduce the electric field at the interface. In the presence of a defect in the blocking layer, a distributed resistive layer (DRL) must be included into the structure to build up space charge and reduce the electric field in a-Se and the defect. A numerical charge transport model has been developed to optimize the properties of blocking layers used in various HARP structures. The model shows the incorporation of a DRL functionality into the p-layer can reduce dark current at a point defect by two orders of magnitude by reducing the field in a-Se to the avalanche threshold. Hole mobility in a DRL of ˜10-8 cm2 V-1 s-1 at 100 V μm-1 as demonstrated by the model can be achieved experimentally by varying the hole mobility of p-type organic or inorganic semiconductors through doping, e.g., using Poly(9-vinylcarbozole) doped with 1%-3% (by weight) of poly(3-hexylthiopene).

  3. Thermal transport in UO2 with defects and fission products by molecular dynamics simulations

    International Nuclear Information System (INIS)

    The importance of the thermal transport in nuclear fuel has motivated a wide range of experimental and modelling studies. In this report, the reduction of thermal transport in UO2 due to defects and fission products has been investigated using non-equilibrium MD simulations, with two sets of empirical potentials for studying the degregation of UO2 thermal conductivity including a Buckingham type interatomic potential and a recently developed EAM type interatomic potential. Additional parameters for U5+ and Zr4+ in UO2 have been developed for the EAM potential. The thermal conductivity results from MD simulations are then corrected for the spin-phonon scattering through Callaway model formulations. To validate the modelling results, comparison was made with experimental measurements on single crystal hyper-stoichiometric UO2+x samples.

  4. Effects of line defects on spin-dependent electronic transport of zigzag MoS2 nanoribbons

    International Nuclear Information System (INIS)

    The nonlinear spin-dependent transport properties in zigzag molybdenum-disulfide nanoribbons (ZMNRs) with line defects are investigated systematically using nonequilibrium Green’s function method combined with density functional theory. The results show that the line defects can enhance the electronic transfer ability of ZMNRs. The types and locations of the line defects are found critical in determining the spin polarization and the current-voltage (I-V) characteristics of the line defected ZMNRs. For the same defect type, the total currents of the ribbons with the line defects in the centers are lager than those on the edges. And for the same location, the total currents of the systems with the sulfur (S) line defect are larger than the according systems with the molybdenum (Mo) line defect. All the considered systems present magnetism properties. And in the S line defected systems, the spin reversal behaviors can be observed. In both the spin-up and spin-down states of the Mo line defected systems, there are obvious negative differential resistance behaviors. The mechanisms are proposed for these phenomena

  5. Effects of line defects on spin-dependent electronic transport of zigzag MoS{sub 2} nanoribbons

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xin-Mei; Yang, Kai-Wei; Zhang, Dan; Ding, Jia-Feng; Xu, Hui, E-mail: xuhui@csu.edu.cn [Institute of Super-microstructure and Ultrafast Process in Advanced Materials & Hunan Key Laboratory for Super-microstructure and Ultrafast Process, School of Physics and Electronics, Central South University, Changsha 410083 (China); Long, Meng-Qiu, E-mail: mqlong@csu.edu.cn [Institute of Super-microstructure and Ultrafast Process in Advanced Materials & Hunan Key Laboratory for Super-microstructure and Ultrafast Process, School of Physics and Electronics, Central South University, Changsha 410083 (China); Department of Physics and Materials Science, City University of Hong Kong, Hong Kong (China); Cui, Li-Ling [Institute of Super-microstructure and Ultrafast Process in Advanced Materials & Hunan Key Laboratory for Super-microstructure and Ultrafast Process, School of Physics and Electronics, Central South University, Changsha 410083 (China); School of Science, Hunan University of Technology, Zhuzhou 412007 (China)

    2016-01-15

    The nonlinear spin-dependent transport properties in zigzag molybdenum-disulfide nanoribbons (ZMNRs) with line defects are investigated systematically using nonequilibrium Green’s function method combined with density functional theory. The results show that the line defects can enhance the electronic transfer ability of ZMNRs. The types and locations of the line defects are found critical in determining the spin polarization and the current-voltage (I-V) characteristics of the line defected ZMNRs. For the same defect type, the total currents of the ribbons with the line defects in the centers are lager than those on the edges. And for the same location, the total currents of the systems with the sulfur (S) line defect are larger than the according systems with the molybdenum (Mo) line defect. All the considered systems present magnetism properties. And in the S line defected systems, the spin reversal behaviors can be observed. In both the spin-up and spin-down states of the Mo line defected systems, there are obvious negative differential resistance behaviors. The mechanisms are proposed for these phenomena.

  6. Effects of line defects on spin-dependent electronic transport of zigzag MoS2 nanoribbons

    Directory of Open Access Journals (Sweden)

    Xin-Mei Li

    2016-01-01

    Full Text Available The nonlinear spin-dependent transport properties in zigzag molybdenum-disulfide nanoribbons (ZMNRs with line defects are investigated systematically using nonequilibrium Green’s function method combined with density functional theory. The results show that the line defects can enhance the electronic transfer ability of ZMNRs. The types and locations of the line defects are found critical in determining the spin polarization and the current-voltage (I-V characteristics of the line defected ZMNRs. For the same defect type, the total currents of the ribbons with the line defects in the centers are lager than those on the edges. And for the same location, the total currents of the systems with the sulfur (S line defect are larger than the according systems with the molybdenum (Mo line defect. All the considered systems present magnetism properties. And in the S line defected systems, the spin reversal behaviors can be observed. In both the spin-up and spin-down states of the Mo line defected systems, there are obvious negative differential resistance behaviors. The mechanisms are proposed for these phenomena.

  7. Pathogenic mutations causing glucose transport defects in GLUT1 transporter: The role of intermolecular forces in protein structure-function.

    Science.gov (United States)

    Raja, Mobeen; Kinne, Rolf K H

    2015-01-01

    Two families of glucose transporter - the Na(+)-dependent glucose cotransporter-1 (SGLT family) and the facilitated diffusion glucose transporter family (GLUT family) - play a crucial role in the translocation of glucose across the epithelial cell membrane. How genetic mutations cause life-threatening diseases like GLUT1-deficiency syndrome (GLUT1-DS) is not well understood. In this review, we have combined previous functional data with our in silico analyses of the bacterial homologue of GLUT members, XylE (an outward-facing, partly occluded conformation) and previously proposed GLUT1 homology model (an inward-facing conformation). A variety of native and mutant side chain interactions were modeled to highlight the potential roles of mutations in destabilizing protein-protein interaction hence triggering structural and functional defects. This study sets the stage for future studies of the structural properties that mediate GLUT1 dysfunction and further suggests that both SGLT and GLUT families share conserved domains that stabilize the transporter structure/function via a similar mechanism. PMID:25863194

  8. Multiple faces of BDNF in cocaine addiction

    Science.gov (United States)

    Li, Xuan; Wolf, Marina E.

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) has been found to play roles in many types of plasticity including drug addiction. Here we focus on rodent studies over the past two decades that have demonstrated diverse roles of BDNF in models of cocaine addiction. First, we will provide an overview of studies showing that cocaine exposure alters (and generally increases) BDNF levels in reward-related regions including the ventral tegmental area, nucleus accumbens, prefrontal cortex, and amygdala. Then we will review evidence that BDNF contributes to behavioral changes in animal models of cocaine addiction, focusing on conditioned place preference, behavioral sensitization, maintenance and reinstatement of self-administration, and incubation of cocaine craving. Last, we will review the role of BDNF in synaptic plasticity, particularly as it relates to plasticity of AMPA receptor transmission after cocaine exposure. We conclude that BDNF regulates cocaine-induced behaviors in a highly complex manner that varies depending on the brain region (and even among different cell types within the same brain region), the nature of cocaine exposure, and the “addiction phase” examined (e.g., acquisition vs maintenance; early vs late withdrawal). These complexities make BDNF a daunting therapeutic target for treating cocaine addiction. However, recent clinical evidence suggests that the serum BDNF level may serve as a biomarker in cocaine addicts to predict future relapse, providing an alternative direction for exploring BDNF’s potential relevance to treating cocaine addiction. PMID:25449839

  9. ARCN1 Mutations Cause a Recognizable Craniofacial Syndrome Due to COPI-Mediated Transport Defects.

    Science.gov (United States)

    Izumi, Kosuke; Brett, Maggie; Nishi, Eriko; Drunat, Séverine; Tan, Ee-Shien; Fujiki, Katsunori; Lebon, Sophie; Cham, Breana; Masuda, Koji; Arakawa, Michiko; Jacquinet, Adeline; Yamazumi, Yusuke; Chen, Shu-Ting; Verloes, Alain; Okada, Yuki; Katou, Yuki; Nakamura, Tomohiko; Akiyama, Tetsu; Gressens, Pierre; Foo, Roger; Passemard, Sandrine; Tan, Ene-Choo; El Ghouzzi, Vincent; Shirahige, Katsuhiko

    2016-08-01

    Cellular homeostasis is maintained by the highly organized cooperation of intracellular trafficking systems, including COPI, COPII, and clathrin complexes. COPI is a coatomer protein complex responsible for intracellular protein transport between the endoplasmic reticulum and the Golgi apparatus. The importance of such intracellular transport mechanisms is underscored by the various disorders, including skeletal disorders such as cranio-lenticulo-sutural dysplasia and osteogenesis imperfect, caused by mutations in the COPII coatomer complex. In this article, we report a clinically recognizable craniofacial disorder characterized by facial dysmorphisms, severe micrognathia, rhizomelic shortening, microcephalic dwarfism, and mild developmental delay due to loss-of-function heterozygous mutations in ARCN1, which encodes the coatomer subunit delta of COPI. ARCN1 mutant cell lines were revealed to have endoplasmic reticulum stress, suggesting the involvement of ER stress response in the pathogenesis of this disorder. Given that ARCN1 deficiency causes defective type I collagen transport, reduction of collagen secretion represents the likely mechanism underlying the skeletal phenotype that characterizes this condition. Our findings demonstrate the importance of COPI-mediated transport in human development, including skeletogenesis and brain growth. PMID:27476655

  10. BDNF signaling and survival of striatal neurons

    Directory of Open Access Journals (Sweden)

    Baoji Xu

    2014-08-01

    Full Text Available The striatum, a major component of the basal ganglia, performs multiple functions including control of movement, reward, and addiction. Dysfunction and death of striatal neurons are the main causes for the motor disorders associated with Huntington’s disease (HD. Brain-derived neurotrophic factor (BDNF, a member of the neurotrophin family, is among factors that promote survival and proper function of this neuronal population. Here, we review recent studies showing that BDNF determines the size of the striatum by supporting survival of the immature striatal neurons at their origin, promotes maturation of striatal neurons, and facilitates establishment of striatal connections during brain development. We also examine the role of BDNF in maintaining proper function of the striatum during adulthood, summarize the mechanisms that lead to a deficiency in BDNF signaling and subsequently striatal degeneration in HD, and highlight a potential role of BDNF as a therapeutic target for HD treatment.

  11. Band-like transport in highly crystalline graphene films from defective graphene oxides

    Science.gov (United States)

    Negishi, R.; Akabori, M.; Ito, T.; Watanabe, Y.; Kobayashi, Y.

    2016-01-01

    The electrical transport property of the reduced graphene oxide (rGO) thin-films synthesized from defective GO through thermal treatment in a reactive ethanol environment at high temperature above 1000 °C shows a band-like transport with small thermal activation energy (Ea~10 meV) that occurs during high carrier mobility (~210 cm2/Vs). Electrical and structural analysis using X-ray absorption fine structure, the valence band photo-electron, Raman spectra and transmission electron microscopy indicate that a high temperature process above 1000 °C in the ethanol environment leads to an extraordinary expansion of the conjugated π-electron system in rGO due to the efficient restoration of the graphitic structure. We reveal that Ea decreases with the increasing density of states near the Fermi level due to the expansion of the conjugated π-electron system in the rGO. This means that Ea corresponds to the energy gap between the top of the valence band and the bottom of the conduction band. The origin of the band-like transport can be explained by the carriers, which are more easily excited into the conduction band due to the decreasing energy gap with the expansion of the conjugated π-electron system in the rGO. PMID:27364116

  12. Band-like transport in highly crystalline graphene films from defective graphene oxides

    Science.gov (United States)

    Negishi, R.; Akabori, M.; Ito, T.; Watanabe, Y.; Kobayashi, Y.

    2016-07-01

    The electrical transport property of the reduced graphene oxide (rGO) thin-films synthesized from defective GO through thermal treatment in a reactive ethanol environment at high temperature above 1000 °C shows a band-like transport with small thermal activation energy (Ea~10 meV) that occurs during high carrier mobility (~210 cm2/Vs). Electrical and structural analysis using X-ray absorption fine structure, the valence band photo-electron, Raman spectra and transmission electron microscopy indicate that a high temperature process above 1000 °C in the ethanol environment leads to an extraordinary expansion of the conjugated π-electron system in rGO due to the efficient restoration of the graphitic structure. We reveal that Ea decreases with the increasing density of states near the Fermi level due to the expansion of the conjugated π-electron system in the rGO. This means that Ea corresponds to the energy gap between the top of the valence band and the bottom of the conduction band. The origin of the band-like transport can be explained by the carriers, which are more easily excited into the conduction band due to the decreasing energy gap with the expansion of the conjugated π-electron system in the rGO.

  13. Peripheral vascular reactivity and serum BDNF responses to aerobic training are impaired by the BDNF Val66Met polymorphism.

    Science.gov (United States)

    Lemos, José R; Alves, Cleber R; de Souza, Sílvia B C; Marsiglia, Julia D C; Silva, Michelle S M; Pereira, Alexandre C; Teixeira, Antônio L; Vieira, Erica L M; Krieger, José E; Negrão, Carlos E; Alves, Guilherme B; de Oliveira, Edilamar M; Bolani, Wladimir; Dias, Rodrigo G; Trombetta, Ivani C

    2016-02-01

    Besides neuronal plasticity, the neurotrophin brain-derived neurotrophic factor (BDNF) is also important in vascular function. The BDNF has been associated with angiogenesis through its specific receptor tropomyosin-related kinase B (TrkB). Additionally, Val66Met polymorphism decreases activity-induced BDNF. Since BDNF and TrkB are expressed in vascular endothelial cells and aerobic exercise training can increase serum BDNF, this study aimed to test the hypotheses: 1) Serum BDNF levels modulate peripheral blood flow; 2) The Val66Met BDNF polymorphism impairs exercise training-induced vasodilation. We genotyped 304 healthy male volunteers (Val66Val, n = 221; Val66Met, n = 83) who underwent intense aerobic exercise training on a running track three times/wk for 4 mo. We evaluated pre- and post-exercise training serum BDNF and proBDNF concentration, heart rate (HR), mean blood pressure (MBP), forearm blood flow (FBF), and forearm vascular resistance (FVR). In the pre-exercise training, BDNF, proBDNF, BDNF/proBDNF ratio, FBF, and FVR were similar between genotypes. After exercise training, functional capacity (V̇o2 peak) increased and HR decreased similarly in both groups. Val66Val, but not Val66Met, increased BDNF (interaction, P = 0.04) and BDNF/proBDNF ratio (interaction, P < 0.001). Interestingly, FBF (interaction, P = 0.04) and the FVR (interaction, P = 0.01) responses during handgrip exercise (HG) improved in Val66Val compared with Val66Met, even with similar responses of HR and MBP. There were association between BDNF/proBDNF ratio and FBF (r = 0.64, P < 0.001) and FVR (r = -0.58, P < 0.001) during HG exercise. These results show that peripheral vascular reactivity and serum BDNF responses to exercise training are impaired by the BDNF Val66Met polymorphism and such responsiveness is associated with serum BDNF concentrations in healthy subjects. PMID:26603150

  14. The metabolic basis for developmental disorders due to defective folate transport.

    Science.gov (United States)

    Desai, Ankuri; Sequeira, Jeffrey M; Quadros, Edward V

    2016-07-01

    Folates are essential in the intermediary metabolism of amino acids, synthesis of nucleotides and for maintaining methylation reactions. They are also linked to the production of neurotransmitters through GTP needed for the synthesis of tetrahydrobiopterin. During pregnancy, folate is needed for fetal development. Folate deficiency during this period has been linked to increased risk of neural tube defects. Disturbances of folate metabolism due to genetic abnormalities or the presence of autoantibodies to folate receptor alpha (FRα) can impair physiologic processes dependent on folate, resulting in a variety of developmental disorders including cerebral folate deficiency syndrome and autism spectrum disorders. Overall, adequate folate status has proven to be important during pregnancy as well as neurological development and functioning in neonates and children. Treatment with pharmacologic doses of folinic acid has led to reversal of some symptoms in many children diagnosed with cerebral folate deficiency syndrome and autism, especially in those positive for autoantibodies to FRα. Thus, as the brain continues to develop throughout fetal and infant life, it can be affected and become dysfunctional due to a defective folate transport contributing to folate deficiency. Treatment and prevention of these disorders can be achieved by identification of those at risk and supplementation with folinic acid. PMID:26924398

  15. Proteolytic Cleavage of ProBDNF into Mature BDNF in the Basolateral Amygdala Is Necessary for Defeat-Induced Social Avoidance

    Science.gov (United States)

    Dulka, Brooke N.; Ford, Ellen C.; Lee, Melissa A.; Donnell, Nathaniel J.; Goode, Travis D.; Prosser, Rebecca; Cooper, Matthew A.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is essential for memory processes. The present study tested whether proteolytic cleavage of proBDNF into mature BDNF (mBDNF) within the basolateral amygdala (BLA) regulates the consolidation of defeat-related memories. We found that acute social defeat increases the expression of mBDNF, but not proBDNF, in…

  16. Transport limits in defect-engineered LaAlO3/SrTiO3 bilayers.

    Science.gov (United States)

    Gunkel, Felix; Wicklein, Sebastian; Hoffmann-Eifert, Susanne; Meuffels, Paul; Brinks, Peter; Huijben, Mark; Rijnders, Guus; Waser, Rainer; Dittmann, Regina

    2015-01-21

    The electrical properties of the metallic interface in LaAlO3/SrTiO3 (LAO/STO) bilayers are investigated with focus on the role of cationic defects in thin film STO. Systematic growth-control of the STO thin film cation stoichiometry (defect-engineering) yields a relation between cationic defects in the STO layer and electronic properties of the bilayer-interface. Hall measurements reveal a stoichiometry-effect primarily on the electron mobility. The results indicate an enhancement of scattering processes in as-grown non-stoichiometric samples indicating an increased density of defects. Furthermore, we discuss the thermodynamic processes and defect-exchange reactions at the LAO/STO-bilayer interface determined in high temperature equilibrium. By quenching defined defect states from high temperature equilibrium, we finally connect equilibrium thermodynamics with room temperature transport. The results are consistent with the defect-chemistry model suggested for LAO/STO interfaces. Moreover, they reveal an additional healing process of extended defects in thin film STO. PMID:25469599

  17. Constructing recombinant replication-defective adenoviral vectors that express glucose transporter-1 through in vitro ligation

    Institute of Scientific and Technical Information of China (English)

    Fangcheng Li; Junliang Li; Ranyi Liu; Xinke Xu; Kaichang Yuan; Zhonghua Wu

    2008-01-01

    BACKGROUND: We constructed a homologous recombination bacterial method based on the pAdEasy system, a widely used system, for generating recombinant adenoviral vectors that express glucose transporter-1 (GLUT1) in rats.OBJECTIVE: This study was designed to investigate the feasibility of generating recombinant replication-defective adenoviral vectors that express GLUT1 in rats by in vitro ligation based on the Adeno-XTM system. DESIGN: An in vitro cell-based experiment. SETTING: This study was performed at the Linbaixin Medical Research Center of the Second Hospital Affiliated to Sun Yat-sen University and Central Laboratory for Prevention and Treatment of Tumor, Sun Yat-sen University between January and August 2004. MATERIALS: Male, adult, Sprague Dawley rats were used to extract total RNA from brain tissue. E. coli DH5?and human embryonic kidney 293 cells (HEK293 cells) used in the present study were cryo-preserved by the Second Hospital Affiliated to Sun Yat-sen University. Rabbit anti-rat GLUT1 polyclonal antibody (Chemicon, U.S.A.) and primers (Shanghai Boya Bioengineering Co., Ltd) were also used. METHODS: E1/E3-deleted replication-defective adenoviral vectors were used. Using in vitro ligation, the target gene was first sub-cloned into a shuttle vector plasmid to obtain the fragment containing target gene expression cassettes by enzyme digestion. Subsequently, the fragment was co-transformed with linearized adenoviral backbone vector into the E. coli strain. The recombinant adenoviral plasmid was transfected into HEK293 cells to assembly recombinant adenoviral vectors with replication capabilities. The procedure was repeated several times for recombinant adenoviral vectors amplification. MAIN OUTCOME MEASURES: Efficiency of recombinant adenoviral vectors to express the target gene was measured by gene and protein expression through polymerase chain reaction and Western Blot assays, respectively.RESULTS: Results demonstrated that recombinant adenoviral

  18. BDNF and Huntingtin protein modifications by Manganese: Implications for striatal medium spiny neuron pathology in manganese neurotoxicity

    OpenAIRE

    Stansfield, Kirstie H.; Bichell, Terry Jo; Bowman, Aaron B.; Guilarte, Tomás R.

    2014-01-01

    High levels of manganese (Mn) exposure decreases striatal medium spiny neuron (MSN) dendritic length and spine density, but the mechanism(s) are not known. The Huntingtin (HTT) gene has been functionally linked to cortical brain-derived neurotrophic factor (BDNF) support of striatal MSNs via phosphorylation at serine 421 (S421). In Huntington's disease, pathogenic CAG-repeat expansions of HTT decrease synthesis and disrupt transport of cortical-striatal BDNF contributing to disease, and Mn is...

  19. BDNF and Huntingtin protein modifications by manganese: implications for striatal medium spiny neuron pathology in manganese neurotoxicity.

    Science.gov (United States)

    Stansfield, Kirstie H; Bichell, Terry Jo; Bowman, Aaron B; Guilarte, Tomás R

    2014-12-01

    High levels of manganese (Mn) exposure decrease striatal medium spiny neuron (MSN) dendritic length and spine density, but the mechanism(s) are not known. The Huntingtin (HTT) gene has been functionally linked to cortical brain-derived neurotrophic factor (BDNF) support of striatal MSNs via phosphorylation at serine 421. In Huntington's disease, pathogenic CAG repeat expansions of HTT decrease synthesis and disrupt transport of cortical-striatal BDNF, which may contribute to disease, and Mn is a putative environmental modifier of Huntington's disease pathology. Thus, we tested the hypothesis that changes in MSN dendritic morphology Mn due to exposure are associated with decreased BDNF levels and alterations in Htt protein. We report that BDNF levels are decreased in the striatum of Mn-exposed non-human primates and in the cerebral cortex and striatum of mice exposed to Mn. Furthermore, proBDNF and mature BDNF concentrations in primary cortical and hippocampal neuron cultures were decreased by exposure to Mn confirming the in vivo findings. Mn exposure decreased serine 421 phosphorylation of Htt in cortical and hippocampal neurons and increased total Htt levels. These data strongly support the hypothesis that Mn-exposure-related MSN pathology is associated with decreased BDNF trophic support via alterations in Htt. PMID:25099302

  20. An analytical solution to contaminant transport through composite liners with geomembrane defects

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    To investigate the performance of landfill composite liner system,a one-dimensional model was developed for solute transport through composite liners containing geomembrane defects.An analytical solution to the model was obtained by the method of Laplace transformation.The results obtained by the presented solution agree well with those obtained by the numerical method.Results show that leachate head and construction quality of geomembrane(GM) have significant influences on the performance of the composite liners for heavy metal ions.The breakthrough time of lead decreases from 50 a to 19 a when the leachate head increases from 0.3 m to 10 m.It is also indicated that the contaminant mass flux of volatile organic compounds(VOCs) induced by leakage can not be neglected in case of poor construction quality of the landfill barrier system.It is shown that diffusion coefficient and partition coefficient of GM have great influences on solute transport through composite liners for VOCs.The breakthrough time of heavy metal ions will be greatly overestimated if the effects of diffusion and adsorption of clay and geosynthetic clay liner(GCL) are neglected.The composite liner consisting of a geomembrane and a GCL provides a poor barrier for VOCs.The presented analytical solution is relatively simple to apply and can be used for preliminary design of composite liners,evaluating experimental results,and verifying more complex numerical models.

  1. In-situ measurement of the heat transport in defect- engineered free-standing single-layer graphene.

    Science.gov (United States)

    Wang, Haidong; Kurata, Kosaku; Fukunaga, Takanobu; Takamatsu, Hiroshi; Zhang, Xing; Ikuta, Tatsuya; Takahashi, Koji; Nishiyama, Takashi; Ago, Hiroki; Takata, Yasuyuki

    2016-01-01

    Utilizing nanomachining technologies, it is possible to manipulate the heat transport in graphene by introducing different defects. However, due to the difficulty in suspending large-area single-layer graphene (SLG) and limited temperature sensitivity of the present probing methods, the correlation between the defects and thermal conductivity of SLG is still unclear. In this work, we developed a new method for fabricating micro-sized suspended SLG. Subsequently, a focused ion beam (FIB) was used to create nanohole defects in SLG and tune the heat transport. The thermal conductivity of the same SLG before and after FIB radiation was measured using a novel T-type sensor method on site in a dual-beam system. The nanohole defects decreased the thermal conductivity by about 42%. It was found that the smaller width and edge scrolling also had significant restriction on the thermal conductivity of SLG. Based on the calculation results through a lattice dynamics theory, the increase of edge roughness and stronger scattering on long-wavelength acoustic phonons are the main reasons for the reduction in thermal conductivity. This work provides reliable data for understanding the heat transport in a defective SLG membrane, which could help on the future design of graphene-based electrothermal devices. PMID:26906476

  2. In-situ measurement of the heat transport in defect- engineered free-standing single-layer graphene

    Science.gov (United States)

    Wang, Haidong; Kurata, Kosaku; Fukunaga, Takanobu; Takamatsu, Hiroshi; Zhang, Xing; Ikuta, Tatsuya; Takahashi, Koji; Nishiyama, Takashi; Ago, Hiroki; Takata, Yasuyuki

    2016-02-01

    Utilizing nanomachining technologies, it is possible to manipulate the heat transport in graphene by introducing different defects. However, due to the difficulty in suspending large-area single-layer graphene (SLG) and limited temperature sensitivity of the present probing methods, the correlation between the defects and thermal conductivity of SLG is still unclear. In this work, we developed a new method for fabricating micro-sized suspended SLG. Subsequently, a focused ion beam (FIB) was used to create nanohole defects in SLG and tune the heat transport. The thermal conductivity of the same SLG before and after FIB radiation was measured using a novel T-type sensor method on site in a dual-beam system. The nanohole defects decreased the thermal conductivity by about 42%. It was found that the smaller width and edge scrolling also had significant restriction on the thermal conductivity of SLG. Based on the calculation results through a lattice dynamics theory, the increase of edge roughness and stronger scattering on long-wavelength acoustic phonons are the main reasons for the reduction in thermal conductivity. This work provides reliable data for understanding the heat transport in a defective SLG membrane, which could help on the future design of graphene-based electrothermal devices.

  3. In-situ measurement of the heat transport in defect- engineered free-standing single-layer graphene

    Science.gov (United States)

    Wang, Haidong; Kurata, Kosaku; Fukunaga, Takanobu; Takamatsu, Hiroshi; Zhang, Xing; Ikuta, Tatsuya; Takahashi, Koji; Nishiyama, Takashi; Ago, Hiroki; Takata, Yasuyuki

    2016-01-01

    Utilizing nanomachining technologies, it is possible to manipulate the heat transport in graphene by introducing different defects. However, due to the difficulty in suspending large-area single-layer graphene (SLG) and limited temperature sensitivity of the present probing methods, the correlation between the defects and thermal conductivity of SLG is still unclear. In this work, we developed a new method for fabricating micro-sized suspended SLG. Subsequently, a focused ion beam (FIB) was used to create nanohole defects in SLG and tune the heat transport. The thermal conductivity of the same SLG before and after FIB radiation was measured using a novel T-type sensor method on site in a dual-beam system. The nanohole defects decreased the thermal conductivity by about 42%. It was found that the smaller width and edge scrolling also had significant restriction on the thermal conductivity of SLG. Based on the calculation results through a lattice dynamics theory, the increase of edge roughness and stronger scattering on long-wavelength acoustic phonons are the main reasons for the reduction in thermal conductivity. This work provides reliable data for understanding the heat transport in a defective SLG membrane, which could help on the future design of graphene-based electrothermal devices. PMID:26906476

  4. Brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) in genetically defined fear-induced aggression.

    Science.gov (United States)

    Ilchibaeva, Tatiana V; Kondaurova, Elena M; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

    2015-09-01

    The brain-derived neurotrophic factor (BDNF), its precursor (proBDNF) and BDNF mRNA levels were studied in the brain of wild rats selectively bred for more than 70 generations for either high level or for the lack of affective aggressiveness towards man. Significant increase of BDNF mRNA level in the frontal cortex and increase of BDNF level in the hippocampus of aggressive rats was revealed. In the midbrain and hippocampus of aggressive rats proBDNF level was increased, whereas BDNF/proBDNF ratio was reduced suggesting the prevalence and increased influence of proBDNF in highly aggressive rats. In the frontal cortex, proBDNF level in aggressive rats was decreased. Thus, considerable structure-specific differences in BDNF and proBDNF levels as well as in BDNF gene expression between highly aggressive and nonaggressive rats were shown. The data suggested the implication of BDNF and its precursor proBDNF in the mechanism of aggressiveness and in the creation of either aggressive or nonaggressive phenotype. PMID:25934485

  5. Impaired TrkB Signaling Underlies Reduced BDNF-Mediated Trophic Support of Striatal Neurons in the R6/2 Mouse Model of Huntington's Disease.

    Science.gov (United States)

    Nguyen, Khanh Q; Rymar, Vladimir V; Sadikot, Abbas F

    2016-01-01

    The principal projection neurons of the striatum are critically dependent on an afferent supply of brain derived neurotrophic factor (BDNF) for neurotrophic support. These neurons express TrkB, the cognate receptor for BDNF, which activates signaling pathways associated with neuronal survival and phenotypic maintenance. Impairment of the BDNF-TrkB pathway is suspected to underlie the early dysfunction and prominent degeneration of striatal neurons in Huntington disease (HD). Some studies in HD models indicate that BDNF supply is reduced, while others suggest that TrkB signaling is impaired earlier in disease progression. It remains important to determine whether a primary defect in TrkB signaling underlies reduced neurotrophic support and the early vulnerability of striatal neurons in HD. Using the transgenic R6/2 mouse model of HD we found that prior to striatal degeneration there are early deficits in striatal protein levels of activated phospho-TrkB and the downstream-regulated protein DARPP-32. In contrast, total-TrkB and BDNF protein levels remained normal. Primary neurons cultured from R6/2 striatum exhibited reduced survival in response to exogenous BDNF applications. Moreover, BDNF activation of phospho-TrkB and downstream signal transduction was attenuated in R6/2 striatal cultures. These results suggest that neurotrophic support of striatal neurons is attenuated early in disease progression due to defects in TrkB signal transduction in the R6/2 model of HD. PMID:27013968

  6. Effects of BDNF Polymorphisms on Antidepressant Action

    OpenAIRE

    Tsai, Shih-Jen; Hong, Chen-Jee; Liou, Ying-Jay

    2010-01-01

    Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidep...

  7. Regulated release of BDNF by cortical oligodendrocytes is mediated through metabotropic glutamate receptors and the PLC pathway

    Directory of Open Access Journals (Sweden)

    Issa P Bagayogo

    2009-04-01

    Full Text Available A number of studies suggest that OLGs (oligodendrocytes), the myelinating cells of the central nervous system, are also a source of trophic molecules, such as neurotrophins that may influence survival of proximate neurons. What is less clear is how the release of these molecules may be regulated. The present study investigated the effects of BDNF (brain-derived neurotrophic factor) derived from cortical OLGs on proximate neurons, as well as regulatory mechanisms mediating BDNF release. Initial work determined that BDNF derived from cortical OLGs increased the numbers of VGLUT1 (vesicular glutamate transporter 1)-positive glutamatergic cortical neurons. Furthermore, glutamate acting through metabotropic, and not AMPA/kainate or NMDA (N-methyl-d-aspartate), receptors increased BDNF release. The PLC (phospholipase C) pathway is a key mediator of metabotropic actions to release BDNF in astrocytes and neurons. Treatment of OLGs with the PLC activator m-3M3FBS [N-(3-trifluoromethylphenyl)-2,4,6-trimethylbenzenesulfonamide] induced robust release of BDNF. Moreover, release elicited by the metabotropic receptor agonist ACPD [trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid] was inhibited by the PLC antagonist U73122, the IP3 (inositol triphosphate 3) receptor inhibitor 2-APB (2-aminoethoxydiphenylborane) and the intracellular calcium chelator BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid tetrakis(acetoxymethyl ester)]. Taken together, these results suggest that OLG lineage cells release BDNF, a molecule trophic for proximate neurons. BDNF release is regulated by glutamate acting through mGluRs (metabotropic glutamate receptors) and the PLC pathway. Thus glutamate and BDNF may be molecules that support neuron–OLG interactions in the cortex.

  8. Influence of brain-derived neurotrophic factor (BDNF) on serotonin neurotransmission in the hippocampus of adult rodents.

    Science.gov (United States)

    Benmansour, Saloua; Deltheil, Thierry; Piotrowski, Jonathan; Nicolas, Lorelei; Reperant, Christelle; Gardier, Alain M; Frazer, Alan; David, Denis J

    2008-06-10

    Whereas SSRIs produce rapid blockade of the serotonin transporter (SERT) in vitro and in vivo, the onset of an observable clinical effect takes longer to occur and a variety of pharmacological effects caused by antidepressants have been speculated to be involved either in initiating antidepressant effects and/or enhancing their effects on serotonergic transmission so as to cause clinical improvement. Among such secondary factors is increased activity of brain-derived neurotrophic factor (BDNF), which requires the Tropomyosine-related kinase B receptor (TrkB) for its effects. To begin an analysis of the influence of BDNF on serotonergic activity, we studied the acute effects of BDNF on SERT activity. A single BDNF injection (either intracerebroventricularly or directly into the CA3 region of hippocampus) decreased the signal amplitude and clearance rate produced by exogenously applied 5-HT compared to what was measured in control rats, shown using in vivo chronoamperometry. It also reduced the ability of a locally applied SSRI to block the clearance of 5-HT. In awake freely moving mice, acute intrahippocampal injection of BDNF decreased extracellular levels of 5-HT in the hippocampus, as measured using microdialysis. In addition, perfusion with BDNF decreased KCl-evoked elevations of 5-HT. These effects of BDNF were blocked by the non-selective antagonist of TrkB receptors, K252a. Overall, it may be inferred that in the hippocampus, through TrkB activation, a single injection of BDNF enhances SERT function. Such acute effects of BDNF would be expected to counter early effects of SSRIs, which might, in part, account for some delay in therapeutic effect. PMID:18474368

  9. BDNF Val66Met Polymorphism Is Associated with Self-Reported Empathy.

    Science.gov (United States)

    Taschereau-Dumouchel, Vincent; Hétu, Sébastien; Bagramian, Anaït; Labrecque, Alexandre; Racine, Marion; Chagnon, Yvon C; Jackson, Philip L

    2016-01-01

    Empathy is an important driver of human social behaviors and presents genetic roots that have been studied in neuroimaging using the intermediate phenotype approach. Notably, the Val66Met polymorphism of the Brain-derived neurotrophic factor (BDNF) gene has been identified as a potential target in neuroimaging studies based on its influence on emotion perception and social cognition, but its impact on self-reported empathy has never been documented. Using a neurogenetic approach, we investigated the association between the BDNF Val66Met polymorphism and self-reported empathy (Davis' Interpersonal Reactivity Index; IRI) in a sample of 110 young adults. Our results indicate that the BDNF genotype is significantly associated with the linear combination of the four facets of the IRI, one of the most widely used self-reported empathy questionnaire. Crucially, the effect of BDNF Val66Met goes beyond the variance explained by two polymorphisms of the oxytocin transporter gene previously associated with empathy and its neural underpinnings (OXTR rs53576 and rs2254298). These results represent the first evidence suggesting a link between the BDNF gene and self-reported empathy and warrant further studies of this polymorphism due to its potential clinical significance. PMID:26901829

  10. Microstructure defects mediated charge transport in Nb-doped epitaxial BaTiO3 thin films

    Science.gov (United States)

    Zhou, Jian; Jing, Xiaosai; Alexe, Marin; Dai, Jiyan; Qin, Minghui; Wu, Sujuan; Zeng, Min; Gao, Jinwei; Lu, Xubing; Liu, J.-M.

    2016-05-01

    Nb-doped BaTiO3 (BNTO) films were deposited on MgO substrates at different substrate temperatures by pulsed laser deposition. The temperature dependence of their resistivity, carrier mobility and carrier concentration were systematically investigated. It reveals that the BNTO films deposited at lower temperature show higher resistivity and lower carrier mobility, and only show semiconductor characteristics at measurement temperatures ranging from 10 to 400 K. There is a metal-semiconductor transition at about 20 K for the films grown at relatively higher temperature. The intrinsic mechanism responsible for the different charge transport behavior was revealed by microstructure studies. Low crystal quality and high density of microstructure defects, observed for BNTO films grown at low temperatures, are, in particular, massively affecting the charge transport behavior of the BNTO films. The mediated charge transport of the microstructure defects is dominated by the thermal excitation process.

  11. Abrogation of the twin arginine transport system in Salmonella enterica serovar Typhimurium leads to colonization defects during infection.

    Science.gov (United States)

    Reynolds, M Megan; Bogomolnaya, Lydia; Guo, Jinbai; Aldrich, Lindsay; Bokhari, Danial; Santiviago, Carlos A; McClelland, Michael; Andrews-Polymenis, Helene

    2011-01-01

    TatC (STM3975) is a highly conserved component of the Twin Arginine Transport (Tat) systems that is required for transport of folded proteins across the inner membrane in gram-negative bacteria. We previously identified a ΔtatC mutant as defective in competitive infections with wild type ATCC14028 during systemic infection of Salmonella-susceptible BALB/c mice. Here we confirm these results and show that the ΔtatC mutant is internalized poorly by cultured J774-A.1 mouse macrophages a phenotype that may be related to the systemic infection defect. This mutant is also defective for short-term intestinal and systemic colonization after oral infection of BALB/c mice and is shed in reduced numbers in feces from orally infected Salmonella-resistant (CBA/J) mice. We show that the ΔtatC mutant is highly sensitive to bile acids perhaps resulting in the defect in intestinal infection that we observe. Finally, the ΔtatC mutant has an unusual combination of motility phenotypes in Salmonella; it is severely defective for swimming motility but is able to swarm well. The ΔtatC mutant has a lower amount of flagellin on the bacterial surface during swimming motility but normal levels under swarming conditions. PMID:21298091

  12. BDNF Genotype Modulates Resting Functional Connectivity in Children

    OpenAIRE

    Thomason, Moriah E.; Daniel J Yoo; Glover, Gary H.; Gotlib, Ian H.

    2009-01-01

    A specific polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met) allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined the association between BDNF gene v...

  13. BDNF genotype modulates resting functional connectivity in children

    OpenAIRE

    Daniel J Yoo; Glover, Gary H.

    2009-01-01

    A specific polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with alterations in brain anatomy and memory; its relevance to the functional connectivity of brain networks, however, is unclear. Given that altered hippocampal function and structure has been found in adults who carry the methionine (met) allele of the BDNF gene and the molecular studies elucidating the role of BDNF in neurogenesis and synapse formation, we examined in the association between BDNF gen...

  14. Decoding BDNF-LTP coupling in cocaine addiction

    OpenAIRE

    Mao, Li-Min; Fibuch, Eugene E.; WANG, John Q.

    2010-01-01

    BDNF is a neurotrophic peptide that regulates synaptic plasticity. New work by Lu and coworkers in this issue of Neuron now identifies BDNF as a gatekeeper of synaptic and behavioral plasticity in cocaine sensitization. In the medial prefrontal cortex, upregulated BDNF facilitates LTP and contributes to neurobehavioral adaptations to psychostimulants.

  15. Decoding BDNF-LTP coupling in cocaine addiction

    Science.gov (United States)

    Mao, Li-Min; Fibuch, Eugene E; Wang, John Q.

    2010-01-01

    BDNF is a neurotrophic peptide that regulates synaptic plasticity. New work by Lu and coworkers in this issue of Neuron now identifies BDNF as a gatekeeper of synaptic and behavioral plasticity in cocaine sensitization. In the medial prefrontal cortex, upregulated BDNF facilitates LTP and contributes to neurobehavioral adaptations to psychostimulants. PMID:20890399

  16. Prenatal Cocaine Exposure Upregulates BDNF-TrkB Signaling.

    Science.gov (United States)

    Stucky, Andres; Bakshi, Kalindi P; Friedman, Eitan; Wang, Hoau-Yan

    2016-01-01

    Prenatal cocaine exposure causes profound changes in neurobehavior as well as synaptic function and structure with compromised glutamatergic transmission. Since synaptic health and glutamatergic activity are tightly regulated by brain-derived neurotrophic factor (BDNF) signaling through its cognate tyrosine receptor kinase B (TrkB), we hypothesized that prenatal cocaine exposure alters BDNF-TrkB signaling during brain development. Here we show prenatal cocaine exposure enhances BDNF-TrkB signaling in hippocampus and prefrontal cortex (PFCX) of 21-day-old rats without affecting the expression levels of TrkB, P75NTR, signaling molecules, NMDA receptor-NR1 subunit as well as proBDNF and BDNF. Prenatal cocaine exposure reduces activity-dependent proBDNF and BDNF release and elevates BDNF affinity for TrkB leading to increased tyrosine-phosphorylated TrkB, heightened Phospholipase C-γ1 and N-Shc/Shc recruitment and higher downstream PI3K and ERK activation in response to ex vivo BDNF. The augmented BDNF-TrkB signaling is accompanied by increases in association between activated TrkB and NMDARs. These data suggest that cocaine exposure during gestation upregulates BDNF-TrkB signaling and its interaction with NMDARs by increasing BDNF affinity, perhaps in an attempt to restore the diminished excitatory neurotransmission. PMID:27494324

  17. Prenatal Cocaine Exposure Upregulates BDNF-TrkB Signaling

    Science.gov (United States)

    Stucky, Andres; Bakshi, Kalindi P.; Friedman, Eitan; Wang, Hoau-Yan

    2016-01-01

    Prenatal cocaine exposure causes profound changes in neurobehavior as well as synaptic function and structure with compromised glutamatergic transmission. Since synaptic health and glutamatergic activity are tightly regulated by brain-derived neurotrophic factor (BDNF) signaling through its cognate tyrosine receptor kinase B (TrkB), we hypothesized that prenatal cocaine exposure alters BDNF-TrkB signaling during brain development. Here we show prenatal cocaine exposure enhances BDNF-TrkB signaling in hippocampus and prefrontal cortex (PFCX) of 21-day-old rats without affecting the expression levels of TrkB, P75NTR, signaling molecules, NMDA receptor—NR1 subunit as well as proBDNF and BDNF. Prenatal cocaine exposure reduces activity-dependent proBDNF and BDNF release and elevates BDNF affinity for TrkB leading to increased tyrosine-phosphorylated TrkB, heightened Phospholipase C-γ1 and N-Shc/Shc recruitment and higher downstream PI3K and ERK activation in response to ex vivo BDNF. The augmented BDNF-TrkB signaling is accompanied by increases in association between activated TrkB and NMDARs. These data suggest that cocaine exposure during gestation upregulates BDNF-TrkB signaling and its interaction with NMDARs by increasing BDNF affinity, perhaps in an attempt to restore the diminished excitatory neurotransmission. PMID:27494324

  18. The effect of topological defects and oxygen adsorption on the electronic transport properties of single-walled carbon-nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Grujicic, M.; Cao, G.; Singh, R

    2003-04-30

    Ab initio density functional theory (DFT) calculations of the interactions between isolated infinitely-long semiconducting zig-zag (10, 0) or isolated infinitely-long metallic arm-chair (5, 5) single-walled carbon-nanotubes (SWCNTs) and single oxygen-molecules are carried out in order to determine the character of molecular-oxygen adsorption and its effect on electronic transport properties of these SWCNTs. A Green's function method combined with a nearest-neighbor tight-binding Hamiltonian in a non-orthogonal basis is used to compute the electrical conductance of SWCNTs and its dependence on the presence of topological defects in SWCNTs and of molecular-oxygen adsorbates. The computational results obtained show that in both semiconducting and metallic SWCNTs, oxygen-molecules are physisorbed to the defect-free nanotube walls, but when such walls contain topological defects, oxygen-molecules become strongly chemisorbed. In semiconducting (10, 0) SWCNTs, physisorbed O{sub 2}-molecules are found to significantly increase electrical conductance while the effect of 7-5-5-7 defects is practically annulled by chemisorbed O{sub 2}-molecules. In metallic (5, 5) SWCNTs, both O{sub 2} adsorbates and 7-5-5-7 defects are found to have a relatively small effect on electrical conductance of these nanotubes.

  19. Intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts

    International Nuclear Information System (INIS)

    Niemann-Pick disease type C (NPC) is characterized by substantial intracellular accumulation of unesterified cholesterol. The accumulation of unesterified cholesterol in NPC fibroblasts cultured with low density lipoprotein (LDL) appears to result from the inability of LDL to stimulate cholesterol esterification in addition to impaired LDL-mediated downregulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in cholesterol transport in NPC cells has been inferred from previous studies, no experiments have been reported that measure the intracellular movement of LDL-cholesterol specifically. We have used four approaches to assess intracellular cholesterol transport in normal and NPC cells and have determined the following: (a) mevinolin-inhibited NPC cells are defective in using LDL-cholesterol for growth. However, exogenously added mevalonate restores cell growth equally in normal and NPC cells; (b) the transport of LDL-derived [3H]cholesterol to the plasma membrane is slower in NPC cells, while the rate of appearance of [3H]acetate-derived, endogenously synthesized [3H]cholesterol at the plasma membrane is the same for normal and NPC cells; (c) in NPC cells, LDL-derived [3H]cholesterol accumulates in lysosomes to higher levels than normal, resulting in defective movement to other cell membranes; and (d) incubation of cells with LDL causes an increase in cholesterol content of NPC lysosomes that is threefold greater than that observed in normal lysosomes. Our results indicate that a cholesterol transport defect exists in NPC that is specific for LDL-derived cholesterol

  20. A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect.

    Science.gov (United States)

    Kosugi, S; Bhayana, S; Dean, H J

    1999-09-01

    We previously reported nine children with an autosomally recessive form of congenital hypothyroidism due to an iodide transport defect in a large Hutterite family with extensive consanguinity living in central Canada. Since the original report, we have diagnosed congenital hypothyroidism by newborn TSH screening in 9 additional children from the family. We performed direct sequencing of the PCR products of each NIS (sodium/iodide symporter) gene exon with flanking introns amplified from genomic DNA extracted from peripheral blood cells of the patients. We identified a novel NIS gene mutation, G395R (Gly395-->Arg; GGA-->AGA), in 10 patients examined in the present study. All of the parents tested were heterozygous for the mutation, suggesting that the patients were homozygous. The mutation was located in the 10th transmembrane helix. Expression experiments by transfection of the mutant NIS complimentary DNA into COS-7 cells showed no perchlorate-sensitive iodide uptake, confirming that the mutation is the direct cause of the iodide transport defect in these patients. A patient who showed an intermediate saliva/serum technetium ratio (14.0; normal, > or = 20) and was considered to have a partial or less severe defect in the previous report (IX-24) did not have a NIS gene mutation. It is now possible to use gene diagnostics of this unique NIS mutation to identify patients with congenital hypothyroidism due to an iodide transport defect in this family and to determine the carrier state of potential parents for genetic counseling and arranging rapid and early diagnosis of their infants. PMID:10487695

  1. Propofol alleviates electroconvulsive shock-induced memory impairment by modulating proBDNF/mBDNF ratio in depressive rats.

    Science.gov (United States)

    Zhang, Fan; Luo, Jie; Min, Su; Ren, Li; Qin, Peipei

    2016-07-01

    This study investigated the effects of propofol and electroconvulsive shock (ECS), the analogue of electroconvulsive therapy (ECT) in animals, on tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as well as the precursor of brain-derived neurotrophic factor (proBDNF)/mature BDNF (mBDNF) ratio in depressive rats. ECT is an effective treatment for depression, but can cause cognitive deficit. Some studies have indicated that propofol can ameliorate cognitive decline induced by ECT, but the underlying molecular mechanism is still unclear. Recent evidence has found that mBDNF and its precursor proBDNF are related to depression and cognitive function; they elicit opposite effects on cellular functions. Chronic unpredicted mild stress is widely used to induce depressive behaviors in rodents. This study found that the depression resulted in an increased expression of PAI-1 and upregulation of the proBDNF/mBDNF ratio, together with a decreased level of tPA, long-term potentiation (LTP) impairment, and cognitive decline. The proBDNF/mBDNF ratio was further upregulated after the ECS treatment in depressive rats, resulting in the deterioration of cognitive function and hippocampal LTP. Propofol alone did not reverse the changes in depressive rats, but when co-administered with ECS, it improved the cognitive function, alleviated the impairment of LTP, downregulated the proBDNF/mBDNF ratio, and increased the tPA expression. The results of this study suggest that propofol ameliorates cognitive decline induced by ECT, which was partly by modulating the proBDNF/mBDNF ratio and reversing the excessive changes in hippocampal synaptic plasticity, providing a new evidence for involving the proBDNF/mBDNF system in the progression and treatment of depression. PMID:27017958

  2. Do Glut1 (glucose transporter type 1) defects exist in epilepsy patients responding to a ketogenic diet?

    Science.gov (United States)

    Becker, Felicitas; Schubert, Julian; Weckhuysen, Sarah; Suls, Arvid; Grüninger, Steffen; Korn-Merker, Elisabeth; Hofmann-Peters, Anne; Sperner, Jürgen; Cross, Helen; Hallmann, Kerstin; Elger, Christian E; Kunz, Wolfram S; Madeleyen, René; Lerche, Holger; Weber, Yvonne G

    2015-08-01

    In the recent years, several neurological syndromes related to defects of the glucose transporter type 1 (Glut1) have been descried. They include the glucose transporter deficiency syndrome (Glut1-DS) as the most severe form, the paroxysmal exertion-induced dyskinesia (PED), a form of spastic paraparesis (CSE) as well as the childhood (CAE) and the early-onset absence epilepsy (EOAE). Glut1, encoded by the gene SLC2A1, is the most relevant glucose transporter in the brain. All Glut1 syndromes respond well to a ketogenic diet (KD) and most of the patients show a rapid seizure control. Ketogenic Diet developed to an established treatment for other forms of pharmaco-resistant epilepsies. Since we were interested in the question if those patients might have an underlying Glut1 defect, we sequenced SLC2A1 in a cohort of 28 patients with different forms of pharmaco-resistant epilepsies responding well to a KD. Unfortunately, we could not detect any mutations in SLC2A1. The exact action mechanisms of KD in pharmaco-resistant epilepsy are not well understood, but bypassing the Glut1 transporter seems not to play an important role. PMID:26088884

  3. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes

    DEFF Research Database (Denmark)

    Krabbe, K. S.; Nielsen, A. R.; Krogh-Madsen, R.;

    2006-01-01

    Aims/hypothesis  Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore...... and a hyperinsulinaemic-euglycaemic clamp. Results  Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism...... and diabetes or obesity. In Study 2 an output of BDNF from the human brain was detected at basal conditions. This output was inhibited when blood glucose levels were elevated. In contrast, when plasma insulin was increased while maintaining normal blood glucose, the cerebral output of BDNF was not inhibited...

  4. BDNF-induced presynaptic facilitation of GABAergic transmission in the hippocampus of young adults is dependent of TrkB and adenosine A2A receptors.

    Science.gov (United States)

    Colino-Oliveira, Mariana; Rombo, Diogo M; Dias, Raquel B; Ribeiro, Joaquim A; Sebastião, Ana M

    2016-06-01

    Brain-derived neurotrophic factor (BDNF) and adenosine are widely recognized as neuromodulators of glutamatergic transmission in the adult brain. Most BDNF actions upon excitatory plasticity phenomena are under control of adenosine A2A receptors (A2ARs). Concerning gamma-aminobutyric acid (GABA)-mediated transmission, the available information refers to the control of GABA transporters. We now focused on the influence of BDNF and the interplay with adenosine on phasic GABAergic transmission. To assess this, we evaluated evoked and spontaneous synaptic currents recorded from CA1 pyramidal cells in acute hippocampal slices from adult rat brains (6 to 10 weeks old). BDNF (10-100 ng/mL) increased miniature inhibitory postsynaptic current (mIPSC) frequency, but not amplitude, as well as increased the amplitude of inhibitory postsynaptic currents (IPSCs) evoked by afferent stimulation. The facilitatory action of BDNF upon GABAergic transmission was lost in the presence of a Trk inhibitor (K252a, 200 nM), but not upon p75(NTR) blockade (anti-p75(NTR) IgG, 50 μg/mL). Moreover, the facilitatory action of BDNF onto GABAergic transmission was also prevented upon A2AR antagonism (SCH 58261, 50 nM). We conclude that BDNF facilitates GABAergic signaling at the adult hippocampus via a presynaptic mechanism that depends on TrkB and adenosine A2AR activation. PMID:26897393

  5. New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brainrelated diseases

    Institute of Scientific and Technical Information of China (English)

    Naoki; Adachi; Tadahiro; Numakawa; Misty; Richards; Shingo; Nakajima; Hiroshi; Kunugi

    2014-01-01

    Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer’s disease, Huntington’s disease, depression and schizophrenia.

  6. Theoretical insights on the electro-thermal transport properties of monolayer MoS2 with line defects

    Science.gov (United States)

    Saha, Dipankar; Mahapatra, Santanu

    2016-04-01

    Two dimensional (2D) materials demonstrate several novel electrical, mechanical, and thermal properties which are quite distinctive to those of their bulk form. Among many others, one important potential application of the 2D material is its use in the field of energy harvesting. Owing to that, here we present a detailed study on electrical as well as thermal transport of monolayer MoS2, in quasi ballistic regime. Besides the perfect monolayer in its pristine form, we also consider various line defects which have been experimentally observed in mechanically exfoliated MoS2 samples. For calculating various parameters related to the electrical transmission, we employ the non-equilibrium Green's function-density functional theory combination. However, to obtain the phonon transmission, we take help of the parametrized Stillinger-Weber potential which can accurately delineate the inter-atomic interactions for the monolayer MoS2. Due to the presence of line defects, we observed significant reductions in both the charge carrier and the phonon transmissions through a monolayer MoS2 flake. Moreover, we also report a comparative analysis showing the temperature dependency of the thermoelectric figure of merit values, as obtained for the perfect as well as the other defective 2D samples.

  7. Thermal transport in UO2 with defects and fission products by molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiang-Yang [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Cooper, Michael William Donald [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mcclellan, Kenneth James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lashley, Jason Charles [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Byler, Darrin David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Stanek, Christopher Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Andersson, Anders David Ragnar [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-14

    The importance of the thermal transport in nuclear fuel has motivated a wide range of experimental and modelling studies. In this report, the reduction of thermal transport in UO2 due to defects and fission products has been investigated using non-equilibrium MD simulations, with two sets of empirical potentials for studying the degregation of UO2 thermal conductivity including a Buckingham type interatomic potential and a recently developed EAM type interatomic potential. Additional parameters for U5+ and Zr4+ in UO2 have been developed for the EAM potential. The thermal conductivity results from MD simulations are then corrected for the spin-phonon scattering through Callaway model formulations. To validate the modelling results, comparison was made with experimental measurements on single crystal hyper-stoichiometric UO2+x samples.

  8. Tratamento da falha óssea parcial pelo transporte ósseo parietal Partial bone defect treatment using parietal bone transportation

    Directory of Open Access Journals (Sweden)

    Fabio Lucas Rodrigues

    2005-01-01

    Full Text Available OBJETIVO: Descrever a técnica de transporte ósseo parietal para tratamento de falha óssea parcial, e descrever o resultado clínico e radiográfico de uma série de pacientes tratados por esta técnica. CASUÍSTICA E MÉTODO: tratamos nove pacientes portadores de lesão óssea parcial, sendo seis localizada na tíbia e três no fêmur. Todos apresentavam lesão infectada, acompanhada de pseudo-artrose. O procedimento iniciou-se com estabilização do segmento ósseo com fixador externo, seguido de corticotomia parietal, em osso sadio adjacente à falha, para criar o fragmento que foi transportado. Este fragmento foi transfixado por fios olivados, que conectados às hastes sulcadas permitiam o transporte ósseo. Em dois pacientes os fragmentos utilizados eram de osso adjacente (fíbula, transportados para a tíbia em direção da tíbia. A latência, velocidade e ritmo de distração foram os preconizados por Ilizarov. RESULTADOS: a infecção e a pseudo-artrose foram curadas em todos os casos, com preenchimento da falha óssea. As complicações encontradas foram infecção nos orifícios dos fios na pele e regenerado hipotrófico. CONCLUSÃO: o tratamento da falha óssea parcial pelo transporte ósseo parietal determinou solução do processo infeccioso, com consolidação da pseudo-artrose e preenchimento da falha óssea.OBJECTIVE: This study describes the bone transportation technique for partial bone defect, and shows clinical and radiological results of a series of patients treated by using this method. MATERIAL AND METHODS: Nine patients with partial bone defect were treated (six tibia and three femur. Every patient had infection and nonunion. The initial procedure was to stabilize the bone, followed by a partial corticotomy on the healthy bone adjacent to the defect, in order to create a fragment to be distracted. This fragment was fixed by olive wires, which were conected to the thread rod. We used fibula transport for tibial lateral

  9. Characterizing defects and transport in Si nanowire devices using Kelvin probe force microscopy

    International Nuclear Information System (INIS)

    Si nanowires (NWs) integrated in a field effect transistor device structure are characterized using scanning electron (SEM), atomic force, and scanning Kelvin probe force (KPFM) microscopy. Reactive ion etching (RIE) and vapor–liquid–solid (VLS) growth were used to fabricate NWs between predefined electrodes. Characterization of Si NWs identified defects and/or impurities that affect the surface electronic structure. RIE NWs have defects that both SEM and KPFM analysis associate with a surface contaminant as well as defects that have a voltage dependent response indicating impurity states in the energy bandgap. In the case of VLS NWs, even after aqua regia, Au impurity levels are found to induce impurity states in the bandgap. KPFM data, when normalized to the oxide-capacitance response, also identify a subset of VLS NWs with poor electrical contact due to nanogaps and short circuits when NWs cross that is not observed in AFM images or in current–voltage measurements when NWs are connected in parallel across electrodes. The experiments and analysis presented outline a systematic method for characterizing a broad array of nanoscale systems under device operation conditions. (paper)

  10. The effect of atomic-scale defects and dopants on phosphorene electronic structure and quantum transport properties.

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Bezanilla, Alejandro

    2016-01-20

    By means of a multi-scale first-principles approach, a description of the local electronic structure of 2D and narrow phosphorene sheets with various types of modifications is presented. Firtly, a rational argument based on the geometry of the pristine and modified P network, and supported by the Wannier functions formalism is introduced to describe a hybridization model of the P atomic orbitals. Ab initio calculations show that non-isoelectronic foreign atoms form quasi-bound states at varying energy levels and create different polarization states depending on the number of valence electrons between P and the doping atom. The quantum transport properties of modified phosphorene ribbons are further described with great accuracy. The distortions on the electronic bands induced by the external species lead to strong backscattering effects on the propagating charge carriers. Depending on the energy of the charge carrier and the type of doping, the conduction may range from the diffusive to the localized regime. Interstitial defects at vacant sites lead to homogeneous transport fingerprints across different types of doping atoms. We suggest that the relatively low values of charge mobility reported in experimental measurements may have its origin in the presence of defects.

  11. Reduced cocaine-seeking behavior in heterozygous BDNF knockout rats

    OpenAIRE

    St. Laurent, Robyn; Helm, Samuel R.; Glenn, Melissa J.

    2013-01-01

    Cocaine generates drug-seeking behavior by creating long-lasting changes in the reward pathway. The role of the growth factor, brain-derived neurotrophic factor (BDNF) in facilitating these changes was investigated in the present report with a genetic rat model. Using conditioned place preference, the current study investigated the hypothesis that a partial knockout of the BDNF gene in rats (BDNF+/−) would attenuate the rewarding effects of cocaine. Wildtype rats exposed to cocaine exhibited ...

  12. The interplay of stress and sleep impacts BDNF level.

    Directory of Open Access Journals (Sweden)

    Maria Giese

    Full Text Available BACKGROUND: Sleep plays a pivotal role in normal biological functions. Sleep loss results in higher stress vulnerability and is often found in mental disorders. There is evidence that brain-derived neurotrophic factor (BDNF could be a central player in this relationship. Recently, we could demonstrate that subjects suffering from current symptoms of insomnia exhibited significantly decreased serum BDNF levels compared with sleep-healthy controls. In accordance with the paradigm indicating a link between sleep and BDNF, we aimed to investigate if the stress system influences the association between sleep and BDNF. METHODOLOGY/PRINCIPAL FINDINGS: Participants with current symptoms of insomnia plus a former diagnosis of Restless Legs Syndrome (RLS and/or Periodic Limb Movement (PLM and sleep healthy controls were included in the study. They completed questionnaires on sleep (ISI, Insomnia Severity Index and stress (PSS, Perceived Stress Scale and provided a blood sample for determination of serum BDNF. We found a significant interaction between stress and insomnia with an impact on serum BDNF levels. Moreover, insomnia severity groups and score on the PSS each revealed a significant main effect on serum BDNF levels. Insomnia severity was associated with increased stress experience affecting serum BDNF levels. Of note, the association between stress and BDNF was only observed in subjects without insomnia. Using a mediation model, sleep was revealed as a mediator of the association between stress experience and serum BDNF levels. CONCLUSIONS: This is the first study to show that the interplay between stress and sleep impacts BDNF levels, suggesting an important role of this relationship in the pathogenesis of stress-associated mental disorders. Hence, we suggest sleep as a key mediator at the connection between stress and BDNF. Whether sleep is maintained or disturbed might explain why some individuals are able to handle a certain stress load while

  13. Adenoviral gene transfer corrects the ion transport defect in the sinus epithelia of a porcine CF model.

    Science.gov (United States)

    Potash, Andrea E; Wallen, Tanner J; Karp, Philip H; Ernst, Sarah; Moninger, Thomas O; Gansemer, Nicholas D; Stoltz, David A; Zabner, Joseph; Chang, Eugene H

    2013-05-01

    Cystic fibrosis (CF) pigs spontaneously develop sinus and lung disease resembling human CF. The CF pig presents a unique opportunity to use gene transfer to test hypotheses to further understand the pathogenesis of CF sinus disease. In this study, we investigated the ion transport defect in the CF sinus and found that CF porcine sinus epithelia lack cyclic AMP (cAMP)-stimulated anion transport. We asked whether we could restore CF transmembrane conductance regulator gene (CFTR) current in the porcine CF sinus epithelia by gene transfer. We quantified CFTR transduction using an adenovirus expressing CFTR and green fluorescent protein (GFP). We found that as little as 7% of transduced cells restored 6% of CFTR current with 17-28% of transduced cells increasing CFTR current to 50% of non-CF levels. We also found that we could overcorrect cAMP-mediated current in non-CF epithelia. Our findings indicate that CF porcine sinus epithelia lack anion transport, and a relatively small number of cells expressing CFTR are required to rescue the ion transport phenotype. These studies support the use of the CF pig as a preclinical model for future gene therapy trials in CF sinusitis. PMID:23511247

  14. Amyloid β oligomers elicit mitochondrial transport defects and fragmentation in a time-dependent and pathway-specific manner.

    Science.gov (United States)

    Rui, Yanfang; Zheng, James Q

    2016-01-01

    Small oligomeric forms of amyloid-β (Aβ) are believed to be the culprit for declined brain functions in AD in part through their impairment of neuronal trafficking and synaptic functions. However, the precise cellular actions of Aβ oligomers and underlying mechanisms in neurons remain to be fully defined. Previous studies have identified mitochondria as a major target of Aβ toxicity contributing to early cognitive decline and memory loss in neurodegenerative diseases including Alzheimer's disease (AD). In this study, we report that Aβ oligomers acutely elicit distinct effects on the transport and integrity of mitochondria. We found that acute exposure of hippocampal neurons to Aβ oligomers from either synthetic peptides or AD brain homogenates selectively impaired fast transport of mitochondria without affecting the movement of late endosomes and lysosomes. Extended exposure of hipoocampal neurons to Aβ oligomers was found to result in mitochondrial fragmentation. While both mitochondrial effects induced by Aβ oligomers can be abolished by the inhibition of GSK3β, they appear to be independent from each other. Aβ oligomers impaired mitochondrial transport through HDAC6 activation whereas the fragmentation involved the GTPase Drp-1. These results show that Aβ oligomers can acutely disrupt mitochondrial transport and integrity in a time-dependent and pathway-specific manner. These findings thus provide new insights into Aβ-induced mitochondrial defects that may contribute to neuronal dysfunction and AD pathogenesis. PMID:27535553

  15. Proteolytic cleavage of proBDNF into mature BDNF in the basolateral amygdala is necessary for defeat-induced social avoidance.

    Science.gov (United States)

    Dulka, Brooke N; Ford, Ellen C; Lee, Melissa A; Donnell, Nathaniel J; Goode, Travis D; Prosser, Rebecca; Cooper, Matthew A

    2016-04-01

    Brain-derived neurotrophic factor (BDNF) is essential for memory processes. The present study tested whether proteolytic cleavage of proBDNF into mature BDNF (mBDNF) within the basolateral amygdala (BLA) regulates the consolidation of defeat-related memories. We found that acute social defeat increases the expression of mBDNF, but not proBDNF, in the BLA/central amygdala. We also showed that blocking plasmin in the BLA with microinjection of α2-antiplasmin immediately following social defeat decreases social avoidance 24 h later. These data suggest the proteolytic cleavage of BDNF in the BLA is necessary for defeat-induced social avoidance. PMID:26980783

  16. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport.

    Science.gov (United States)

    Zhang, Gui-Bin; Wang, Hua; Hu, Jun; Guo, Min-Yin; Wang, Ying; Zhou, Yan; Yu, Zhen; Fu, Lin; Chen, Yuan-Hua; Xu, De-Xiang

    2016-09-01

    Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl2 (2.5 or 5.0mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl2. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters. PMID:27417525

  17. Identification of pristine and defective graphene nanoribbons by phonon signatures in the electron transport characteristics

    DEFF Research Database (Denmark)

    Christensen, Rasmus Bjerregaard; Frederiksen, Thomas; Brandbyge, Mads

    2015-01-01

    Inspired by recent experiments where electron transport was measured across graphene nanoribbons (GNRs) suspended between a metal surface and the tip of a scanning tunneling microscope [Koch, Nat. Nanotechnol.7, 713 (2012)], we present detailed first-principles simulations of inelastic electron t...

  18. Tritium suicide selection of mammalian cell mutants defective in the transport of neutral amino acids

    International Nuclear Information System (INIS)

    Mouse lymphocytic cells of the established line GF-14 were allowed to accumulate intracellular 3H-labeled aminoisobutyric acid (AIB), frozen and stored over liquid N2. After internal radiation had reduced survival to 1 in 104, survivors were plated and tested for their ability to transport AIB. Out of 200 clones tested, two (designated GF-17 and GF-18) were found to have reductions to 13 to 35% of the parent in the rate of transport of AIB, L-alanine, L-proline, and L-serine; GF-18 also showed significant reductions in the rate of transport of L-glutamate and DL-cysteine. Little or no change was observed for 10 other amino acids or for thymidine. Kinetic analyses revealed that the mutants were not altered in K/sub m/ for AIB uptake, but had V/sub max/ values approximately 20% the value of the parent strain, GF-14, suggesting that either the number of AIB transport sites or the turnover rate of the sites has been reduced in the two mutants

  19. Defects, stoichiometry, and electronic transport in SrTiO3-δ epilayers: A high pressure oxygen sputter deposition study

    Science.gov (United States)

    Ambwani, P.; Xu, P.; Haugstad, G.; Jeong, J. S.; Deng, R.; Mkhoyan, K. A.; Jalan, B.; Leighton, C.

    2016-08-01

    SrTiO3 is not only of enduring interest due to its unique dielectric, structural, and lattice dynamical properties, but is also the archetypal perovskite oxide semiconductor and a foundational material in oxide heterostructures and electronics. This has naturally focused attention on growth, stoichiometry, and defects in SrTiO3, one exciting recent development being such precisely stoichiometric defect-managed thin films that electron mobilities have finally exceeded bulk crystals. This has been achieved only by molecular beam epitaxy, however (and to a somewhat lesser extent pulsed laser deposition (PLD)), and numerous open questions remain. Here, we present a study of the stoichiometry, defects, and structure in SrTiO3 synthesized by a different method, high pressure oxygen sputtering, relating the results to electronic transport. We find that this form of sputter deposition is also capable of homoepitaxy of precisely stoichiometric SrTiO3, but only provided that substrate and target preparation, temperature, pressure, and deposition rate are carefully controlled. Even under these conditions, oxygen-vacancy-doped heteroepitaxial SrTiO3 films are found to have carrier density, mobility, and conductivity significantly lower than bulk. While surface depletion plays a role, it is argued from particle-induced X-ray emission (PIXE) measurements of trace impurities in commercial sputtering targets that this is also due to deep acceptors such as Fe at 100's of parts-per-million levels. Comparisons of PIXE from SrTiO3 crystals and polycrystalline targets are shown to be of general interest, with clear implications for sputter and PLD deposition of this important material.

  20. Study of point defects and matter transport in cubic face centered concentrated alloys

    International Nuclear Information System (INIS)

    It is shown that the second moment approximation to the tight binding method allows a functional to be set up which describes transition metals, noble metals and their alloys. It is assumed that the local electronic density of states is rectangular and that the width varies from site to site. It is then shown how the Monte Carlo method can be used to study order in solid solution with a large difference in size between components: atoms of different nature are exchanged and their neighbours are simultaneously displaced in accordance with the microscopic theory of elasticity. The phase diagram of the simulated alloys is then constructed. Experimental results are qualitatively well reproduced but transition temperatures are difficult to evaluate accurately because of a bad estimation of the vibration entropy. A local tendency towards ordering due to chemical effects is shown at the defect proximity. 40 figs., 100 refs

  1. Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11-/- mouse: transport and gene expression studies.

    Science.gov (United States)

    Wang, Renxue; Liu, Lin; Sheps, Jonathan A; Forrest, Dana; Hofmann, Alan F; Hagey, Lee R; Ling, Victor

    2013-08-15

    The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice (abcb11-/-) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11-/- mice. Feeding UDCA to abcb11-/- mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11-/- mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11-/- mice. UDCA fed to abcb11-/- mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11-/- mice. PMID:23764895

  2. Endurance training enhances BDNF release from the human brain

    DEFF Research Database (Denmark)

    Seifert, Thomas; Brassard, Patrice; Wissenberg, Mads;

    2010-01-01

    + or - 108 ng x 100 g(-1) x min(-1) (P < 0.05), with no significant change in the control subjects, but there was no training-induced increase in the release of BDNF during exercise. Additionally, eight mice completed a 5-wk treadmill running training protocol that increased the BDNF mRNA expression in...

  3. A role for BDNF in cocaine reward and relapse

    OpenAIRE

    Schoenbaum, Geoffrey; Stalnaker, Thomas A; Shaham, Yavin

    2007-01-01

    Brain-derived neurotrophic factor (BDNF) is important in regulating synaptic plasticity in the brain areas that process reward information. A new study reports that BDNF in the nucleus accumbens, a brain area critical for the rewarding effects of cocaine, promotes persistent cocaine-seeking behaviors and heightens relapse vulnerability.

  4. Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

    Science.gov (United States)

    Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

    2016-07-01

    Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring. PMID:25940002

  5. Vacancy Defect Reconstruction and its Effect on Electron Transport in Si-C Nanotubes

    Directory of Open Access Journals (Sweden)

    S. Choudhary

    2011-01-01

    Full Text Available We investigate the vacancy defect reconstruction and its effect on I-V characteristics in a (4, 0 zigzag and (5, 5 armchair silicon-carbide nanotubes (SiCNTs by applying self consistent non-equilibrium Green’s function formalism in combination with the density-functional theory to a two probe molecular junction constructed from SiCNTs. The results show that single vacancies and di-vacancies in SiCNTs have different reconstructions. A single vacancy when optimized, reconstructs into a 5-1DB configuration in both zigzag and armchair SiCNTs, and a di-vacancy reconstructs into a 5-8-5 configuration in zigzag and into a 5-2DB configuration in armchair SiCNTs. Introduction of vacancy increases the band gap of (4, 0 metallic SiCNT and decreases the bandgap of (5, 5 semiconducting SiCNT, bias voltage dependent current characteristic show reduction in overall current in metallic SiCNT and an increase in overall current in semiconducting SiCNT.

  6. Working Memory Deficits, Increased Anxiety-Like Traits, and Seizure Susceptibility in BDNF Overexpressing Mice

    Science.gov (United States)

    Papaleo, Francesco; Silverman, Jill L.; Aney, Jordan; Tian, Qingjun; Barkan, Charlotte L.; Chadman, Kathryn K.; Crawley, Jacqueline N.

    2011-01-01

    BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher…

  7. A novel peculiar mutation in the sodium/iodide symporter gene in spanish siblings with iodide transport defect.

    Science.gov (United States)

    Kosugi, Shinji; Okamoto, Hiroomi; Tamada, Aiko; Sanchez-Franco, F

    2002-08-01

    Previously, we reported two Spanish siblings with congenital hypothyroidism due to total failure of iodide transport. These were the only cases reported to date who received long-term iodide treatment over 10 yr. We examined the sodium/iodide symporter (NIS) gene of these patients. A large deletion was observed by long and accurate PCR using primers derived from introns 2 and 7 of the NIS gene. PCR-direct sequencing revealed a deletion of 6192 bases spanning from exon 3 to intron 7 and an inverted insertion of a 431-base fragment spanning from exon 5 to intron 5 of the NIS gene. The patients were homozygous for the mutation, and their mother was heterozygous. In the mutant, deletion of exons 3-7 was suggested by analysis using programs to predict exon/intron organization, resulting in an in-frame 182-amino acid deletion from Met(142) in the fourth transmembrane domain to Gln(323) in the fourth exoplasmic loop. The mutant showed no iodide uptake activity when transfected into COS-7 cells, confirming that the mutation was the direct cause of the iodide transport defect in these patients. Further, the mutant NIS protein was synthesized, but not properly expressed, on the cell surface, but was mostly accumulated in the cytoplasm, suggesting impaired targeting to the plasma membrane. PMID:12161518

  8. Theoretical study of the role of metallic contacts in probing transport features of pure and defected graphene nanoribbons

    Directory of Open Access Journals (Sweden)

    La Magna Antonino

    2011-01-01

    Full Text Available Abstract Understanding the roles of disorder and metal/graphene interface on the electronic and transport properties of graphene-based systems is crucial for a consistent analysis of the data deriving from experimental measurements. The present work is devoted to the detailed study of graphene nanoribbon systems by means of self-consistent quantum transport calculations. The computational formalism is based on a coupled Schrödinger/Poisson approach that respects both chemistry and electrostatics, applied to pure/defected graphene nanoribbons (ideally or end-contacted by various fcc metals. We theoretically characterize the formation of metal-graphene junctions as well as the effects of backscattering due to the presence of vacancies and impurities. Our results evidence that disorder can infer significant alterations on the conduction process, giving rise to mobility gaps in the conductance distribution. Moreover, we show the importance of metal-graphene coupling that gives rise to doping-related phenomena and a degradation of conductance quantization characteristics.

  9. Effect of nonmagnetic defects on superconducting and transport properties of Ba(Fe1–xCoxAs)2 high-Tc superconductors

    International Nuclear Information System (INIS)

    The effect of nonmagnetic defects on superconducting and transport properties of Ba(Fe0.94Co0.06As)2 films is studied for obtaining information on the symmetry type of the order parameter for superconducting pnictides. Such defects are generated in the film by irradiation by He+ ions with an energy of 200 keV. It is found that a decrease in superconducting transition temperature Tc upon an increase in the concentration of nonmagnetic defects in this compound occurs much more slowly than predicted in the model assuming s±-wave symmetry of the order parameter. Joint analysis of the influence of nonmagnetic defects on the superconducting and magnetotransport properties of such films leads to the conclusion that superconductivity is completely suppressed in them after critical disorder is attained, which assumes the s++-wave symmetry

  10. Twin defects in thick stoichiometric lithium tantalate crystals prepared by a vapor transport equilibration method

    Science.gov (United States)

    Yang, Jinfeng; Sun, Jun; Xu, Jingjun; Li, Qinglian; Shang, Jifang; Zhang, Ling; Liu, Shiguo; Huang, Cunxin

    2016-01-01

    The twins were observed and investigated in vapor transport equilibration (VTE) treated lithium tantalate crystals by burying congruent lithium tantalate crystals (CLT) in a Li-rich polycrystalline powder. Twins and their etched patterns were observed under an optical polarizing microscope, and the geometry of the twins was discussed. Twin composition planes were the { 01 1 bar 2 } planes. The cause of twinning was analyzed and verified by experiment. The results indicate that the emergence of twins is due to sintering stress, which arises from sintered Li-rich polycrystalline powders at high temperature. 3.2 mm thick stoichiometric lithium tantalate (SLT) crystals without twins were obtained by setting corundum crucibles over the top of the crystals to make crystals free from the sintering stress. In addition, cracks were observed at the intersection of twin bands, and the stress caused by the dislocation pile-up was considered to be the reason for the formation of cracks.

  11. Recovery of low plasma BDNF over the course of treatment among patients with bulimia nervosa.

    Science.gov (United States)

    Yamada, Hisashi; Yoshimura, Chiho; Nakajima, Takenori; Nagata, Toshihiko

    2012-08-15

    Recent studies have suggested that brain-derived neurotrophic factor (BDNF) is associated with energy balance, eating behaviors, and psychological states such as depression. Although decreased BDNF levels in patients with bulimia nervosa (BN) have been reported, the mechanism is still unclear. Few studies have investigated longitudinal changes of BDNF in BN patients. We investigated changes in the levels of plasma BDNF before and after inpatient treatment. Subjects were 16 female patients with BN and 10 control females. The levels of plasma BDNF were measured. In seven patients who completed a 4-week inpatient treatment program based on cognitive behavior therapy, levels of plasma BDNF were measured twice, before and after inpatient treatment. Plasma BDNF levels were significantly lower in BN subjects than in controls. BDNF levels were significantly higher following inpatient treatment. Increased plasma BDNF after inpatient treatment suggests that lower plasma BDNF levels in BN patients are associated with abnormal eating behaviors, especially binge eating. PMID:22425474

  12. BDNF, produced by a TPO-stimulated megakaryocytic cell line, regulates autocrine proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Shogo [Graduate School of Health Sciences, Hokkaido University, Sapporo (Japan); Research Fellow of the Japan Society for the Promotion of Science, Tokyo (Japan); Nagasawa, Ayumi; Masuda, Yuya; Tsunematsu, Tetsuya [Graduate School of Health Sciences, Hokkaido University, Sapporo (Japan); Hayasaka, Koji; Matsuno, Kazuhiko; Shimizu, Chikara [Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo (Japan); Ozaki, Yukio [Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi (Japan); Moriyama, Takanori, E-mail: moriyama@hs.hokuda.ac.jp [Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo (Japan)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer It has been thought that BDNF is not produced in the megakaryocytic lineage. Black-Right-Pointing-Pointer MEG-01 produces BDNF upon TPO stimulation and regulates its proliferation. Black-Right-Pointing-Pointer BDNF accelerates proliferation of MEG-01 in an autocrine manner. Black-Right-Pointing-Pointer BDNF may be an autocrine MEG-CSF, which regulates megakaryopoiesis. -- Abstract: While human platelets release endogenous brain-derived neurotrophic factor (BDNF) upon activation, a previous report on MEG-01, a megakaryocytic cell line, found no trace of BDNF production, and the pathophysiological function of platelet BDNF has remained elusive. In the present study, we demonstrate that MEG-01 produces BDNF in the presence of TPO and that this serves to potentiate cell proliferation. Our in vitro findings suggest that BDNF regulates MEG-01 proliferation in an autocrine manner, and we suggest that BDNF may be a physiological autocrine regulator of megakaryocyte progenitors.

  13. BDNF, produced by a TPO-stimulated megakaryocytic cell line, regulates autocrine proliferation

    International Nuclear Information System (INIS)

    Highlights: ► It has been thought that BDNF is not produced in the megakaryocytic lineage. ► MEG-01 produces BDNF upon TPO stimulation and regulates its proliferation. ► BDNF accelerates proliferation of MEG-01 in an autocrine manner. ► BDNF may be an autocrine MEG-CSF, which regulates megakaryopoiesis. -- Abstract: While human platelets release endogenous brain-derived neurotrophic factor (BDNF) upon activation, a previous report on MEG-01, a megakaryocytic cell line, found no trace of BDNF production, and the pathophysiological function of platelet BDNF has remained elusive. In the present study, we demonstrate that MEG-01 produces BDNF in the presence of TPO and that this serves to potentiate cell proliferation. Our in vitro findings suggest that BDNF regulates MEG-01 proliferation in an autocrine manner, and we suggest that BDNF may be a physiological autocrine regulator of megakaryocyte progenitors.

  14. Effects of V-shaped edge defect and H-saturation on spin-dependent electronic transport of zigzag MoS2 nanoribbons

    International Nuclear Information System (INIS)

    Based on nonequilibrium Green's function in combination with density functional theory calculations, the spin-dependent electronic transport properties of one-dimensional zigzag molybdenum disulfide (MoS2) nanoribbons with V-shaped defect and H-saturation on the edges have been studied. Our results show that the spin-polarized transport properties can be found in all the considered zigzag MoS2 nanoribbons systems. The edge defects, especially the V-shaped defect on the Mo edge, and H-saturation on the edges can suppress the electronic transport of the systems. Also, the spin-filtering and negative differential resistance behaviors can be observed obviously. The mechanisms are proposed for these phenomena. - Highlights: • The spin-dependent electronic transport of zigzag MoS2 nanoribbons. • The effects of V-shaped edge defect and H-saturation. • The effects of spin-filter and negative differential resistance can be observed

  15. White matter integrity in major depressive disorder: Implications of childhood trauma, 5-HTTLPR and BDNF polymorphisms.

    Science.gov (United States)

    Tatham, Erica L; Ramasubbu, Rajamannar; Gaxiola-Valdez, Ismael; Cortese, Filomeno; Clark, Darren; Goodyear, Bradley; Foster, Jane; Hall, Geoffrey B

    2016-07-30

    This study examined the impact of childhood neglect, serotonin transporter (5-HTTLPR) and brain derived neurotrophic factor (BDNF) polymorphisms on white matter (WM) integrity in major depressive disorder (MDD) using diffusion tensor imaging (DTI). Fifty-five medication-free MDD patients and 18 controls underwent diffusion tensor imaging scanning, genotyping and completed the Childhood Trauma Questionnaire. Tract based spatial statistics (TBSS) findings revealed reduced fractional anisotropy (FA) in the MDD group in the anterior internal capsule. 5-HTTLPR-S'L' heterozygotes in the MDD group exhibited reduced FA in the internal capsule relative to S'S' and reduced FA in corona radiata compared to L'L'. Probabilistic tractography revealed higher FA in the uncinate fasciculus (UF) for BDNF val/val genotype relative to met-carriers, particularly in individuals with high depression severity. High depression severity and experiences of childhood physical or emotional neglect predicted higher FA in the UF and superior longitudinal fasciculus. Reductions in FA were identified for subgroups of MDD patients who were 5-HTTLPR heterozygotes and BDNF-met carriers. An association between emotional/physical neglect and FA was observed in subjects with high depressive symptoms. Our findings suggest that WM connectivity within frontal and limbic regions are affected by depression and influenced by experiences of neglect and genetic risk factors. PMID:27261564

  16. Increased BDNF levels in long-term bipolar disorder patients

    Directory of Open Access Journals (Sweden)

    Izabela Guimarães Barbosa

    2013-03-01

    Full Text Available INTRODUCTION: Bipolar disorder (BD is a prevalent, chronic and progressive illness. There is a growing body of evidence indicating that brain-derived neurotrophic factor (BDNF plays an important role in the pathophysiology of BD. OBJECTIVE: The aim of this study was to evaluate BDNF plasma levels in BD patients with long term illness in comparison with controls. METHODS: 87 BD type I patients and 58 controls matched by age, gender and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of BDNF were measured by ELISA. RESULTS: On average, patients had suffered from BD for 23.4 years. In comparison with controls, BD patients with mania presented a 1.90-fold increase in BDNF plasma levels (p = .001, while BD patients in remission presented a 1.64-fold increase in BDNF plasma levels (p = .03. BDNF plasma levels were not influenced by age, length of illness or current medications. CONCLUSIONS: The present study suggests that long-term BD patients exhibit increased circulating levels of BDNF.

  17. Levels of BDNF Impact Oligodendrocyte Lineage Cells Following a Cuprizone Lesion

    OpenAIRE

    VonDran, Melissa W.; Singh, Harmandeep; Honeywell, Jean Z.; Dreyfus, Cheryl F

    2011-01-01

    Previous work in culture has shown that basal forebrain (BF) oligodendrocyte (OLG) lineage cells respond to BDNF by increasing DNA synthesis and differentiation. Further, in the BF in vivo, reduced levels of BDNF as seen in BDNF +/− mice result in reduced numbers of NG2+ cells and deficits in myelin proteins throughout development and in the adult, suggesting that BDNF impacts the proliferating population of OLGs as well as differentiation in vivo. In this study, to investigate roles BDNF may...

  18. Insulin binding and stimulation of hexose and amino acid transport by normal and receptor-defective human fibroblasts

    International Nuclear Information System (INIS)

    The authors analyzed insulin receptors in cells cultured from a sibship of related parents who had two offspring with severe insulin resistance (Leprechaunism). 124I-Insulin (1 ng/ml) binding to skin fibroblasts from the proband, mother, and father was 9, 60 and 62% of control cells, respectively, at equilibrium, Non-linear regression analysis, utilizing a two receptors model, of curvilinear Scatchard plots indicated a reduced number of high-affinity binding sites in both parents. Influx of L-Proline (System A), L-Serine (ASC) and L-Leucine (L) was similar in control and mutant cells. Similarly, during the depletion of intracellular amino acid pools, there was a release from transinhibition for System A and a decrease of transstimulation of Systems ASC and L in both cell lines. Surprisingly, insulin augmented, normally, A system influx with an ED50 = 70 ng/ml at 240C and 7 ng/ml at 370C. By contrast insulin failed to simulated 3-0-methyl-D-glucose influx into the proband's cells, while normal cells were stimulated 30% with an ED50 of 6 ng/ml. These results indicate that defective high-affinity insulin binding is inherited as an autosomal recessive trait; that general membrane functions are intact; that insulin regulates A system amino acid and hexose transport by two different mechanisms; and, that the latter mechanism is impaired by this family's receptor mutation

  19. A common W556S mutation in the LDL receptor gene of Danish patients with familial hypercholesterolemia encodes a transport-defective protein

    DEFF Research Database (Denmark)

    Jensen, H K; Holst, H; Jensen, L G;

    1997-01-01

    In a group of unrelated Danish patients with familial hypercholesterolemia (FH) we recently reported two common low-density lipoprotein (LDL) receptor mutations, W23X and W66G, accounting for 30% of the cases. In this study, we describe another common LDL receptor mutation, a G to C transition at c...... mutant protein in the endoplasmic reticulum. The transport-defective W556S mutation and the W23X and W66G mutations seem to account for about 40% of the LDL receptor defects in Danish families with FH....

  20. The Control of Electron Transport Related Defects in In Situ Fabricated Single Wall Carbon Nanotube Devices

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Zhixian [ORNL; Jin, Rongying [ORNL; Eres, Gyula [ORNL; Subedi, Alaska P [ORNL; Mandrus, David [ORNL

    2006-01-01

    Metallic single wall carbon nanotube devices were characterized using low temperature transport measurements to study how the growth conditions affect defect formation in carbon nanotubes. Suspended carbon nanotube devices were grown in situ by a molecular beam growth method on a pair of catalyst islands located on opposing Au electrodes fabricated by electron beam lithography. The authors present experimental evidence that defect formation in carbon nanotubes, in addition to the well known growth temperature dependence, is also affected by the nature and the composition of the carbon growth gases.

  1. KINETIC MONTE CARLO SIMULATIONS OF THE EFFECTS OF 1-D DEFECT TRANSPORT ON DEFECT REACTION KINETICS AND VOID LATTICE FORMATION DURING IRRADIATION

    International Nuclear Information System (INIS)

    Within the last decade molecular dynamics simulations of displacement cascades have revealed that glissile clusters of self-interstitial crowdions are formed directly in cascades. Also, under various conditions, a crowdion cluster can change its Burgers vector and glide along a different close-packed direction. In order to incorporate the migration properties of crowdion clusters into analytical rate theory models, it is necessary to describe the reaction kinetics of defects that migrate one-dimensionally with occasional changes in their Burgers vector. To meet this requirement, atomic-scale kinetic Monte Carlo (KMC) simulations have been used to study the defect reaction kinetics of one-dimensionally migrating crowdion clusters as a function of the frequency of direction changes, specifically to determine the sink strengths for such one-dimensionally migrating defects. The KMC experiments are used to guide the development of analytical expressions for use in reaction rate theories and especially to test their validity. Excellent agreement is found between the results of KMC experiments and the analytical expressions derived for the transition from one-dimensional to three-dimensional reaction kinetics. Furthermore, KMC simulations have been performed to investigate the significant role of crowdion clusters in the formation and stability of void lattices. The necessity for both one-dimensional migration and Burgers vectors changes for achieving a stable void lattice is demonstrated.

  2. Functional interactions between steroid hormones and neurotrophin BDNF

    Institute of Scientific and Technical Information of China (English)

    Tadahiro; Numakawa; Daisaku; Yokomaku; Misty; Richards; Hiroaki; Hori; Naoki; Adachi; Hiroshi; Kunugi

    2010-01-01

    Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson’s disease,Alzheimer’s disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson’s disease,Alzheimer’s disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).

  3. Brain derived neurotrophic factor (BDNF contributes to the pain hypersensitivity following surgical incision in the rats

    Directory of Open Access Journals (Sweden)

    Zhang Jian-Yi

    2008-07-01

    Full Text Available Abstract Background The pathogenic role of brain derived neurotrophic factor (BDNF in the incisional pain is poorly understood. The present study explores the role of the BDNF in the incision-induced pain hypersensitivity. Methods A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal root ganglias (DRG and spinal cords were removed at various postoperative times (1–72 h. Expression pattern of BDNF was determined by immunohistochemistry and double-labeling immunofluorescence. Lidocaine-induced blockade of sciatic nerve function was used to determine the importance of afferent nerve activity on BDNF expression in the DRG and spinal cord after incision. BDNF antibody was administered intrathecally (IT or intraperitoneal (IP to modulate the spinal BDNF or peripheral BDNF after incision. Results After hind-paw incision, the BDNF was upregulated in the ipsilateral lumbar DRG and spinal cord whereas thoracic BDNF remained unchanged in response to incision. The upregulated BDNF was mainly expressed in the large-sized neurons in DRG and the neurons and the primary nerve terminals in the spinal cord. Sciatic nerve blockade prevented the increase of BDNF in the DRG and spinal cord. IT injection of BDNF antibody greatly inhibited the mechanical allodynia induced by incision whereas IP administration had only marginal effect. Conclusion The present study showed that incision induced the segmental upregulation of BDNF in the DRG and spinal cord through somatic afferent nerve transmission, and the upregulated BDNF contributed to the pain hypersensitivity induced by surgical incision.

  4. Spike-timing-dependent BDNF secretion and synaptic plasticity.

    Science.gov (United States)

    Lu, Hui; Park, Hyungju; Poo, Mu-Ming

    2014-01-01

    In acute hippocampal slices, we found that the presence of extracellular brain-derived neurotrophic factor (BDNF) is essential for the induction of spike-timing-dependent long-term potentiation (tLTP). To determine whether BDNF could be secreted from postsynaptic dendrites in a spike-timing-dependent manner, we used a reduced system of dissociated hippocampal neurons in culture. Repetitive pairing of iontophoretically applied glutamate pulses at the dendrite with neuronal spikes could induce persistent alterations of glutamate-induced responses at the same dendritic site in a manner that mimics spike-timing-dependent plasticity (STDP)-the glutamate-induced responses were potentiated and depressed when the glutamate pulses were applied 20 ms before and after neuronal spiking, respectively. By monitoring changes in the green fluorescent protein (GFP) fluorescence at the dendrite of hippocampal neurons expressing GFP-tagged BDNF, we found that pairing of iontophoretic glutamate pulses with neuronal spiking resulted in BDNF secretion from the dendrite at the iontophoretic site only when the glutamate pulses were applied within a time window of approximately 40 ms prior to neuronal spiking, consistent with the timing requirement of synaptic potentiation via STDP. Thus, BDNF is required for tLTP and BDNF secretion could be triggered in a spike-timing-dependent manner from the postsynaptic dendrite. PMID:24298135

  5. 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

    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...

  6. Towards a unified biological hypothesis for the BDNF Val66Met-associated memory deficits in humans: a model of impaired dendritic mRNA trafficking

    Directory of Open Access Journals (Sweden)

    Gabriele eBaj

    2013-10-01

    Full Text Available Brain-derived neurotrophic factor (BDNF represents promotesa key molecule for the survival and differentiation of specific populations of neurons in the central nervous system. BDNF also regulates plasticity-related processes underlying memory and learning. A common single nucleotide polymorphism (SNP rs6265 has been identified on the coding sequence of human BDNF located at 11p13. The SNP rs6265 is a single base mutation with an adenine instead of a guanine at position 196 (G196A, resulting in the amino acid substitution Val66Met. This polymorphism only exists in humans and has been associated with a plethora of effects ranging from molecular, cellular and brain structural modifications in association with deficits in social and cognitive functions. To date, the literature on Val66Met polymorphism describes a complex and often conflicting pattern of effects. In this review, we attempt to provide a unifying model of the Val66Met effects. We discuss the clinical evidence of the association between Val66Met and memory deficits, as well as the molecular mechanisms involved including the reduced transport of BDNF mRNA to the dendrites as well as the reduced processing and secretion of BDNF protein through the regulated secretory pathway.

  7. Visible-light photodecomposition of acetaldehyde by TiO2-coated gold nanocages: plasmon-mediated hot electron transport via defect states.

    Science.gov (United States)

    Kodiyath, Rajesh; Manikandan, Maidhily; Liu, Lequan; Ramesh, Gubbala V; Koyasu, Satoshi; Miyauchi, Masahiro; Sakuma, Yoshiki; Tanabe, Toyokazu; Gunji, Takao; Duy Dao, Thang; Ueda, Shigenori; Nagao, Tadaaki; Ye, Jinhua; Abe, Hideki

    2014-12-21

    Skeletal gold nanocages (Au NCs) are synthesized and coated with TiO2 layers (TiO2-Au NCs). The TiO2-Au NCs exhibit enhanced photodecomposition activity toward acetaldehyde under visible light (>400 nm) illumination because hot electrons are generated over the Au NCs by local surface plasmon resonance (LSPR) and efficiently transported across the metal/semiconductor interface via the defect states of TiO2. PMID:25357137

  8. Quantum transport in chemically functionalized graphene at high magnetic field: Defect-Induced Critical States and Breakdown of Electron-Hole Symmetry

    OpenAIRE

    Leconte, Nicolas; Ortmann, Frank; Cresti, Alessandro; Charlier, Jean-Christophe; Roche, Stephan

    2014-01-01

    Unconventional magneto-transport fingerprints in the quantum Hall regime (with applied magnetic field from one to several tens of Tesla) in chemically functionalized graphene are reported. Upon chemical adsorption of monoatomic oxygen (from 0.5% to few percents), the electron-hole symmetry of Landau levels is broken, while a double-peaked conductivity develops at low-energy, resulting from the formation of critical states conveyed by the random network of defects-induced impurity states. Scal...

  9. Development of fabrication technology for future fuel - Study on the defect structure and transport properties of doped U O{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Han Il; Hong, Kug Sun; Lee, Jong Ho; Kang, Sun Ho; Lee, Jung Gun [Seoul National University, Seoul (Korea, Republic of)

    1995-08-01

    The objectives of this project is the study on the defect structure and transport properties on nuclear material to secure the nuclear energy as the substitute source of power. Through this study, we can analyse the effect of dopant in nuclear material thoroughly and further we can establish the basis for the proper processing. And also we can verify the coulometric titration method as a very useful method to characterise the nuclear material. 27 refs., 2 tabs., 7 figs. (author)

  10. Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin.

    Science.gov (United States)

    Wong, Yu-Hui; Lee, Chia-Ming; Xie, Wenjun; Cui, Bianxiao; Poo, Mu-ming

    2015-08-11

    Brain-derived neurotrophic factor (BDNF) is known to modulate synapse development and plasticity, but the source of synaptic BDNF and molecular mechanisms regulating BDNF release remain unclear. Using exogenous BDNF tagged with quantum dots (BDNF-QDs), we found that endocytosed BDNF-QDs were preferentially localized to postsynaptic sites in the dendrite of cultured hippocampal neurons. Repetitive neuronal spiking induced the release of BDNF-QDs at these sites, and this process required activation of glutamate receptors. Down-regulating complexin 1/2 (Cpx1/2) expression eliminated activity-induced BDNF-QD secretion, although the overall activity-independent secretion was elevated. Among eight synaptotagmin (Syt) isoforms examined, down-regulation of only Syt6 impaired activity-induced BDNF-QD secretion. In contrast, activity-induced release of endogenously synthesized BDNF did not depend on Syt6. Thus, neuronal activity could trigger the release of endosomal BDNF from postsynaptic dendrites in a Cpx- and Syt6-dependent manner, and endosomes containing BDNF may serve as a source of BDNF for activity-dependent synaptic modulation. PMID:26216953

  11. Transport limits in defect-engineered LaAlO3/SrTiO3 bilayers

    OpenAIRE

    Gunkel, F.; Wicklein, S.; Hoffmann-Eifert, S.; Meuffels, P.; Brinks, P; Huijben, M.; Waser, R.; Dittmann, R.

    2014-01-01

    The electrical properties of the metallic interface in LaAlO3/SrTiO3 (LAO/STO) bilayers are investigated with focus on the role of cationic defects in thin film STO. Systematic growth-control of the STO thin film cation stoichiometry (defect-engineering) yields a relation between cationic defects in the STO layer and electronic properties of the bilayer-interface. Hall measurements reveal a stoichiometry-effect primarily on the electron mobility. The results indicate an enhancement of scatter...

  12. Exploring the Association between Serum BDNF and Attempted Suicide

    Science.gov (United States)

    Eisen, Rebecca B.; Perera, Stefan; Bawor, Monica; Dennis, Brittany B.; El-Sheikh, Wala; DeJesus, Jane; Rangarajan, Sumathy; Vair, Judith; Sholer, Heather; Hutchinson, Nicole; Iordan, Elizabeth; Mackie, Pam; Islam, Shofiqul; Dehghan, Mahshid; Brasch, Jennifer; Anglin, Rebecca; Minuzzi, Luciano; Thabane, Lehana; Samaan, Zainab

    2016-01-01

    Suicide is a leading cause of death and a significant public health concern. Brain-derived neurotrophic factor (BDNF), a protein important to nervous system function, has been implicated in psychiatric disorders and suicidal behaviour. We investigated the association between serum levels of BDNF and attempted suicide in a sample of 281 participants using a case-control study design. Participants were recruited from clinical and community settings between March 2011 and November 2014. Cases (individuals who had attempted suicide) (n = 84) were matched on sex and age (within five years) to both psychiatric controls (n = 104) and community controls (n = 93) with no history of suicide attempts. We collected fasting blood samples, socio-demographic information, physical measurements, and detailed descriptions of suicide attempts. We used linear regression analysis to determine the association between BDNF level (dependent variable) and attempted suicide (key exposure variable), adjusting for age, sex, body mass index, current smoking status, and antidepressant use. 250 participants were included in this analysis. In the linear regression model, attempted suicide was not significantly associated with BDNF level (β = 0.28, SE = 1.20, P = 0.82). Our findings suggest that no significant association exists between attempted suicide and BDNF level. However, the findings need to be replicated in a larger cohort study. PMID:27121496

  13. Plasma BDNF Concentration, Val66Met Genetic Variant, and Depression-Related Personality Traits

    OpenAIRE

    Terracciano, Antonio; Martin, Bronwen; Ansari, David; Tanaka, Toshiko; Ferrucci, Luigi; Maudsley, Stuart; Mattson, Mark P; Costa, Paul T.

    2010-01-01

    Brain derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurogenesis, and BDNF plasma and serum levels have been associated with depression, Alzheimer's disease, and other psychiatric and neurodegenerative disorders. In a relatively large community sample, drawn from the Baltimore Longitudinal Study of Aging (BLSA), we examine whether BDNF plasma concentration is associated with the Val66Met functional polymorphism of the BDNF gene (n = 335) and with depression-related pers...

  14. Intrinsic limits of channel transport hysteresis in graphene-SiO2 interface and its dependence on graphene defect density

    Science.gov (United States)

    Krishna Bharadwaj, B.; Chandrasekar, Hareesh; Nath, Digbijoy; Pratap, Rudra; Raghavan, Srinivasan

    2016-07-01

    Hysteresis in channel conductance is commonly observed on graphene field effect transistors. Although consistent and repeatable hysteresis could possibly be attractive for memory based applications, it is detrimental to the deployment of graphene in high speed electronic switches. While the origin of such hysteresis has been variously attributed to graphene-insulator interface traps, adsorbed molecules and bulk charges in the dielectric, its dependence on the quality of the graphene has been largely unexplored. Since, CVD is the most promising synthesis route for large area graphene and defects in such a growth process are inevitable, it is important to understand the influence of the quality of graphene on hysteresis. Here we demonstrate, for the first time, the effect of graphene growth defect density on device hysteresis. By intentionally tailoring the defect densities in the growth phase, we demonstrate a linear correlation between the film defect density and conductance hysteresis. The trap charge density calculated from the observed hysteresis in the electrical transfer characteristics was found to both follow the same qualitative trend, and give reasonable quantitative agreement with the defect density as extracted from Raman spectroscopy. Most importantly, by extrapolation from the observed behavior, we identify the intrinsic limits of hysteresis in graphene-SiO2 system, demonstrating that the defects in graphene contribute to traps over and above the baseline set by the SiO2 surface trap charge density.

  15. Comparison of different methods to evaluate and quantify defects of dopamine transporters using 123I FP-CIT

    International Nuclear Information System (INIS)

    Objectives: Several studies have demonstrated the capability of 123I-FPCIT SPECT for studying dopamine transporters in patients with movement disorders. Different techniques have been suggested for semi-quantitative measurement of 123I-FPCIT uptake, based on specific to non specific ratio at equilibrium. Aim of this study was to compare the results of different methods of evaluation. Methods: We performed 123I-FPCIT SPECT scan in 12 patients with Parkinson's disease (PD) and in 3 patients with essential tremor (ET). Images were analysed using 3 different methods: a) visual analysis (0=normal; 0.5=near normal, minimal abnormalities; 1=mild reduced uptake at one or both putamen; 2=severely reduced uptake at both putamen; 3=reduced uptake at caudate and putamen); b) large rectangular ROIs (including entire striatum); c) small irregular ROIs (manually drawn; different for putamen and caudate nucleus). All evaluations were carried out by 3 different operators. Results: Visual analysis and large rectangular ROIs showed the higher reproducibility, while small irregular ROIs were found more affected by operator-dependency. Visual analysis resulted very effective in distinguishing between PD and ET (given 1-3 scores as PD we had 15/15 correct diagnosis); large rectangular ROIs failed in several cases (using a 50% value as cut-off point we had 7/12 correct diagnosis of PE and 3/3 correct diagnosis of ET); small ROIs did not allow to identify a cut-off value enabling to effectively distinguish PD and ET. Conclusions: Reliability and reproducibility of a technique to evaluate 123I-FPCIT SPECT is crucial for its application in routine clinical studies. Our data indicate visual analysis as the more effective method, while the use of approaches based on ROIs, although enabling a semi-quantitative evaluation of defects, were not successful for differential diagnosis. Large ROIs approach was limited by the fact that many PD patients showed a normal uptake at caudate nuclei that

  16. Whole blood BDNF levels in healthy twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Vinberg, Maj; Aznar, Susana;

    2008-01-01

    BACKGROUND: Depression has been associated with decreased blood BDNF concentrations; but it is unclear if low blood BDNF levels are a state or a trait marker of depression. METHODS: We investigated blood BDNF concentrations in a twin population including both subjects highly predisposed and prote...

  17. Transcript-specific effects of adrenalectomy on seizure-induced BDNF expression in rat hippocampus

    DEFF Research Database (Denmark)

    Lauterborn, J C; Poulsen, F R; Stinis, C T;

    1998-01-01

    Activity-induced brain-derived neurotrophic factor (BDNF) expression is negatively modulated by circulating adrenal steroids. The rat BDNF gene gives rise to four major transcript forms that each contain a unique 5' exon (I-IV) and a common 3' exon (V) that codes for BDNF protein. Exon-specific i...

  18. Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown–Vialetto–Van Laere syndrome

    Science.gov (United States)

    Nalini, Atchayaram; Pandraud, Amelie; Mok, Kin; Houlden, Henry

    2013-01-01

    Introduction Madras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. There is a considerable overlap in the phenotype of MMND with Brown–Vialetto–Van Laere syndrome (BVVL) Boltshauser syndrome, Nathalie syndrome and Fazio–Londe syndrome. Recently a number of BVVL cases and families have been described with mutations in two riboflavin transporter genes SLC52A2 and SLC52A3 (solute carrier family 52, riboflavin transporter, member 2 and 3 respectively). Methods and results We describe six families and four sporadic MMND cases that have been clinically characterized in detail with history, examination, imaging and electrophysiological investigations. We sequenced the SLC52A1, SLC52A2 and SLC52A3 in affected probands and sporadic individuals from the MMND series as well as the C9ORF72 expansion. No genetic defects were identified and the C9ORF72 repeats were all less than 10. Conclusions These data suggest that MMND is a distinct clinical subgroup of childhood onset MND patients where the known genetic defects are so far negative. The clinico-genetic features of MMND in comparison with the BVVL group of childhood motor neuron diseases suggest that these diseases are likely to share a common defective biological pathway that may be a combination of genetic and environmental factors. PMID:24139842

  19. YY162 prevents ADHD-like behavioral side effects and cytotoxicity induced by Aroclor1254 via interactive signaling between antioxidant potential, BDNF/TrkB, DAT and NET.

    Science.gov (United States)

    Nam, Yunsung; Shin, Eun-Joo; Shin, Seung Woo; Lim, Yong Kwang; Jung, Jong Ho; Lee, Jeong Hyun; Ha, Jong Ryul; Chae, Jong Seok; Ko, Sung Kwon; Jeong, Ji Hoon; Jang, Choon-Gon; Kim, Hyoung-Chun

    2014-03-01

    Methylphenidate (MP) has become the primary drug of choice for treatment of attention-deficit/hyperactivity disorder (ADHD). However, its psychotropic effects severely hamper long-term clinical use. We evaluated the effects of YY162, which consists of terpenoid-strengthened Ginkgo biloba and ginsenoside Rg3, on the ADHD-like condition induced by Aroclor1254, because both components have been suggested to modulate oxidative stress, dopaminergic neurotransmission, and brain-derived neurotrophic factor (BDNF) signaling, which may be critical targets for understanding the pathogenesis of ADHD. YY162 attenuated the increase in reactive oxygen species (ROS) and decrease in BDNF levels induced by Aroclor1254 in SH-SY5Y neuroblastoma cells. YY162 significantly attenuated Aroclor1254-induced ADHD-like behavior and oxidative stress in ICR mice. Furthermore, YY162 attenuated reductions in p-TrkB, BDNF, dopamine transporter (DAT) and norepinephrine transporter (NET) expression. These attenuating effects of YY162 were comparable to those of MP. Importantly, K252a, a TrkB antagonist, counteracted the protective effects of YY162. Our results suggest that YY162 possesses significant protective activities against ADHD-like conditions with negligible behavioral side effects, and that interactive signaling between antioxidant potential and BDNF/TrkB receptor for the positive modulation of the DAT and NET is important for YY162-mediated neuroprotective activity. PMID:24394491

  20. Effects of phenytoin and lamotrigine treatment on serum BDNF levels in offsprings of epileptic rats.

    Science.gov (United States)

    Soysal, Handan; Doğan, Zümrüt; Kamışlı, Özden

    2016-04-01

    The role of brain-derived neurotrophic factor (BDNF) is to promote and modulate neuronal responses across neurotransmitter systems in the brain. Therefore, abnormal BDNF signaling may be associated with the pathophysiology of schizophrenia. Low BDNF levels have been reported in brains and serums of patients with psychotic disorders. In the present study, we investigated the effects of antiepileptic drugs on BDNF in developing rats. Pregnant rats were treated with phenytoin (PHT), lamotrigine (LTG) and folic acid for long-term, all through their gestational periods. Experimental epilepsy (EE) model was applied in pregnant rats. Epileptic seizures were determined with electroencephalography. After birth, serum BDNF levels were measured in 136 newborn rats on postnatal day (PND) 21 and postnatal day 38. In postnatal day 21, serum BDNF levels of experimental epilepsy group were significantly lower compared with PHT group. This decrease is statistically significant. Serum BDNF levels increased in the group LTG. This increase compared with LTG+EE group was statistically significant. In the folic acid (FA) group, levels of serum BDNF decreased statistically significantly compared to the PHT group. On postnatal day 38, no significant differences were found among the groups for serum BDNF levels. We concluded that, the passed seizures during pregnancy adversely affect fetal brain development, lowering of serum BDNF levels. PHT use during pregnancy prevents seizure-induced injury by increasing the levels of BDNF. About the increase level of BDNF, LTG is much less effective than PHT, the positive effect of folic acid on serum BDNF levels was not observed. LTG increase in BDNF is much less effective than PHT, folic acid did not show a positive effect on serum BDNF levels. Epilepsy affects fetal brain development during gestation in pregnant rats, therefore anti-epileptic therapy should be continued during pregnancy. PMID:26706181

  1. The BDNF Val66Met polymorphism: relation to familiar risk of affective disorder, BDNF levels and salivary cortisol

    DEFF Research Database (Denmark)

    Vinberg, Maj; Trajkovska, Viktorija; Bennike, Bente;

    2009-01-01

    BACKGROUND: Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated with a...... polymorphism may present with an enhanced stress response. The presence of a specific genotype alone may not enhance the risk of developing an affective episode. Rather, the altered stress response may be expressed only in combination with other risk variants through interactions with the environment....... familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol. METHOD: In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified...

  2. Tissue-specific and neural activity-regulated expression of human BDNF gene in BAC transgenic mice

    Directory of Open Access Journals (Sweden)

    Palm Kaia

    2009-06-01

    Full Text Available Abstract Background Brain-derived neurotrophic factor (BDNF is a small secreted protein that has important roles in the developing and adult nervous system. Altered expression or changes in the regulation of the BDNF gene have been implicated in a variety of human nervous system disorders. Although regulation of the rodent BDNF gene has been extensively investigated, in vivo studies regarding the human BDNF gene are largely limited to postmortem analysis. Bacterial artificial chromosome (BAC transgenic mice harboring the human BDNF gene and its regulatory flanking sequences constitute a useful tool for studying human BDNF gene regulation and for identification of therapeutic compounds modulating BDNF expression. Results In this study we have generated and analyzed BAC transgenic mice carrying 168 kb of the human BDNF locus modified such that BDNF coding sequence was replaced with the sequence of a fusion protein consisting of N-terminal BDNF and the enhanced green fluorescent protein (EGFP. The human BDNF-BAC construct containing all BDNF 5' exons preceded by different promoters recapitulated the expression of endogenous BDNF mRNA in the brain and several non-neural tissues of transgenic mice. All different 5' exon-specific BDNF-EGFP alternative transcripts were expressed from the transgenic human BDNF-BAC construct, resembling the expression of endogenous BDNF. Furthermore, BDNF-EGFP mRNA was induced upon treatment with kainic acid in a promotor-specific manner, similarly to that of the endogenous mouse BDNF mRNA. Conclusion Genomic region covering 67 kb of human BDNF gene, 84 kb of upstream and 17 kb of downstream sequences is sufficient to drive tissue-specific and kainic acid-induced expression of the reporter gene in transgenic mice. The pattern of expression of the transgene is highly similar to BDNF gene expression in mouse and human. This is the first study to show that human BDNF gene is regulated by neural activity.

  3. Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model

    Directory of Open Access Journals (Sweden)

    Shuzhen Kong

    2014-01-01

    Full Text Available Cyclothiazide (CTZ has been reported to simultaneously enhance glutamate receptor excitation and inhibit GABAA receptor inhibition, and in turn it evokes epileptiform activities in hippocampal neurons. It has also been shown to acutely induce epileptic seizure behavior in freely moving rats. However, whether CTZ induced seizure rats could develop to have recurrent seizure still remains unknown. In the current study, we demonstrated that 46% of the CTZ induced seizure rats developed to have recurrent seizure behavior as well as epileptic EEG with a starting latency between 2 weeks and several months. In those chronic seizure rats 6 months after the seizure induction by the CTZ, our immunohistochemistry results showed that both GAD and GAT-1 were significantly decreased across CA1, CA3, and dentate gyrus area of the hippocampus studied. In addition, both BDNF and its receptor TrkB were also decreased in hippocampus of the chronic CTZ seizure rats. Our results indicate that CTZ induced seizure is capable of developing to have recurrent seizure, and the decreased GABA synthesis and transport as well as the impaired BDNF-TrkB signaling pathway may contribute to the development of the recurrent seizure. Thus, CTZ seizure rats may provide a novel animal model for epilepsy study and anticonvulsant drug testing in the future.

  4. Defect-dependent carrier transport behavior of polymer:ZnO composites/electrodeposited CdS/indium tin oxide devices

    International Nuclear Information System (INIS)

    Currents through the poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) and ZnO nanoparticles (PEDOT:PSS:ZnO)/CdS/indium tin oxide (ITO) hetero-structures are studied. The authors introduced the electrodeposition technique with sulfide treatment to improve the film quality of CdS. It is shown that sulfide treatment leads to a reduction in the number of donor-like defects (that is, sulfur vacancies and cadmium interstitials) in the CdS films, which leads to the conversion of carrier transport behavior from Poole-Frenkel emission to thermionic emission-diffusion for PEDOT:PSS:ZnO/CdS/ITO devices. A correlation is identified for providing a guide to control the current transport behavior of PEDOT:PSS:ZnO/CdS/ITO devices

  5. Defect-dependent carrier transport behavior of polymer:ZnO composites/electrodeposited CdS/indium tin oxide devices

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yow-Jon, E-mail: rzr2390@yahoo.com.tw; You, C. F. [Institute of Photonics, National Changhua University of Education, Changhua 500, Taiwan (China)

    2015-07-28

    Currents through the poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) and ZnO nanoparticles (PEDOT:PSS:ZnO)/CdS/indium tin oxide (ITO) hetero-structures are studied. The authors introduced the electrodeposition technique with sulfide treatment to improve the film quality of CdS. It is shown that sulfide treatment leads to a reduction in the number of donor-like defects (that is, sulfur vacancies and cadmium interstitials) in the CdS films, which leads to the conversion of carrier transport behavior from Poole-Frenkel emission to thermionic emission-diffusion for PEDOT:PSS:ZnO/CdS/ITO devices. A correlation is identified for providing a guide to control the current transport behavior of PEDOT:PSS:ZnO/CdS/ITO devices.

  6. Correlation of film morphology and defect content with the charge-carrier transport in thin-film transistors based on ZnO nanoparticles

    International Nuclear Information System (INIS)

    The correlation of defect content and film morphology with the charge-carrier transport in field-effect devices based on zinc oxide nanoparticles was investigated. Changes in the defect content and the morphology were realized by annealing and sintering of the nanoparticle thin films. Temperature-dependent electrical measurements reveal that the carrier transport is thermally activated for both the unsintered and sintered thin films. Reduced energetic barrier heights between the particles have been determined after sintering. Additionally, the energetic barrier heights between the particles can be reduced by increasing the drain-to-source voltage and the gate-to-source voltage. The changes in the barrier height are discussed with respect to information obtained by scanning electron microscopy and photoluminescence measurements. It is found that a reduction of surface states and a lower roughness at the interface between the particle layer and the gate dielectric lead to lower barrier heights. Both surface termination and layer morphology at the interface affect the barrier height and thus are the main criteria for mobility improvement and device optimization

  7. Correlation of film morphology and defect content with the charge-carrier transport in thin-film transistors based on ZnO nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Polster, S. [Chair of Electron Devices, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Cauerstrasse 6, 91058 Erlangen (Germany); Jank, M. P. M. [Fraunhofer Institute for Integrated Systems and Device Technology, Schottkystrasse 10, 91058 Erlangen (Germany); Frey, L. [Chair of Electron Devices, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Cauerstrasse 6, 91058 Erlangen (Germany); Fraunhofer Institute for Integrated Systems and Device Technology, Schottkystrasse 10, 91058 Erlangen (Germany)

    2016-01-14

    The correlation of defect content and film morphology with the charge-carrier transport in field-effect devices based on zinc oxide nanoparticles was investigated. Changes in the defect content and the morphology were realized by annealing and sintering of the nanoparticle thin films. Temperature-dependent electrical measurements reveal that the carrier transport is thermally activated for both the unsintered and sintered thin films. Reduced energetic barrier heights between the particles have been determined after sintering. Additionally, the energetic barrier heights between the particles can be reduced by increasing the drain-to-source voltage and the gate-to-source voltage. The changes in the barrier height are discussed with respect to information obtained by scanning electron microscopy and photoluminescence measurements. It is found that a reduction of surface states and a lower roughness at the interface between the particle layer and the gate dielectric lead to lower barrier heights. Both surface termination and layer morphology at the interface affect the barrier height and thus are the main criteria for mobility improvement and device optimization.

  8. Transport of dibasic amino acids, cystine, and tryptophan by cultured human fibroblasts: absence of a defect in cystinuria and Hartnup disease

    Science.gov (United States)

    Groth, Ulrich; Rosenberg, Leon E.

    1972-01-01

    Transport of lysine, arginine, cystine, and tryptophan was studied in cultured skin fibroblasts from normal controls and from patients with cystinuria and Hartnup disease. Each of these amino acids was accumulated against concentration gradients by energy-dependent, saturable mechanisms. Lysine and arginine were each transported by two distinct processes which they shared with each other and with ornithine. In contrast, cystine was taken up by a different transport system with no demonstrable affinity for the dibasic amino acids. The time course and Michaelis-Menten kinetics of lysine and cystine uptake by cells from three cystinuric patients differed in no way from those found in control cells. Similarly, the characteristics of tryptophan uptake by cells from a child with Hartnup disease were identical to those noted in control cells. These findings indicate that the specific transport defects observed in gut and kidney in cystinuria and Hartnup disease are not expressed in cultured human fibroblasts, thus providing additional evidence of the important role that cellular differentiation plays in the regulation of expression of the human genome. PMID:5054467

  9. Autocrine action of BDNF on dendrite development of adult-born hippocampal neurons.

    Science.gov (United States)

    Wang, Liang; Chang, Xingya; She, Liang; Xu, Duo; Huang, Wei; Poo, Mu-ming

    2015-06-01

    Dendrite development of newborn granule cells (GCs) in the dentate gyrus of adult hippocampus is critical for their incorporation into existing hippocampal circuits, but the cellular mechanisms regulating their dendrite development remains largely unclear. In this study, we examined the function of brain-derived neurotrophic factor (BDNF), which is expressed in adult-born GCs, in regulating their dendrite morphogenesis. Using retrovirus-mediated gene transfection, we found that deletion and overexpression of BDNF in adult-born GCs resulted in the reduction and elevation of dendrite growth, respectively. This effect was mainly due to the autocrine rather than paracrine action of BDNF, because deletion of BDNF only in the newborn GCs resulted in dendrite abnormality of these neurons to a similar extent as that observed in conditional knockout (cKO) mice with BDNF deleted in the entire forebrain. Furthermore, selective expression of BDNF in adult-born GCs in BDNF cKO mice fully restored normal dendrite development. The BDNF autocrine action was also required for the development of normal density of spines and normal percentage of spines containing the postsynaptic marker PSD-95, suggesting autocrine BDNF regulation of synaptogenesis. Furthermore, increased dendrite growth of adult-born GCs caused by voluntary exercise was abolished by BDNF deletion specifically in these neurons and elevated dendrite growth due to BDNF overexpression in these neurons was prevented by reducing neuronal activity with coexpression of inward rectifier potassium channels, consistent with activity-dependent autocrine BDNF secretion. Therefore, BDNF expressed in adult-born GCs plays a critical role in dendrite development by acting as an autocrine factor. PMID:26041908

  10. Peripheral Blood Leukocyte Production of BDNF following Mitogen Stimulation in Early Onset and Regressive Autism

    Directory of Open Access Journals (Sweden)

    Amanda Enstrom

    2008-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is critical for neuronal differentiation and synaptic development. BDNF is also implicated in the development of psychological disorders including depression, bipolar disorder and schizophrenia. Previously, elevated BDNF levels were observed in neonatal blood samples from infants who were later diagnosed with autism when compared with children who developed normally, suggesting that BDNF may be involved in the development of autism. BDNF is produced by activated brain microglial cells, a cellular phenotype that shares several features with peripheral macrophages, suggesting an important role for the immune system in BDNF production. We hypothesized that under mitogenic stimulation, peripheral blood mononuclear cells obtained from children with autism may have altered BDNF production compared with age-matched typically developing control subjects. In addition, we examined the differences between the production of BDNF in classic/early-onset autism and children who had a regressive form of autism. We show here that plasma levels of BDNF levels are increased in children with autism, especially in early onset autism subjects. Furthermore, under mitogenic stimulation with PHA and LPS, BDNF production is significantly increased in children with autism compared with typically developing subjects. However, stimulation with tetanus toxoid results in a decreased response in children with autism. This data suggest that immune cell-derived production of BDNF could be an important source for the increased BDNF that is detected in some subjects with autism. As a neurotrophic factor produced by immune cells, BDNF could help elucidate the role of the immune system in neurodevelopment and neuronal maintenance, which may be dysregulated in autism.

  11. Cellular mechanisms of activity-dependent BDNF expression in primary sensory neurons.

    Science.gov (United States)

    Vermehren-Schmaedick, A; Khanjian, R A; Balkowiec, A

    2015-12-01

    Brain-derived neurotrophic factor (BDNF) is abundantly expressed by both developing and adult rat visceral sensory neurons from the nodose ganglion (NG) in vivo and in vitro. We have previously shown that BDNF is released from neonatal NG neurons by activity and regulates dendritic development in their postsynaptic targets in the brainstem. The current study was carried out to examine the cellular and molecular mechanisms of activity-dependent BDNF expression in neonatal rat NG neurons, using our established in vitro model of neuronal activation by electrical field stimulation with patterns that mimic neuronal activity in vivo. We show that BDNF mRNA (transcript 4) increases over threefold in response to a 4-h tonic or bursting pattern delivered at the frequency of 6 Hz, which corresponds to the normal heart rate of a newborn rat. No significant increase in BDNF expression was observed following stimulation at 1 Hz. The latter effect suggests a frequency-dependent mechanism of regulated BDNF expression. In addition to BDNF transcript 4, which is known to be regulated by activity, transcript 1 also showed significant upregulation. The increases in BDNF mRNA were followed by BDNF protein upregulation of a similar magnitude after 24h of stimulation at 6 Hz. Electrical stimulation-evoked BDNF expression was inhibited by pretreating neurons with the blocker of voltage-gated sodium channels tetrodotoxin and by removing extracellular calcium. Moreover, our data show that repetitive stimulation-evoked BDNF expression requires calcium influx through N-, but not L-type, channels. Together, our study reveals novel mechanisms through which electrical activity stimulates de novo synthesis of BDNF in sensory neurons, and points to the role of N-type calcium channels in regulating BDNF expression in sensory neurons in response to repetitive stimulation. PMID:26459016

  12. Copper transport and its defect in Wilson disease: characterization of the copper-binding domain of Wilson disease ATPase.

    Science.gov (United States)

    Sarkar, B

    2000-04-01

    Copper is an essential trace element which forms an integral component of many enzymes. While trace amounts of copper are needed to sustain life, excess copper is extremely toxic. An attempt is made here to present the current understanding of the normal transport of copper in relation to the absorption, intracellular transport and toxicity. Wilson disease is a genetic disorder of copper transport resulting in the accumulation of copper in organs such as liver and brain which leads to progressive hepatic and neurological damage. The gene responsible for Wilson disease (ATP7B) is predicted to encode a putative copper-transporting P-type ATPase. An important feature of this ATPase is the presence of a large N-terminal domain that contains six repeats of a copper-binding motif which is thought to be responsible for binding this metal prior to its transport across the membrane. We have cloned, expressed and purified the N-terminal domain (approximately 70 kD) of Wilson disease ATPase. Metal-binding properties of the domain showed the protein to bind several metals besides copper; however, copper has a higher affinity for the domain. The copper is bound to the domain in Cu(I) form with a copper: protein ratio of 6.5:1. X-ray absorption studies strongly suggest Cu(I) atoms are ligated to cysteine residues. Circular dichroism spectral analyses suggest both secondary and tertiary structural changes upon copper binding to the domain. Copper-binding studies suggest some degree of cooperativity in binding of copper. These studies as well as detailed structural information of the copper-binding domain will be crucial in determining the specific role played by the copper-transporting ATPase in the homeostatic control of copper in the body and how the transport of copper is interrupted by mutations in the ATPase gene. PMID:10830865

  13. Are variations in whole blood BDNF level associated with the BDNF Val66Met polymorphism in patients with first episode depression?

    DEFF Research Database (Denmark)

    Vinberg, Maj; Bukh, Jens Otto Drachmann; Bennike, Bente;

    2013-01-01

    stressful life events (SLE) in a cohort of patients with a first depressive episode. 262 patients with first episode depression (females 174, males 88, age range 18-70, mean age 41) participated and control sample of 84 participants was included (females 52, males 32, age range 22-70, mean age 42......Brain derived neurotrophic factor (BDNF) seems to play an important role in the pathophysiology of affective disorders. The current study investigated whether blood level BDNF is correlated with the severity of depressive symptoms and recent (six months prior to onset of depression) experience of......). Symptomatology was rated using Hamilton Rating Scale for Depression (HAMD-17) and Becks Depression Inventory (BDI 21). No differences in whole blood BDNF was seen in relation to the BDNF Val66Met polymorphism and no significant correlations between whole blood BDNF and HAMD-17 or BDI 21 scores were found. No...

  14. Prefrontal cortical BDNF: A regulatory key in cocaine- and food-reinforced behaviors.

    Science.gov (United States)

    Pitts, Elizabeth G; Taylor, Jane R; Gourley, Shannon L

    2016-07-01

    Brain-derived neurotrophic factor (BDNF) affects synaptic plasticity and neural structure and plays key roles in learning and memory processes. Recent evidence also points to important, yet complex, roles for BDNF in rodent models of cocaine abuse and addiction. Here we examine the role of prefrontal cortical (PFC) BDNF in reward-related decision making and behavioral sensitivity to, and responding for, cocaine. We focus on BDNF within the medial and orbital PFC, its regulation by cocaine during early postnatal development and in adulthood, and how BDNF in turn influences responding for drug reinforcement, including in reinstatement models. When relevant, we draw comparisons and contrasts with experiments using natural (food) reinforcers. We also summarize findings supporting, or refuting, the possibility that BDNF in the medial and orbital PFC regulate the development and maintenance of stimulus-response habits. Further investigation could assist in the development of novel treatment approaches for cocaine use disorders. PMID:26923993

  15. Definition of a Bidirectional Activity-Dependent Pathway Involving BDNF and Narp

    Directory of Open Access Journals (Sweden)

    Abigail Mariga

    2015-12-01

    Full Text Available One of the cardinal features of neural development and adult plasticity is the contribution of activity-dependent signaling pathways. However, the interrelationships between different activity-dependent genes are not well understood. The immediate early gene neuronal-activity-regulated pentraxin (NPTX2 or Narp encodes a protein that has been associated with excitatory synaptogenesis, AMPA receptor aggregation, and the onset of critical periods. Here, we show that Narp is a direct transcriptional target of brain-derived neurotrophic factor (BDNF, another highly regulated activity-dependent gene involved in synaptic plasticity. Unexpectedly, Narp is bidirectionally regulated by BDNF. Acute BDNF withdrawal results in downregulation of Narp, whereas transcription of Narp is greatly enhanced by BDNF. Furthermore, our results show that BDNF directly regulates Narp to mediate glutamatergic transmission and mossy fiber plasticity. Hence, Narp serves as a significant epistatic target of BDNF to regulate synaptic plasticity during periods of dynamic activity.

  16. BDNF promoter methylation and genetic variation in late-life depression

    OpenAIRE

    Januar, V; Ancelin, M-L; Ritchie, K.; Saffery, R.; Ryan, J

    2015-01-01

    The regulation of the brain-derived neurotrophic factor (BDNF) is important for depression pathophysiology and epigenetic regulation of the BDNF gene may be involved. This study investigated whether BDNF methylation is a marker of depression. One thousand and twenty-four participants were recruited as part of a longitudinal study of psychiatric disorders in general population elderly (age⩾65). Clinical levels of depression were assessed using the Mini International Neuropsychiatric Interview ...

  17. BDNF Val66Met is Associated with Introversion and Interacts with 5-HTTLPR to Influence Neuroticism

    OpenAIRE

    Terracciano, Antonio; Tanaka, Toshiko; Sutin, Angelina R.; Deiana, Barbara; Balaci, Lenuta; Sanna, Serena; Olla, Nazario; Maschio, Andrea; Uda, Manuela; Ferrucci, Luigi; Schlessinger, David; Costa, Paul T.

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurotransmission, and has been linked to neuroticism, a major risk factor for psychiatric disorders. A recent genome-wide association (GWA) scan, however, found the BDNF Val66Met polymorphism (rs6265) associated with extraversion but not with neuroticism. In this study, we examine the links between BDNF and personality traits, assessed using the Revised NEO Personality Inventory (NEO-PI-R), in a sample from SardiNIA (...

  18. Association Between MKP-1, BDNF, and Gonadal Hormones with Depression on Perimenopausal Women

    OpenAIRE

    Hui, Ling-Yun; Wang, Ya-Wen; Zhou, Fu-ling; Ma, Xian-cang; Yan, Run-zhi; Zhang, Lin; Wang, Quan-li; Yu, Xuewen

    2016-01-01

    Abstract Background: Studies suggest that brain-derived neurotrophic factor (BDNF) exerts effects on the neuronal function of hippocampal neurons and increases hippocampal mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, which causes depressive behaviors in rat or mouse. Here we focus on the change of serum MKP-1, BDNF, testosterone (T), and estradiol (E2) levels, in order to test the hypothesis that dysregulation of MKP-1, BDNF, T, and E2 are associated with depression in p...

  19. BDNF Methylation and Maternal Brain Activity in a Violence-Related Sample

    OpenAIRE

    Moser, Dominik A.; Ariane Paoloni-Giacobino; Ludwig Stenz; Wafae Adouan; Aurélia Manini; Francesca Suardi; Cordero, Maria I.; Marylene Vital; Ana Sancho Rossignol; Sandra Rusconi-Serpa; François Ansermet; Dayer, Alexandre G.; Schechter, Daniel S.

    2015-01-01

    It is known that increased circulating glucocorticoids in the wake of excessive, chronic, repetitive stress increases anxiety and impairs Brain-Derived Neurotrophic Factor (BDNF) signaling. Recent studies of BDNF gene methylation in relation to maternal care have linked high BDNF methylation levels in the blood of adults to lower quality of received maternal care measured via self-report. Yet the specific mechanisms by which these phenomena occur remain to be established. The present study ex...

  20. GABAA Receptor Blockade Enhances Memory Consolidation by Increasing Hippocampal BDNF Levels

    OpenAIRE

    Kim, Dong hyun; Kim, Jong Min; Park, Se Jin; Cai, MuDan; Liu, Xiaotong; Lee, Seungheon; Shin, Chan Young; Ryu, Jong Hoon

    2011-01-01

    Memory consolidation is the process by which acquired information is converted to something concrete to be retrieved later. Here we examined a potential role for brain-derived neurotrophic factor (BDNF) in mediating the enhanced memory consolidation induced by the GABAA receptor antagonist, bicuculline methiodide. With the administration of an acquisition trial in naïve mice using a passive avoidance task, mature BDNF (mBDNF) levels were temporally changed in the hippocampal CA1 region, and t...

  1. BDNF val66met Polymorphism Affects Aging of Multiple Types of Memory

    OpenAIRE

    Kennedy, Kristen M.; Reese, Elizabeth D.; Horn, Marci M.; Sizemore, April N.; Unni, Asha K.; Meerbrey, Michael E.; Kalich, Allan G.; Rodrigue, Karen M.

    2014-01-01

    The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met poly...

  2. BDNF is Associated With Age-Related Decline in Hippocampal Volume

    OpenAIRE

    Erickson, Kirk I.; Prakash, Ruchika Shaurya; Michelle W Voss; Chaddock, Laura; Heo, Susie; McLaren, Molly; Pence, Brandt D.; Martin, Stephen A.; Vieira, Victoria J.; Jeffrey A. Woods; Kramer, Arthur F.

    2010-01-01

    Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age....

  3. Microglia Control Neuronal Network Excitability via BDNF Signalling

    Directory of Open Access Journals (Sweden)

    Francesco Ferrini

    2013-01-01

    Full Text Available Microglia-neuron interactions play a crucial role in several neurological disorders characterized by altered neural network excitability, such as epilepsy and neuropathic pain. While a series of potential messengers have been postulated as substrates of the communication between microglia and neurons, including cytokines, purines, prostaglandins, and nitric oxide, the specific links between messengers, microglia, neuronal networks, and diseases have remained elusive. Brain-derived neurotrophic factor (BDNF released by microglia emerges as an exception in this riddle. Here, we review the current knowledge on the role played by microglial BDNF in controlling neuronal excitability by causing disinhibition. The efforts made by different laboratories during the last decade have collectively provided a robust mechanistic paradigm which elucidates the mechanisms involved in the synthesis and release of BDNF from microglia, the downstream TrkB-mediated signals in neurons, and the biophysical mechanism by which disinhibition occurs, via the downregulation of the K+-Cl− cotransporter KCC2, dysrupting Cl−homeostasis, and hence the strength of GABAA- and glycine receptor-mediated inhibition. The resulting altered network activity appears to explain several features of the associated pathologies. Targeting the molecular players involved in this canonical signaling pathway may lead to novel therapeutic approach for ameliorating a wide array of neural dysfunctions.

  4. The peculiarities of magnetization processes in layered high- temperature superconductors with ferromagnetic defects under applying of transport current and external magnetic field

    International Nuclear Information System (INIS)

    The Monte-Carlo method was used for study of magnetization processes in 2D layered high temperature superconductors (HTSC) with internal ferromagnetic defects. The magnetization was treated under application of transport current and external dc magnetic field. The voltage-current characteristics (I-V curve) were calculated in presence of external dc magnetic field. A novel S-type I-V curve of the superconductor/ferromagnet system in external magnetic field was demonstrated. It was shown that the S-type nonlinearity is due to the local reversal magnetization of magnetic particles by the field of vortices. The H-T phase diagram which demonstrates the region of existence I-V curve nonlinearity was obtained. The conditions for electromagnetic generation at the region of nonlinearity were found and the frequency of such a generation was estimated

  5. APATHY AND APOE4 ARE ASSOCIATED WITH REDUCED BDNF LEVELS IN ALZHEIMER’S DISEASE

    Science.gov (United States)

    Álvarez, Antón; Aleixandre, Manuel; Linares, Carlos; Masliah, Eliezer; Moessler, Herbert

    2016-01-01

    Reduced brain-derived neurotrophic factor (BDNF) signaling is considered as a pathogenic event in early Alzheimer’s disease (AD), but the influence of apathy and apolipoprotein E epsilon-4 allele (APOE4) on serum BDNF values was not previously investigated in AD. We evaluated serum BDNF levels in AD, amnestic mild cognitive impairment (MCI) and control subjects. Baseline BDNF levels were similar in AD, MCI and controls. AD patients having apathy showed lower BDNF values than patients without apathy (p<0.05). After correction for the influence of apathy, APOE4 carriers showed lower BDNF levels (p<0.01) and MMSE scores (p<0.01) than non-APOE4 carriers in the subgroup of AD females, but not in males. Significant (p<0.05) positive correlations between BDNF values and MMSE scores were only observed in subgroups of AD males and of AD patients without apathy. These results are showing the association of apathy and APOE4 with reduced serum BDNF levels in AD, and are suggesting that BDNF reductions might contribute to the worse cognitive performance exhibited by AD apathetic patients and female APOE4 carriers. PMID:25024337

  6. BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study.

    Science.gov (United States)

    Karamohamed, S; Latourelle, J C; Racette, B A; Perlmutter, J S; Wooten, G F; Lew, M; Klein, C; Shill, H; Golbe, L I; Mark, M H; Guttman, M; Nicholson, G; Wilk, J B; Saint-Hilaire, M; DeStefano, A L; Prakash, R; Tobin, S; Williamson, J; Suchowersky, O; Labell, N; Growdon, B N J; Singer, C; Watts, R; Goldwurm, S; Pezzoli, G; Baker, K B; Giroux, M L; Pramstaller, P P; Burn, D J; Chinnery, P; Sherman, S; Vieregge, P; Litvan, I; Gusella, J F; Myers, R H; Parsian, A

    2005-12-13

    Brain-derived neurotrophic factor (BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-nucleotide polymorphisms in 597 cases of familial PD. Homozygosity for the rare allele of the functional BDNF G196A (Val66Met) variant was associated with a 5.3-year older onset age (p = 0.0001). These findings suggest that BDNF may influence PD onset age. PMID:16344533

  7. BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition

    International Nuclear Information System (INIS)

    Highlights: ► BDNF protected HT-29 colorectal cancer cells from the antitumor effect of cetuximab. ► TrkB inhibition potentiated the antitumor effect of cetuximab. ► BDNF/TrkB signaling might be involved in resistance to anti-EGFR therapy. -- Abstract: The clinical success of targeted treatment of colorectal cancer (CRC) is often limited by resistance to anti-epidermal growth factor receptor (EGFR) therapy. The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB have recently emerged as anticancer targets, and we have previously shown increased BDNF levels in CRC tumor samples. Here we report the findings from in vitro experiments suggesting that BDNF/TrkB signaling can protect CRC cells from the antitumor effects of EGFR blockade. The anti-EGFR monoclonal antibody cetuximab reduced both cell proliferation and the mRNA expression of BDNF and TrkB in human HT-29 CRC cells. The inhibitory effect of cetuximab on cell proliferation and survival was counteracted by the addition of human recombinant BDNF. Finally, the Trk inhibitor K252a synergistically enhanced the effect of cetuximab on cell proliferation, and this effect was blocked by BDNF. These results provide the first evidence that increased BDNF/TrkB signaling might play a role in resistance to EGFR blockade. Moreover, it is possible that targeting TrkB could potentiate the anticancer effects of anti-EGFR therapy.

  8. BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Brunetto de Farias, Caroline [Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); Children' s Cancer Institute, 90420-140 Porto Alegre, RS (Brazil); Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS (Brazil); National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS (Brazil); Heinen, Tiago Elias; Pereira dos Santos, Rafael [Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS (Brazil); National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS (Brazil); Abujamra, Ana Lucia [Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); Children' s Cancer Institute, 90420-140 Porto Alegre, RS (Brazil); National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS (Brazil); Schwartsmann, Gilberto [Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); National Institute for Translational Medicine (INCT-TM), 90035-003 Porto Alegre, RS (Brazil); Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS (Brazil); and others

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer BDNF protected HT-29 colorectal cancer cells from the antitumor effect of cetuximab. Black-Right-Pointing-Pointer TrkB inhibition potentiated the antitumor effect of cetuximab. Black-Right-Pointing-Pointer BDNF/TrkB signaling might be involved in resistance to anti-EGFR therapy. -- Abstract: The clinical success of targeted treatment of colorectal cancer (CRC) is often limited by resistance to anti-epidermal growth factor receptor (EGFR) therapy. The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB have recently emerged as anticancer targets, and we have previously shown increased BDNF levels in CRC tumor samples. Here we report the findings from in vitro experiments suggesting that BDNF/TrkB signaling can protect CRC cells from the antitumor effects of EGFR blockade. The anti-EGFR monoclonal antibody cetuximab reduced both cell proliferation and the mRNA expression of BDNF and TrkB in human HT-29 CRC cells. The inhibitory effect of cetuximab on cell proliferation and survival was counteracted by the addition of human recombinant BDNF. Finally, the Trk inhibitor K252a synergistically enhanced the effect of cetuximab on cell proliferation, and this effect was blocked by BDNF. These results provide the first evidence that increased BDNF/TrkB signaling might play a role in resistance to EGFR blockade. Moreover, it is possible that targeting TrkB could potentiate the anticancer effects of anti-EGFR therapy.

  9. Improvement of chloride transport defect by gonadotropin-releasing hormone (GnRH in cystic fibrosis epithelial cells.

    Directory of Open Access Journals (Sweden)

    Nathalie Benz

    Full Text Available Cystic fibrosis (CF, the most common autosomal recessive disease in Caucasians, is due to mutations in the CFTR gene. F508del, the most frequent mutation in patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER and its traffic to the plasma membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a Cl(- channel function despite a short half-life. Pharmacological treatments may target the F508del-CFTR defect directly by binding to the mutant protein or indirectly by altering cellular proteostasis, and promote its plasma membrane targeting and stability. We previously showed that annexine A5 (AnxA5 directly binds to F508del-CFTR and, when overexpressed, promotes its membrane stability, leading to the restoration of some Cl(- channel function in cells. Because Gonadotropin-Releasing Hormone (GnRH increases AnxA5 expression in some cells, we tested it in CF cells. We showed that human epithelial cells express GnRH-receptors (GnRH-R and that GnRH induces an AnxA5 overexpression and an increased Cl(- channel function in F508del-CFTR cells, due to an increased stability of the protein in the membranes. Beside the numerous physiological implications of the GnRH-R expression in epithelial cells, we propose that a topical use of GnRH is a potential treatment in CF.

  10. Alterations of serum levels of BDNF-related miRNAs in patients with depression.

    Directory of Open Access Journals (Sweden)

    You-Jie Li

    Full Text Available Depression is a serious and potentially life-threatening mental disorder with unknown etiology. Emerging evidence shows that brain-derived neurotrophic factor (BDNF and microRNAs (miRNAs play critical roles in the etiology of depression. Here this study was aimed to identify and characterize the roles of BDNF and its putative regulatory miRNAs in depression. First, we identified that miR-182 may be a putative miRNA that regulates BDNF levels by bioinformatic studies, and characterized the effects of miR-182 on the BDNF levels using cell-based studies, side by side with miR-132 (a known miRNA that regulates BDNF expression. We showed that treatment of miR-132 and miR-182 respectively decreased the BDNF protein levels in a human neuronal cell model, supporting the regulatory roles of miR-132 and miR-182 on the BDNF expression. Furthermore, we explored the roles of miR-132 and miR-182 on the BDNF levels in depression using human subjects by assessing their serum levels. Compared with the healthy controls, patients with depression showed lower serum BDNF levels (via the enzyme-linked immunosorbent assays and higher serum miR-132 and miR-182 levels (via the real-time PCR. Finally, the Pearson's (or Spearman's correlation coefficient was calculated to study whether there was a relationship among the Self-Rating Depression Scale score, the serum BDNF levels, and serum BDNF-related miRNA levels. Our results revealed that there was a significant negative correlation between the SDS scores and the serum BDNF levels, and a positive correlation between the SDS scores and miR-132 levels. In addition, we found a reverse relationship between the serum BDNF levels and the miR-132/miR-182 levels in depression. Collectively, we provided evidence supporting that miR-182 is a putative BDNF-regulatory miRNA, and suggested that the serum BDNF and its related miRNAs may be utilized as important biomarkers in the diagnosis or as therapeutic targets of depression.

  11. Control of spine maturation and pruning through proBDNF synthesized and released in dendrites.

    Science.gov (United States)

    Orefice, Lauren L; Shih, Chien-Cheng; Xu, Haifei; Waterhouse, Emily G; Xu, Baoji

    2016-03-01

    Excess synapses formed during early postnatal development are pruned over an extended period, while the remaining synapses mature. Synapse pruning is critical for activity-dependent refinement of neuronal connections and its dysregulation has been found in neurodevelopmental disorders such as autism spectrum disorders; however, the mechanism underlying synapse pruning remains largely unknown. As dendritic spines are the postsynaptic sites for the vast majority of excitatory synapses, spine maturation and pruning are indicators for maturation and elimination of these synapses. Our previous studies have found that dendritically localized mRNA for brain-derived neurotrophic factor (BDNF) regulates spine maturation and pruning. Here we investigated the mechanism by which dendritic Bdnf mRNA, but not somatically restricted Bdnf mRNA, promotes spine maturation and pruning. We found that neuronal activity stimulates both translation of dendritic Bdnf mRNA and secretion of its translation product mainly as proBDNF. The secreted proBDNF promotes spine maturation and pruning, and its effect on spine pruning is in part mediated by the p75(NTR) receptor via RhoA activation. Furthermore, some proBDNF is extracellularly converted to mature BDNF and then promotes maturation of stimulated spines by activating Rac1 through the TrkB receptor. In contrast, translation of somatic Bdnf mRNA and the release of its translation product mainly as mature BDNF are independent of action potentials. These results not only reveal a biochemical pathway regulating synapse pruning, but also suggest that BDNF synthesized in the soma and dendrites is released through distinct secretory pathways. PMID:26705735

  12. Immunohistochemical, ultrastructural and functional analysis of axonal regeneration through peripheral nerve grafts containing Schwann cells expressing BDNF, CNTF or NT3.

    Directory of Open Access Journals (Sweden)

    Maria João Godinho

    Full Text Available We used morphological, immunohistochemical and functional assessments to determine the impact of genetically-modified peripheral nerve (PN grafts on axonal regeneration after injury. Grafts were assembled from acellular nerve sheaths repopulated ex vivo with Schwann cells (SCs modified to express brain-derived neurotrophic factor (BDNF, a secretable form of ciliary neurotrophic factor (CNTF, or neurotrophin-3 (NT3. Grafts were used to repair unilateral 1 cm defects in rat peroneal nerves and 10 weeks later outcomes were compared to normal nerves and various controls: autografts, acellular grafts and grafts with unmodified SCs. The number of regenerated βIII-Tubulin positive axons was similar in all grafts with the exception of CNTF, which contained the fewest immunostained axons. There were significantly lower fiber counts in acellular, untransduced SC and NT3 groups using a PanNF antibody, suggesting a paucity of large caliber axons. In addition, NT3 grafts contained the greatest number of sensory fibres, identified with either IB4 or CGRP markers. Examination of semi- and ultra-thin sections revealed heterogeneous graft morphologies, particularly in BDNF and NT3 grafts in which the fascicular organization was pronounced. Unmyelinated axons were loosely organized in numerous Remak bundles in NT3 grafts, while the BDNF graft group displayed the lowest ratio of umyelinated to myelinated axons. Gait analysis revealed that stance width was increased in rats with CNTF and NT3 grafts, and step length involving the injured left hindlimb was significantly greater in NT3 grafted rats, suggesting enhanced sensory sensitivity in these animals. In summary, the selective expression of BDNF, CNTF or NT3 by genetically modified SCs had differential effects on PN graft morphology, the number and type of regenerating axons, myelination, and locomotor function.

  13. Effect of nonmagnetic defects on superconducting and transport properties of Ba(Fe{sub 1–x}Co{sub x}As){sub 2} high-T{sub c} superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Blokhin, I. S.; Gavrilkin, S. Yu. [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation); Gorshunov, B. P. [Russian Academy of Sciences, Prokhorov General Physics Institute (Russian Federation); Dravin, V. A. [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation); Zhukova, E. S. [Russian Academy of Sciences, Prokhorov General Physics Institute (Russian Federation); Ivanenko, O. M. [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation); Aida, K. [Leibniz Institute for Solid State and Materials Research (Germany); Krasnosvobodtsev, S. I. [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation); Kurt, F. [Leibniz Institute for Solid State and Materials Research (Germany); Mitsen, K. V., E-mail: mitsen@sci.lebedev.ru; Tsvetkov, A. Yu. [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation)

    2015-11-15

    The effect of nonmagnetic defects on superconducting and transport properties of Ba(Fe{sub 0.94}Co{sub 0.06}As){sub 2} films is studied for obtaining information on the symmetry type of the order parameter for superconducting pnictides. Such defects are generated in the film by irradiation by He{sup +} ions with an energy of 200 keV. It is found that a decrease in superconducting transition temperature T{sub c} upon an increase in the concentration of nonmagnetic defects in this compound occurs much more slowly than predicted in the model assuming s{sup ±}-wave symmetry of the order parameter. Joint analysis of the influence of nonmagnetic defects on the superconducting and magnetotransport properties of such films leads to the conclusion that superconductivity is completely suppressed in them after critical disorder is attained, which assumes the s{sup ++}-wave symmetry.

  14. Role of BDNF in bipolar and unipolar disorder: clinical and theoretical implications.

    Science.gov (United States)

    Post, Robert M

    2007-12-01

    A number of lines of converging evidence suggest that brain-derived neurotrophic factor (BDNF) may play a role in the onset and treatment of bipolar disorder. We review pertinent data on BDNF from several different areas of preclinical and clinical investigation that suggest novel theoretical and treatment implications for the recurrent affective disorders. Data from several recent studies have also converged showing that the val66met allele of BDNF, a common single nucleotide polymorphism (SNP), is associated with selective minor deficits in cognitive functioning in subjects with schizophrenia, bipolar illness, and normal controls. Yet, paradoxically, the better functioning val66val allele of BDNF appears to be associated with an increased risk for bipolar disorder and perhaps early onset or rapid cycling. All the primary antidepressant modalities, as well as the mood stabilizers lithium and valproate, increase BDNF. Stressors decrease BDNF and this effect can be blocked by antidepressants. Serum BDNF is low in proportion to the severity of mania and depression and increases with clinical improvement. Assessment of the val66val BDNF allele and a range of other SNPs as potential vulnerability factors for bipolar illness and its early onset could facilitate studies of early intervention, help reduce long delays between the onset of first symptoms and the first treatment, and help in the prediction of individual patient's likelihood of responding to a given treatment. PMID:17239400

  15. Age-Dependent Deficits in Fear Learning in Heterozygous BDNF Knock-Out Mice

    Science.gov (United States)

    Endres, Thomas; Lessmann, Volkmar

    2012-01-01

    Beyond its trophic function, the neurotrophin BDNF (brain-derived neurotrophic factor) is well known to crucially mediate synaptic plasticity and memory formation. Whereas recent studies suggested that acute BDNF/TrkB signaling regulates amygdala-dependent fear learning, no impairments of cued fear learning were reported in heterozygous BDNF…

  16. BDNF Val66Met polymorphism and protein levels in Amniotic Fluid

    Directory of Open Access Journals (Sweden)

    Calabrese Francesca

    2010-02-01

    Full Text Available Abstract Background Brain-Derived Neurotrophic Factor (BDNF is a neurotrophin which plays survival- and growth-promoting activity in neuronal cells and it is involved in cellular plasticity mechanisms as it controls activity dependent synaptic transmission. A functional polymorphism (Val66Met in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF has been associated with memory and cognitive deficits as well as to an increased susceptibility for several psychiatric disorders especially those with a neurodevelopmental origin. To date, no study has evaluated the influence of the Val66Met polymorphism on BDNF levels in a peripheral system that may reflect fetal neurodevelopment. Therefore we investigated in amniotic fluids (AF obtained from 139 healthy women during 15-17 week of pregnancy, BDNF protein levels in correlation with the Val66Met polymorphism. Results Interestingly we found a significant BDNF protein levels reduction in 55 Met carriers (Val/Met and Met/Met (p = 0.002 as compared to 84 non carriers (Val/Val, and no effect of fetus gender, maternal age or gestation week on BDNF levels has been observed. Conclusion These results, although explorative, indicate that during fetal life the Val66Met genotype might influences BDNF protein levels in AF supporting the involvement of this polymorphism in behavioral and functional brain individual differences in the adulthood.

  17. BDNF mediates improvements in executive function following a 1-year exercise intervention

    Directory of Open Access Journals (Sweden)

    Regina Lynn Leckie

    2014-12-01

    Full Text Available Executive function declines with age, but engaging in aerobic exercise may attenuate decline. One mechanism by which aerobic exercise may preserve executive function is through the up-regulation of brain-derived neurotropic factor (BDNF, which also declines with age. The present study examined BDNF as a mediator of the effects of a 1-year walking intervention on executive function in 90 older adults (mean age = 66.82. Participants were randomized to a stretching and toning control group or a moderate intensity walking intervention group. BDNF serum levels and performance on a task-switching paradigm were collected at baseline and follow-up. We found that age moderated the effect of intervention group on changes in BDNF levels, with those in the highest age quartile showing the greatest increase in BDNF after 1-year of moderate intensity walking exercise (p = .036. The mediation analyses revealed that BDNF mediated the effect of the intervention on task-switch accuracy, but did so as a function of age, such that exercise-induced changes in BDNF mediated the effect of exercise on task-switch performance only for individuals over the age of 71. These results demonstrate that both age and BDNF serum levels are important factors to consider when investigating the mechanisms by which exercise interventions influence cognitive outcomes, particularly in elderly populations.

  18. BDNF mediates improvements in executive function following a 1-year exercise intervention.

    Science.gov (United States)

    Leckie, Regina L; Oberlin, Lauren E; Voss, Michelle W; Prakash, Ruchika S; Szabo-Reed, Amanda; Chaddock-Heyman, Laura; Phillips, Siobhan M; Gothe, Neha P; Mailey, Emily; Vieira-Potter, Victoria J; Martin, Stephen A; Pence, Brandt D; Lin, Mingkuan; Parasuraman, Raja; Greenwood, Pamela M; Fryxell, Karl J; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F; Erickson, Kirk I

    2014-01-01

    Executive function declines with age, but engaging in aerobic exercise may attenuate decline. One mechanism by which aerobic exercise may preserve executive function is through the up-regulation of brain-derived neurotropic factor (BDNF), which also declines with age. The present study examined BDNF as a mediator of the effects of a 1-year walking intervention on executive function in 90 older adults (mean age = 66.82). Participants were randomized to a stretching and toning control group or a moderate intensity walking intervention group. BDNF serum levels and performance on a task-switching paradigm were collected at baseline and follow-up. We found that age moderated the effect of intervention group on changes in BDNF levels, with those in the highest age quartile showing the greatest increase in BDNF after 1-year of moderate intensity walking exercise (p = 0.036). The mediation analyses revealed that BDNF mediated the effect of the intervention on task-switch accuracy, but did so as a function of age, such that exercise-induced changes in BDNF mediated the effect of exercise on task-switch performance only for individuals over the age of 71. These results demonstrate that both age and BDNF serum levels are important factors to consider when investigating the mechanisms by which exercise interventions influence cognitive outcomes, particularly in elderly populations. PMID:25566019

  19. Whole blood BDNF levels in healthy twins discordant for affective disorder: association to life events and neuroticism

    DEFF Research Database (Denmark)

    Trajkovska, V.; Vinberg, M.; Aznar, S.;

    2008-01-01

    BACKGROUND: Depression has been associated with decreased blood BDNF concentrations; but it is unclear if low blood BDNF levels are a state or a trait marker of depression. METHODS: We investigated blood BDNF concentrations in a twin population including both subjects highly predisposed and prote...

  20. Defect modelling

    International Nuclear Information System (INIS)

    Calculations, drawing principally on developments at AERE Harwell, of the relaxation about lattice defects are reviewed with emphasis on the techniques required for such calculations. The principles of defect modelling are outlined and various programs developed for defect simulations are discussed. Particular calculations for metals, ionic crystals and oxides, are considered. (UK)

  1. Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction.

    Science.gov (United States)

    Chen, Jeremy Tsung-chieh; Guo, Da; Campanelli, Dario; Frattini, Flavia; Mayer, Florian; Zhou, Luming; Kuner, Rohini; Heppenstall, Paul A; Knipper, Marlies; Hu, Jing

    2014-01-01

    The gate control theory proposes the importance of both pre- and post-synaptic inhibition in processing pain signal in the spinal cord. However, although postsynaptic disinhibition caused by brain-derived neurotrophic factor (BDNF) has been proved as a crucial mechanism underlying neuropathic pain, the function of presynaptic inhibition in acute and neuropathic pain remains elusive. Here we show that a transient shift in the reversal potential (EGABA) together with a decline in the conductance of presynaptic GABAA receptor result in a reduction of presynaptic inhibition after nerve injury. BDNF mimics, whereas blockade of BDNF signalling reverses, the alteration in GABAA receptor function and the neuropathic pain syndrome. Finally, genetic disruption of presynaptic inhibition leads to spontaneous development of behavioural hypersensitivity, which cannot be further sensitized by nerve lesions or BDNF. Our results reveal a novel effect of BDNF on presynaptic GABAergic inhibition after nerve injury and may represent new strategy for treating neuropathic pain. PMID:25354791

  2. Serum brain-derived neurotrophic factor (BDNF) is not regulated by testosterone in transmen.

    Science.gov (United States)

    Auer, Matthias K; Hellweg, Rainer; Briken, Peer; Stalla, Günter K; T'Sjoen, Guy; Fuss, Johannes

    2016-01-01

    Brain morphology significantly differs between the sexes. It has been shown before that some of these differences are attributable to the sex-specific hormonal milieu. Brain-derived neurotrophic factor (BDNF) is involved in myriads of neuroplastic processes and shows a sexual dimorphism. Transsexual persons may serve as a model to study sex steroid-mediated effects on brain plasticity. We have recently demonstrated that serum levels of BDNF are reduced in transwomen following 12 months of cross-sex hormone treatment. We now wanted to look at the effects of testosterone treatment on BDNF in transmen. In contrast to our initial hypothesis, BDNF levels did not significantly change, despite dramatic changes in the sex-hormonal milieu. Our data indicate that testosterone does not seem to play a major role in the regulation of BDNF in females. PMID:26753091

  3. Possible Role of Brain-Derived Neurotrophic Factor (BDNF) in Autism Spectrum Disorder: Current Status

    International Nuclear Information System (INIS)

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays a vital role in the growth, development, maintenance, and function of several neuronal systems. The purpose of this review is to document the support for the involvement of this molecule in the maintenance of normal cognitive, emotional functioning, and to outline recent developments in the content of Autism spectrum disorder (ASD). Current and future treatment development can be guided by developing understanding of this molecules actions in the brain and the ways the expression of BDNF can be planned. Over the years, research findings suggested a critical role played by BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals. (author)

  4. ASPECTS OF CYCLON AND BDNF GENE EXPRESSION IN SCHIZOPHRENIA PATIENTS

    Directory of Open Access Journals (Sweden)

    Rinaldo Shishkov

    2012-08-01

    Full Text Available The pathogenesis of the schizophrenic illness is still not fully elucidated. Many studies have been conducted revealing different aspects but may be the studies of greatest significance are studying the genetic aspects of expression of trophic factors and enzymes associated with nervous system development and plasticity. In this relation we aimed at measuring the Cyclon and BDNF genes expression in blood of patients suffering from schizophrenia and to test for correlation between them. Our result did not reveal correlation in spite of their connection with the disease

  5. Brain BDNF levels are dependent on cerebrovascular endothelium-derived nitric oxide.

    Science.gov (United States)

    Banoujaafar, Hayat; Monnier, Alice; Pernet, Nicolas; Quirié, Aurore; Garnier, Philippe; Prigent-Tessier, Anne; Marie, Christine

    2016-09-01

    Scientific evidence continues to demonstrate a link between endothelial function and cognition. Besides, several studies have identified a complex interplay between nitric oxide (NO) and brain-derived neurotrophic factor (BDNF), a neurotrophin largely involved in cognition. Therefore, this study investigated the link between cerebral endothelium-derived NO and BDNF signaling. For this purpose, levels of BDNF and the phosphorylated form of endothelial NO synthase at serine 1177 (p-eNOS) were simultaneously measured in the cortex and hippocampus of rats subjected to either bilateral common carotid occlusion (n = 6), physical exercise (n = 6) or a combination of both (n = 6) as experimental approaches to modulate flow-induced NO production by the cerebrovasculature. Tropomyosin-related kinase type B (TrkB) receptors and its phosphorylated form at tyrosine 816 (p-TrkB) were also measured. Moreover, we investigated BDNF synthesis in brain slices exposed to the NO donor glyceryl trinitrate. Our results showed increased p-eNOS and BDNF levels after exercise and decreased levels after vascular occlusion as compared to corresponding controls, with a positive correlation between changes in p-eNOS and BDNF (r = 0.679). Exercise after vascular occlusion did not change levels of these proteins. Gyceryl trinitrate increased proBDNF and BDNF levels in brain slices, thus suggesting a possible causal relationship between NO and BDNF. Moreover, vascular occlusion, like exercise, resulted in increased TrkB and p-TrkB levels, whereas no change was observed with the combination of both. These results suggest that brain BDNF signaling may be dependent on cerebral endothelium-derived NO production. PMID:27306299

  6. Effect of dietary fat and the circadian clock on the expression of brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Genzer, Yoni; Dadon, Maayan; Burg, Chen; Chapnik, Nava; Froy, Oren

    2016-07-15

    Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the brain and its decreased levels are associated with the development of obesity and neurodegeneration. Our aim was to test the effect of dietary fat, its timing and the circadian clock on the expression of BDNF and associated signaling pathways in mouse brain and liver. Bdnf mRNA oscillated robustly in brain and liver, but with a 12-h shift between the tissues. Brain and liver Bdnf mRNA showed a 12-h phase shift when fed ketogenic diet (KD) compared with high-fat diet (HFD) or low-fat diet (LFD). Brain or liver Bdnf mRNA did not show the typical phase advance usually seen under time-restricted feeding (RF). Clock knockdown in HT-4 hippocampal neurons led to 86% up-regulation of Bdnf mRNA, whereas it led to 60% down-regulation in AML-12 hepatocytes. Dietary fat in mice or cultured hepatocytes and hippocampal neurons led to increased Bdnf mRNA expression. At the protein level, HFD increased the ratio of the mature BDNF protein (mBDNF) to its precursor (proBDNF). In the liver, RF under LFD or HFD reduced the mBDNF/proBDNF ratio. In the brain, the two signaling pathways related to BDNF, mTOR and AMPK, showed reduced and increased levels, respectively, under timed HFD. In the liver, the reverse was achieved. In summary, Bdnf expression is mediated by the circadian clock and dietary fat. Although RF does not affect its expression phase, in the brain, when combined with high-fat diet, it leads to a unique metabolic state in which AMPK is activated, mTOR is down-regulated and the levels of mBDNF are high. PMID:27113028

  7. BDNF DNA methylation changes as a biomarker of psychiatric disorders: literature review and open access database analysis.

    Science.gov (United States)

    Zheleznyakova, Galina Y; Cao, Hao; Schiöth, Helgi B

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in nervous system development and function and it is well established that BDNF is involved in the pathogenesis of a wide range of psychiatric disorders. Recently, numerous studies have associated the DNA methylation level of BDNF promoters with certain psychiatric phenotypes. In this review, we summarize data from current literature as well as from our own analysis with respect to the correlation of BDNF methylation changes with psychiatric disorders and address questions about whether DNA methylation related to the BDNF can be useful as biomarker for specific neuropsychiatric disorders. PMID:27267954

  8. Expression and Localization of Brain-Derived Neurotrophic Factor (BDNF) mRNA and Protein in Human Submandibular Gland

    International Nuclear Information System (INIS)

    Brain-derived neurotrophic factor (BDNF) promotes cell survival and differentiation in the central and peripheral nervous systems. Previously, we reported that BDNF is produced by salivary glands under acute immobilization stress in rats. However, expression of BDNF is poorly understood in humans, although salivary gland localization of BDNF in rodents has been demonstrated. In the present study, we investigated the expression and localization of BDNF in the human submandibular gland (HSG) using reverse transcription-polymerase chain reaction, western blot analysis, in situ hybridization (ISH), immunohistochemistry (IHC), and ELISA. BDNF was consistently localized in HSG serous and ductal cells, as detected by ISH and IHC, with reactivity being stronger in serous cells. In addition, immunoreactivity for BDNF was observed in the saliva matrix of ductal cavities. Western blotting detected one significant immunoreactive 14 kDa band in the HSG and saliva. Immunoreactivities for salivary BDNF measured by ELISA in humans were 40.76±4.83 pg/mL and 52.64±8.42 pg/mL, in men and women, respectively. Although salivary BDNF concentrations in females tended to be higher than in males, the concentrations were not significantly different. In conclusion, human salivary BDNF may originate from salivary glands, as the HSG appears to produce BDNF

  9. Intracerebral Administration of BDNF Protects Rat Brain Against Oxidative Stress Induced by Ouabain in an Animal Model of Mania.

    Science.gov (United States)

    Valvassori, Samira S; Arent, Camila O; Steckert, Amanda V; Varela, Roger B; Jornada, Luciano K; Tonin, Paula T; Budni, Josiane; Mariot, Edemilson; Kapczinski, Flávio; Quevedo, João

    2015-08-01

    Several studies have suggested that alterations in brain-derived neurotrophic factor (BDNF) and increased oxidative stress have a central role in bipolar disorder (BD). Intracerebroventricular (ICV) injection of ouabain (OUA) in rats alters oxidative stress parameters and decreases BDNF levels in the brain. In this context, the present study aims to investigate the effects of BDNF ICV administration on BDNF levels and oxidative stress parameters in brains of rats submitted to animal model of mania induced by OUA. Wistar rats received an ICV injection of OUA, artificial cerebrospinal fluid (ACSF), OUA plus BDNF, or ACSF plus BDNF. Locomotor activity and risk-taking behavior in the rats were measured using the open-field test. In addition, we analyzed the BDNF levels and oxidative stress parameters (TBARS, Carbonyl, CAT, SOD, GR, and GPx) in the frontal cortex and hippocampus of rats. The BDNF was unable to reverse the ouabain-induced hyperactivity and risk-taking behavior. Nevertheless, BDNF treatment increased BDNF levels, modulated the antioxidant enzymes, and protected the OUA-induced oxidative damage in the brain of rats. These results suggest that BDNF alteration observed in BD patients may be associated with oxidative damage, both seen in this disorder. PMID:25164569

  10. Study of the profile of the neurotrophin BDNF in new leprosy cases before, during and after multidrug therapy

    Directory of Open Access Journals (Sweden)

    Rosane Dias Costa

    2011-02-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is a neurotrophin involved in the survival of neurons and growth and differentiation of dendrites and axons. The purpose of the present study was to evaluate plasma levels of BDNF of leprosy patients at different stages of multidrug therapy (MDT in comparison with non-infected individuals. Plasma levels of BDNF were measured by ELISA in 30 healthy controls and 37 leprosy patients at diagnosis, during and after MDT. Plasma levels of BDNF tended to be higher in control subjects in comparison with leprosy patients, but this difference does not reach statistical significance. Interestingly, BDNF levels changed following MDT, achieving statistical difference only at the 2nd dose of MDT. These results indicate that BDNF may not be a surrogate marker of leprosy infection and/or related neuropathy. Further research is needed to investigate the meaning of BDNF level changes following leprosy treatment.

  11. Long Non-coding RNA in Neurons: New Players in Early Response to BDNF Stimulation.

    Science.gov (United States)

    Aliperti, Vincenza; Donizetti, Aldo

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin family member that is highly expressed and widely distributed in the brain. BDNF is critical for neural survival and plasticity both during development and in adulthood, and dysfunction in its signaling may contribute to a number of neurodegenerative disorders. Deep understanding of the BDNF-activated molecular cascade may thus help to find new biomarkers and therapeutic targets. One interesting direction is related to the early phase of BDNF-dependent gene expression regulation, which is responsible for the activation of selective gene programs that lead to stable functional and structural remodeling of neurons. Immediate-early coding genes activated by BDNF are under investigation, but the involvement of the non-coding RNAs is largely unexplored, especially the long non-coding RNAs (lncRNAs). lncRNAs are emerging as key regulators that can orchestrate different aspects of nervous system development, homeostasis, and plasticity, making them attractive candidate markers and therapeutic targets for brain diseases. We used microarray technology to identify differentially expressed lncRNAs in the immediate response phase of BDNF stimulation in a neuronal cell model. Our observations on the putative functional role of lncRNAs provide clues to their involvement as master regulators of gene expression cascade triggered by BDNF. PMID:26973456

  12. BDNF polymorphism associates with decline in set shifting in Parkinson's disease.

    Science.gov (United States)

    van der Kolk, Nicolien M; Speelman, Arlene D; van Nimwegen, Marlies; Kessels, Roy P C; IntHout, Joanna; Hakobjan, Marina; Munneke, Marten; Bloem, Bastiaan R; van de Warrenburg, Bart P

    2015-03-01

    Parkinson's disease (PD) is a neurodegenerative disorder caused by nigrostriatal dopaminergic degeneration. Brain-derived neurotrophic factor (BDNF) is a key protein in brain plasticity and is particularly important for survival of dopaminergic neurons. The Val66Met polymorphism of BDNF (rs6265) has been associated with functional differences (mainly cognitive) between healthy adults and also with differences in the clinical expression of several other neuropsychiatric illnesses including PD. However, these studies used different outcome measures, have not been replicated, and were cross sectional, making it difficult to establish the role of BDNF in the clinical variability of PD. Here, a large cohort of 384 PD patients were followed up for 2 years, and associations between BDNF genotype and various clinical characteristics were examined. The BDNF Met-allele carriers showed a significantly smaller decline in set shifting during follow-up compared with the homozygous BDNF Val-allele carriers. Contrary to previous assumptions, these results indicate that mental flexibility is one of the cognitive processes that may benefit from the BDNF Met allele in PD patients. PMID:25444596

  13. Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

    Science.gov (United States)

    Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

    2012-04-01

    The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p LD(50) VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure. PMID:22240983

  14. Fear extinction and BDNF: translating animal models of PTSD to the clinic.

    Science.gov (United States)

    Andero, R; Ressler, K J

    2012-07-01

    Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophin involved in synaptic plasticity processes that are required for long-term learning and memory. Specifically, BDNF gene expression and activation of its high-affinity tropomyosin-related kinase B (TrkB) receptor are necessary in the amygdala, hippocampus and prefrontal cortex for the formation of emotional memories, including fear memories. Among the psychiatric disorders with altered fear processing, there is post-traumatic stress disorder (PTSD) which is characterized by an inability to extinguish fear memories. Since BDNF appears to enhance extinction of fear, targeting impaired extinction in anxiety disorders such as PTSD via BDNF signalling may be an important and novel way to enhance treatment efficacy. The aim of this review is to provide a translational point of view that stems from findings in the BDNF regulation of synaptic plasticity and fear extinction. In addition, there are different systems that seem to alter fear extinction through BDNF modulation like the endocannabinoid system and the hypothalamic-pituitary adrenal axis. Recent work also finds that the pituitary adenylate cyclase-activating polypeptide and PAC1 receptor, which are upstream of BDNF activation, may be implicated in PTSD. Especially interesting are data that exogenous fear extinction enhancers such as antidepressants, histone deacetylases inhibitors and D-cycloserine, a partial N-methyl d-aspartate agonist, may act through or in concert with the BDNF-TrkB system. Finally, we review studies where recombinant BDNF and a putative TrkB agonist, 7,8-dihydroxyflavone, may enhance extinction of fear. These approaches may lead to novel agents that improve extinction in animal models and eventually humans. PMID:22530815

  15. BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals.

    Science.gov (United States)

    Chen, Wenling; Walwyn, Wendy; Ennes, Helena S; Kim, Hyeyoung; McRoberts, James A; Marvizón, Juan Carlos G

    2014-05-01

    NMDA receptors in primary afferent terminals can contribute to hyperalgesia by increasing neurotransmitter release. In rats and mice, we found that the ability of intrathecal NMDA to induce neurokinin 1 receptor (NK1R) internalization (a measure of substance P release) required a previous injection of BDNF. Selective knock-down of NMDA receptors in primary afferents decreased NMDA-induced NK1R internalization, confirming the presynaptic location of these receptors. The effect of BDNF was mediated by tropomyosin-related kinase B (trkB) receptors and not p75 neurotrophin receptors (p75(NTR) ), because it was not produced by proBDNF and was inhibited by the trkB antagonist ANA-12 but not by the p75(NTR) inhibitor TAT-Pep5. These effects are probably mediated through the truncated form of the trkB receptor as there is little expression of full-length trkB in dorsal root ganglion (DRG) neurons. Src family kinase inhibitors blocked the effect of BDNF, suggesting that trkB receptors promote the activation of these NMDA receptors by Src family kinase phosphorylation. Western blots of cultured DRG neurons revealed that BDNF increased Tyr(1472) phosphorylation of the NR2B subunit of the NMDA receptor, known to have a potentiating effect. Patch-clamp recordings showed that BDNF, but not proBDNF, increased NMDA receptor currents in cultured DRG neurons. NMDA-induced NK1R internalization was also enabled in a neuropathic pain model or by activating dorsal horn microglia with lipopolysaccharide. These effects were decreased by a BDNF scavenger, a trkB receptor antagonist and a Src family kinase inhibitor, indicating that BDNF released by microglia potentiates NMDA receptors in primary afferents during neuropathic pain. PMID:24611998

  16. BDNF Methylation and Maternal Brain Activity in a Violence-Related Sample.

    Directory of Open Access Journals (Sweden)

    Dominik A Moser

    Full Text Available It is known that increased circulating glucocorticoids in the wake of excessive, chronic, repetitive stress increases anxiety and impairs Brain-Derived Neurotrophic Factor (BDNF signaling. Recent studies of BDNF gene methylation in relation to maternal care have linked high BDNF methylation levels in the blood of adults to lower quality of received maternal care measured via self-report. Yet the specific mechanisms by which these phenomena occur remain to be established. The present study examines the link between methylation of the BDNF gene promoter region and patterns of neural activity that are associated with maternal response to stressful versus non-stressful child stimuli within a sample that includes mothers with interpersonal violence-related PTSD (IPV-PTSD. 46 mothers underwent fMRI. The contrast of neural activity when watching children-including their own-was then correlated to BDNF methylation. Consistent with the existing literature, the present study found that maternal BDNF methylation was associated with higher levels of maternal anxiety and greater childhood exposure to domestic violence. fMRI results showed a positive correlation of BDNF methylation with maternal brain activity in the anterior cingulate (ACC, and ventromedial prefrontal cortex (vmPFC, regions generally credited with a regulatory function toward brain areas that are generating emotions. Furthermore we found a negative correlation of BDNF methylation with the activity of the right hippocampus. Since our stimuli focus on stressful parenting conditions, these data suggest that the correlation between vmPFC/ACC activity and BDNF methylation may be linked to mothers who are at a disadvantage with respect to emotion regulation when facing stressful parenting situations. Overall, this study provides evidence that epigenetic signatures of stress-related genes can be linked to functional brain regions regulating parenting stress, thus advancing our understanding of

  17. Age-related differences in plasma BDNF levels after prolonged bed rest.

    Science.gov (United States)

    Soavi, Cecilia; Marušič, Uroš; Sanz, Juana Maria; Morieri, Mario Luca; Dalla Nora, Edoardo; Šimunič, Bostjan; Pišot, Rado; Zuliani, Giovanni; Passaro, Angelina

    2016-05-15

    Brain-derived neurotrophic factor (BDNF) is a member of the family of neurotrophins and has been implicated in brain resistance to insults. Murine studies have demonstrated increased hippocampal concentration after acute immobilization and decreased concentration after chronic immobilization. In humans, chronic stress and sedentary lifestyle result in decreased plasma BDNF levels, but there no data exist regarding acute immobilization. The aim of our study was to evaluate age-related responses [comparing 7 younger subjects (age 23 ± 3 yr) and 8 older subjects (age 60 ± 4 yr)] of plasma BDNF before (baseline data collection, BDC) and after 14 days (BR14) of horizontal bed rest (BR). At BDC, BDNF levels were not different between the two groups (P = 0.101), although at BR14, BDNF levels were higher in older subjects (62.02 ± 18.31) than in younger subjects (34.36 ± 15.24 pg/ml) (P = 0.002). A general linear model for repeated measures showed a significant effect of BR on BDNF (P = 0.002). The BDC BDNF levels correlated with fat-free mass in both populations (ALL) (R = 0.628, P = 0.012), (older, R = 0.753, P = 0.031; younger, R = 0.772, P = 0.042), and with total cholesterol in ALL (R = 0.647, P = 0.009) and older study subjects (R = 0.805, P = 0.016). At BR14, BDNF correlated with total cholesterol (R = 0.579, P = 0.024) and age (R = 0.647, P = 0.009) in ALL. With an increase in age, the brain could become naturally less resistant to acute stressors, including the detrimental effects of prolonged bed rest, and thus the increase in BDNF in the older study group might reflect a protective overshooting of the brain to counteract the negative effects in such conditions. PMID:26940658

  18. TOOTH PULP INFLAMMATION INCREASES BDNF EXPRESSION IN RODENT TRIGEMINAL GANGLION NEURONS

    Science.gov (United States)

    Tarsa, Leila; Bałkowiec-Iskra, Ewa; Kratochvil, F. James; Jenkins, Victoria K.; McLean, Anne; Brown, Alexandra; Smith, Julie Ann; Baumgartner, J. Craig; Balkowiec, Agnieszka

    2010-01-01

    Nociceptive pathways with first-order neurons located in the trigeminal ganglion (TG) provide sensory innervation to the head, and are responsible for a number of common chronic pain conditions, including migraines, temporomandibular disorders and trigeminal neuralgias. Many of those conditions are associated with inflammation. Yet, the mechanisms of chronic inflammatory pain remain poorly understood. Our previous studies show that the neurotrophin brain-derived neurotrophic factor (BDNF) is expressed by adult rat TG neurons, and released from cultured newborn rat TG neurons by electrical stimulation and calcitonin gene-related peptide (CGRP), a well-established mediator of trigeminal inflammatory pain. These data suggest that BDNF plays a role in activity-dependent plasticity at first-order trigeminal synapses, including functional changes that take place in trigeminal nociceptive pathways during chronic inflammation. The present study was designed to determine the effects of peripheral inflammation, using tooth pulp inflammation as a model, on regulation of BDNF expression in TG neurons of juvenile rats and mice. Cavities were prepared in right-side maxillary first and second molars of 4-week-old animals, and left open to oral microflora. BDNF expression in right TG was compared with contralateral TG of the same animal, and with right TG of sham-operated controls, 7 and 28 days after cavity preparation. Our ELISA data indicate that exposing the tooth pulp for 28 days, with confirmed inflammation, leads to a significant upregulation of BDNF in the TG ipsilateral to the affected teeth. Double-immunohistochemistry with antibodies against BDNF combined with one of nociceptor markers, CGRP or TRPV1, revealed that BDNF is significantly upregulated in TRPV1-immunoreactive (IR) neurons in both rats and mice, and CGRP-IR neurons in mice, but not rats. Overall, the inflammation-induced upregulation of BDNF is stronger in mice compared to rats. Thus, mouse TG provides a

  19. BDNF and its TrkB receptor in human fracture healing.

    Science.gov (United States)

    Kilian, Olaf; Hartmann, Sonja; Dongowski, Nicole; Karnati, Srikanth; Baumgart-Vogt, Eveline; Härtel, Frauke V; Noll, Thomas; Schnettler, Reinhard; Lips, Katrin Susanne

    2014-09-01

    Fracture healing is a physiological process of repair which proceeds in stages, each characterized by a different predominant tissue in the fracture gap. Matrix reorganization is regulated by cytokines and growth factors. Neurotrophins and their receptors might be of importance to osteoblasts and endothelial cells during fracture healing. The aim of this study was to examine the presence of brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B receptor (TrkB) during human fracture healing. BDNF and TrkB were investigated in samples from human fracture gaps and cultured cells using RT-PCR, Western blot, and immunohistochemistry. Endothelial cells and osteoblastic cell lines demonstrated a cytoplasmic staining pattern of BDNF and TrkB in vitro. At the mRNA level, BDNF and TrkB were expressed in the initial and osteoid formation phase of human fracture healing. In the granulation tissue of fracture gap, both proteins--BDNF and TrkB--are concentrated in endothelial and osteoblastic cells at the margins of woven bone suggesting their involvement in the formation of new vessels. There was no evidence of BDNF or TrkB during fracture healing in chondrocytes of human enchondral tissue. Furthermore, BDNF is absent in mature bone. Taken together, BDNF and TrkB are involved in vessel formation and osteogenic processes during human fracture healing. The detection of BDNF and its TrkB receptor during various stages of the bone formation process in human fracture gap tissue were shown for the first time. The current study reveals that both proteins are up-regulated in human osteoblasts and endothelial cells in fracture healing. PMID:24984919

  20. Defect chemistry and oxygen transport of (La0.6Sr0.4-xMx)(0.99)Co0.2Fe0.8O3-delta, M = Ca (x=0.05, 0.1), Ba (x=0.1, 0.2), Sr Part I: Defect chemistry

    DEFF Research Database (Denmark)

    Dalslet, Bjarke Thomas; Søgaard, Martin; Bouwmeester, Henry J.M.;

    2009-01-01

    This paper is the first part of a two part series, where the effects of varying the A-site dopant on the defect chemistry, the diffusion coefficient and the surface catalytic properties of the materials (La0.6Sr0.4 − xMx)0.99Co0.2Fe0.8O3 − δ, M = Sr, Ca (x = 0.05, 0.1), Ba (x = 0.1, 0.2) (LSMFC......) have been investigated. In part I, the findings on the defect chemistry are reported, while the transport properties are reported in part II. Substitution of Sr2+ ions with Ca2+ ions (smaller ionic radius) and Ba2+ ions (larger ionic radius) strains the crystal structure differently for each...... oxygen loss was modelled with point defect chemistry models. Measurements at very low pO2 showed several phase transitions....

  1. Transport

    International Nuclear Information System (INIS)

    Transport is one of the major causes of environmental damage in Austria. Energy consumption, pollutants emissions, noise emissions, use of surfaces, sealing of surfaces, dissection of ecosystems and impact on landscape are the most significant environmental impacts caused by it. An overview of the transport development of passengers and freight in Austria is presented. Especially the energy consumption growth, carbon dioxide and nitrogen oxide emissions by type of transport, and the emissions development (HC, particle and carbon monoxide) of goods and passengers transport are analyzed covering the years 1980 - 1999. The health cost resulting from transport-related air pollution in Austria is given and measures to be taken for an effective control of the transport sector are mentioned. Figs. 8, Table 1. (nevyjel)

  2. Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF in mouse ovaries: relationship to oocytes developmental potential.

    Directory of Open Access Journals (Sweden)

    Li-Min Wu

    Full Text Available BACKGROUND: Brain-derived neurotropic factor (BDNF was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. METHODS: Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. RESULTS: Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn't affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. CONCLUSION: BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress.

  3. The role of brain-derived neurotrophic factor (BDNF) in the development of neurogenic detrusor overactivity (NDO).

    Science.gov (United States)

    Frias, Bárbara; Santos, João; Morgado, Marlene; Sousa, Mónica Mendes; Gray, Susannah M Y; McCloskey, Karen D; Allen, Shelley; Cruz, Francisco; Cruz, Célia Duarte

    2015-02-01

    Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients. PMID:25653370

  4. Recombinant AAV-mediated Expression of Human BDNF Protects Neurons against Cell Apoptosis in Aβ-induced Neuronal Damage Model

    Institute of Scientific and Technical Information of China (English)

    LIU Zhaohui; MA Dongliang; FENG Gaifeng; MA Yanbing; HU Haitao

    2007-01-01

    The human brain-derived neurotrophic factor (hBDNF) gene was cloned by polymerase chain reaction and the recombinant adeno-associated viral vector inserted with hBDNF gene (AAV-hBDNF) was constructed. Cultured rat hippocampal neurons were treated with Aβ25-35 and serued as the experimental Aβ-induced neuronal damage model (AD model), and the AD model was infected with AAV-hBDNF to explore neuroprotective effects of expression of BDNF. Cell viability was assayed by MTT. The expression of bcl-2 anti-apoptosis protein was detected by immunocytochemical staining. The change of intracellular free Ca ion ([Ca2+]i) was measured by laser scanning confocal microscopy. The results showed that BDNF had protective effects against Aβ-induced neuronal damage. The expression of the bcl-2 anti-apoptosis protein was raised significantly and the balance of [Ca2+]i was maintained in the AAV-hBDNF treatment group as compared with AD model group. These data suggested that recombinant AAV mediated a stable expression of hBDNF in cultured hippocampal neurons and resulted in significant neuron protective effects in AD model. The BDNF may reduce neuron apoptosis through increasing the expression of the bcl-2 anti-apoptosis protein and inhibiting intracellular calcium overload. The viral vector-mediated gene expression of BDNF may pave the way of a novel therapeutic strategy for the treatment of neurodegenerative diseases such as Alzheimer's disease.

  5. Systemic delivery of recombinant brain derived neurotrophic factor (BDNF in the R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Carmela Giampà

    Full Text Available Loss of huntingtin-mediated BDNF gene transcription has been shown to occur in HD and thus contribute to the degeneration of the striatum. Several studies have indicated that an increase in BDNF levels is associated with neuroprotection and amelioration of neurological signs in animal models of HD. In a recent study, an increase in BDNF mRNA and protein levels was recorded in mice administered recombinant BDNF peripherally. Chronic, indwelling osmotic mini-pumps containing either recombinant BDNF or saline were surgically placed in R6/2 or wild-type mice from 4 weeks of age until euthanasia. Neurological evaluation (paw clasping, rotarod performance, locomotor activity in an open field was performed. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that BDNF- treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as brain volume, striatal atrophy, size and morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. BDNF was effective in increasing significantly the levels of activated CREB and of BDNF the striatal spiny neurons. Moreover, systemically administered BDNF increased the synthesis of BDNF as demonstrated by RT-PCR, and this might account for the beneficial effects observed in this model.

  6. The role of BDNF in depression on the basis of its location in the neural circuitry

    Institute of Scientific and Technical Information of China (English)

    Hui YU; Zhe-yu CHEN

    2011-01-01

    Depression is one of the most prevalent and life-threatening forms of mental illnesses and the neural circuitry underlying depression remains incompletely understood. Most attention in the field has focused on hippocampal and frontal cortical regions for their roles in depression and antidepressant action. While these regions no doubt play important roles in the mental illness, there is compelling evi-dence that other brain regions are also involved. Brain-derived neurotrophic factor (BDNF) is broadly expressed in the developing and adult mammalian brain and has been implicated in development, neural regeneration, synaptic transmission, synaptic plasticity and neurogenesis. Recently BDNF has been shown to play an important role in the pathophysiology of depression, however there are con-troversial reports about the effects of BDNF on depression. Here, we present an overview of the current knowledge concerning BDNF actions and associated intracellular signaling in hippocampus, prefrontal cortex, nucleus accumbens (NAc) and amygdala as their rela-tion to depression.

  7. BDNF is a novel marker of cognitive function in ageing women: the DR's EXTRA Study

    DEFF Research Database (Denmark)

    Komulainen, P.; Pedersen, Maria; Hanninen, T.;

    2008-01-01

    Brain-derived neurotrophic factor (BDNF) is one of the key molecules modulating brain plasticity. While low circulating levels of BDNF have been suggested to predispose to Alzheimer's disease, very little data are available on its association with cognitive function in general population. We...... evaluated the association between plasma BDNF levels and cognition in a representative population sample of ageing men and women. The subjects (n=1389) were participants of the Dose-Responses to Exercise Training (DR's EXTRA) Study and represent a random sample of Eastern Finnish people (684 men and 705...... women), 57-79 years of age at baseline of the study. Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). Cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery. Women had a higher mean...

  8. Fear extinction and BDNF: Translating animal models of PTSD to the clinic

    OpenAIRE

    Andero, Raül; Ressler, Kerry J.

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophin involved in synaptic plasticity processes that are required for long-term learning and memory. Specifically, BDNF gene expression and activation of its high-affinity TrkB receptor are necessary in the amygdala, hippocampus and prefrontal cortex for the formation of emotional memories, including fear memories. Among the psychiatric disorders with altered fear processing there is Post-traumatic Stress Disorder (PTSD) whic...

  9. Effects of the BDNF Val66Met Polymorphism on White Matter Microstructure in Healthy Adults

    OpenAIRE

    Tost, Heike; Alam, Tajvar; Geramita, Matthew; Rebsch, Christine; Kolachana, Bhaskar; Dickinson, Dwight; Verchinski, Beth A.; Lemaitre, Herve; Barnett, Alan S.; Trampush, Joey W.; Weinberger, Daniel R.; Marenco, Stefano

    2012-01-01

    The BDNF Val66Met polymorphism, a possible risk variant for mental disorders, is a potent modulator of neural plasticity in humans and has been linked to deficits in gray matter structure, function, and cognition. The impact of the variant on brain white matter structure, however, is controversial and remains poorly understood. Here, we used diffusion tensor imaging to examine the effects of BDNF Val66Met genotype on white matter microstructure in a sample of 85 healthy Caucasian adults. We d...

  10. BDNF deficiency and young-adult methamphetamine induce sex-specific effects on prepulse inhibition regulation

    Directory of Open Access Journals (Sweden)

    Elizabeth E Manning

    2013-06-01

    Full Text Available Brain-derived neurotrophic factor (BDNF has been implicated in the pathophysiology of schizophrenia, yet its role in the development of specific symptoms is unclear. Methamphetamine (METH users have an increased risk of psychosis and schizophrenia, and METH-treated animals have been used extensively as a model to study the positive symptoms of schizophrenia. We investigated whether METH treatment in BDNF heterozygous mutant mice (HET has cumulative effects on sensorimotor gating, including the disruptive effects of psychotropic drugs. BDNF HETs and WT littermates were treated during young-adulthood with METH and, following a two-week break, prepulse inhibition (PPI was examined. At baseline, BDNF HETs showed reduced PPI compared to WT mice irrespective of METH pre-treatment. An acute challenge with amphetamine (AMPH disrupted PPI but male BDNF HETs were more sensitive to this effect, irrespective of METH pre-treatment. In contrast, female mice treated with METH were less sensitive to the disruptive effects of AMPH, and there were no effects of BDNF genotype. Similar changes were not observed in the response to an acute apomorphine or MK-801 challenge. These results show that genetically-induced reduction of BDNF caused changes in a behavioural endophenotype relevant to the positive symptoms of schizophrenia. However, major sex differences were observed in the effects of a psychotropic drug challenge on this behaviour. These findings suggest sex differences in the effects of BDNF depletion and METH treatment on the monoamine signaling pathways that regulate PPI. Given that these same pathways are thought to contribute to the expression of positive symptoms in schizophrenia, this work suggests that there may be significant sex differences in the pathophysiology underlying these symptoms. Elucidating these sex differences may be important for our understanding of the neurobiology of schizophrenia and developing better treatments strategies for the

  11. The role of brain-derived neurotropic factor (BDNF) in stress-related brain disorders

    OpenAIRE

    Giese, Maria

    2013-01-01

    Evidence has been raised demonstrating the complex outcome of stress on the BDNF system and that the protein is a critical backbone in the functioning and well-being of the central nervous system. Several studies support the “neurotrophin hypothesis of depression”, which postulates that reduced brain levels of BDNF could contribute to atrophy and cell loss as observed in the hippocampus of depressed subjects. However, the precise mechanism underlying this down-regulation has not been fully un...

  12. Effect of voluntary exercise on BDNF/TrkB gene expression and alcohol intake.

    OpenAIRE

    Jonsson, Josefine

    2012-01-01

    Voluntary wheel running is rewarding and believed to activate the same brain reward system as in alcohol and drug addiction. Brain-derived neurotrophic factor (BDNF), a well-known growth factor widely expressed in the brain, is modulated by both voluntary exercise and alcohol consumption. The aim of this study was to evaluate how voluntary exercise affects the expression levels of BDNF and its receptor TrkB in brain regions involved in positive and negative reinforcement. Additionally we want...

  13. BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals

    OpenAIRE

    Chen, Wenling; Walwyn, Wendy; Ennes, Helena S.; Kim, Hyeyoung; McRoberts, James A.; Marvizón, Juan Carlos G.

    2014-01-01

    NMDA receptors in primary afferent terminals can contribute to hyperalgesia by increasing neurotransmitter release. In rats and mice, we found that the ability of intrathecal NMDA to induce neurokinin 1 receptor (NK1R) internalization (a measure of substance P release) required a previous injection of BDNF. Selective knock-down of NMDA receptors in primary afferents decreased NMDA-induced NK1R internalization, confirming the presynaptic location of these receptors. The effect of BDNF was medi...

  14. Comparative Effect of Treadmill Exercise on Mature BDNF Production in Control versus Stroke Rats

    OpenAIRE

    Quirié, Aurore; Hervieu, Marie; Garnier, Philippe; Demougeot, Céline; Mossiat, Claude; Bertrand, Nathalie; Martin, Alain; Marie, Christine; Prigent-Tessier, Anne

    2012-01-01

    Physical exercise constitutes an innovative strategy to treat deficits associated with stroke through the promotion of BDNF-dependent neuroplasticity. However, there is no consensus on the optimal intensity/duration of exercise. In addition, whether previous stroke changes the effect of exercise on the brain is not known. Therefore, the present study compared the effects of a clinically-relevant form of exercise on cerebral BDNF levels and localization in control versus stroke rats. For this ...

  15. A Longitudinal Study of BDNF Promoter Methylation and Depression in Breast Cancer

    OpenAIRE

    Kang, Hee-Ju; Kim, Jae-Min; Kim, Seon-Young; Kim, Sung-Wan; Shin, Il-Seon; Kim, Hye-Ran; Park, Min-Ho; Shin, Myung-Geun; Yoon, Jung-Han; Yoon, Jin-Sang

    2015-01-01

    Objective Brain-derived neurotrophic factor (BDNF) is investigated in depression related to medical disorders and its secretion is influenced by epigenetic factors. We investigated the association between BDNF promoter methylation and depression following mastectomy for breast cancer. Methods In total, 309 patients with breast cancer were evaluated 1 week after mastectomy, and 244 (79%) were followed up 1 year later. Depression was diagnosed (major or minor depressive disorder) according to D...

  16. Selective DNA Methylation of BDNF Promoter in Bipolar Disorder: Differences Among Patients with BDI and BDII

    OpenAIRE

    D'Addario, Claudio; Dell'Osso, Bernardo; Palazzo, Maria Carlotta; Benatti, Beatrice; Lietti, Licia; Cattaneo, Elisabetta; Galimberti, Daniela; Fenoglio, Chiara; Cortini, Francesca; Scarpini, Elio; Arosio, Beatrice; Di Francesco, Andrea; Di Benedetto, Manuela; Romualdi, Patrizia; Candeletti, Sanzio

    2012-01-01

    The etiology of bipolar disorder (BD) is still poorly understood, involving genetic and epigenetic mechanisms as well as environmental contributions. This study aimed to investigate the degree of DNA methylation at the promoter region of the brain-derived neurotrophic factor (BDNF) gene, as one of the candidate genes associated with major psychoses, in peripheral blood mononuclear cells isolated from 94 patients with BD (BD I=49, BD II=45) and 52 healthy controls. A significant BDNF gene expr...

  17. BDNF mediates improvements in executive function following a 1-year exercise intervention

    OpenAIRE

    Regina Lynn Leckie; Oberlin, Lauren E.; Voss, Michelle W.; Prakash, Ruchika S.; Amanda eSzabo-Reed; Laura eChaddock-Heyman; Phillips, Siobhan M.; Gothe, Neha P.; Emily eMailey; Victoria Jeanne Vieira-Potter; Martin, Stephen A.; Pence, Brandt D.; Mingkuan eLin; Raja eParasuraman; Greenwood, Pamela M.

    2014-01-01

    Executive function declines with age, but engaging in aerobic exercise may attenuate decline. One mechanism by which aerobic exercise may preserve executive function is through the up-regulation of brain-derived neurotropic factor (BDNF), which also declines with age. The present study examined BDNF as a mediator of the effects of a 1-year walking intervention on executive function in 90 older adults (mean age = 66.82). Participants were randomized to a stretching and toning control group or ...

  18. BDNF Plasma Level als Marker für Alzheimer in der VITA Studie

    OpenAIRE

    Altides, Anastasia Elisabeth

    2011-01-01

    HINTERGRUND: Der brain-derived neurotrophic factor (BDNF) reguliert die synaptische Plastizität und spielt somit eine wichtige Rolle in der Gedächtnisbildung und -erhaltung. Deswegen gibt es eingehende Untersuchungen dieses neurotrophischen Faktors in Bezug auf Demenzerkrankungen, vor allem der Alzheimer Demenz. In dieser Studie wurde nach einem Zusammenhang zwischen BDNF Blutplasmawerten und der Alzheimer Demenz in einer longitudinalen Kohortenstudie, der Vienna-Transdanube-Aging(VITA)-Studi...

  19. The effects of vortex localization at columnar defects on the mixed state transport properties of Tl2Ba2CaCu2O8 films

    International Nuclear Information System (INIS)

    The effects of vortex localization at columnar defects on the linear and non-linear dissipation in Tl2Ba2CaCu2O8 films are studied. The confinement of vortices into columnar defects leads to a minimum in the angular dependence of linear resistivity when the external field is brought into alignment with the defects. This observation provides compelling evidence for non-zero line tension of vortices in this highly anisotropic cuprate. The electric field vs current density (E-J) isotherms, and the temperature dependence of linear resistivity, both, indicate a Bose glass type of phase transition in this system

  20. Serum cortisol and BDNF in patients with major depression-effect of yoga.

    Science.gov (United States)

    Naveen, G H; Varambally, Shivarama; Thirthalli, Jagadisha; Rao, Mukund; Christopher, Rita; Gangadhar, B N

    2016-06-01

    Depression is associated with low serum Brain Derived Neurotrophic Factor (BDNF) and elevated levels of serum cortisol. Yoga practices have been associated with antidepressant effects, increase in serum BDNF, and reduction in serum cortisol. This study examined the association between serum BDNF and cortisol levels in drug-naïve patients with depression treated with antidepressants, yoga therapy, and both. Fifty-four drug-naïve consenting adult outpatients with Major Depression (32 males) received antidepressants only (n = 16), yoga therapy only (n = 19), or yoga with antidepressants (n = 19). Serum BDNF andcortisol levels were obtained before and after 3 months using a sandwich ELISA method. One-way ANOVA, Chi-square test, and Pearson's correlation tests were used for analysis. The groups were comparable at baseline on most parameters. Significant improvement in depression scores and serum BDNF levels, and reduction in serum cortisol in the yoga groups, have been described in previous reports. A significant negative correlation was observed between change in BDNF (pre-post) and cortisol (pre-post) levels in the yoga-only group (r = -0.59, p = 0.008). In conclusion, yoga may facilitate neuroplasticity through stress reduction in depressed patients. Further studies are needed to confirm the findings and delineate the pathways for these effects. PMID:27174729

  1. Effect of Mozart Music on Hippocampal Content of BDNF in Postnatal Rats

    Directory of Open Access Journals (Sweden)

    Mohsen Marzban

    2011-04-01

    Full Text Available Introduction: It has shown that listening to Mozart music can potentiate spatial tasks in human; and reduce seizure attacks in epileptic patients. A few studies have reported the effects of prenatal plus postpartum exposure of mice to the Mozart music on brain-drived neurotrophic factor (BDNF in the hippocampus. Here we investigated the effect of postpartum exposure to The Mozart music on BDNF concentration in the hippocampus of rat.Methods: Thirty male one day old newborn Wistar rats divided randomly in two equal experimental and control groups. Experimental group exposed to slow rhythm Mozart music (Mozart Sonata for two pianos KV 448, 6 hour per day; sound pressure levels, between 80 and 100 dB for 60 successive days. The control group was kept in separate room with housing conditions like experimental group except music exposure. After 60 days the rats were euthanized and hippocampuses extracted; then the content of BDNF protein was measured using ELISA sandwich method. Results: Data analysis revealed that rats exposed to Mozart Sonata music had significantly increased BDNF content in the hippocampus as compared to control rats (P±0.01. The concentrations of BDNF were 86.30±2.26 and 94.60 ±6.22 ng/g wet weight in control and music exposure groups respectively.Discussion: Exposure to the Mozart music early in life can increase the BDNF concentration in the hippocampus in rats.

  2. BDNF gene polymorphisms and haplotypes in relation to cognitive performance in Polish healthy subjects.

    Science.gov (United States)

    Wiłkość, Monika; Szałkowska, Agnieszka; Skibińska, Maria; Zając-Lamparska, Ludmiła; Maciukiewicz, Małgorzata; Araszkiewicz, Aleksander

    2016-01-01

    The brain derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in the cell survival, axonal and dendritic growth, and synaptic plasticity. BDNF gene polymorphisms, 'functional Val66Met mainly, were shown to influence human brain structure and cognition. The aim of the study was to assess the relationship between twelve BDNF gene variants and their haplotypes and cognitive performance measured using the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT), the Stroop Test which are to a large extent connected with prefrontal cortex activity. Our sample consisted of 460 healthy participants from Polish population. We detected possible association between five BDNF polymorphisms (rs11030101, rs10835210, rs2049046, rs2030324, rs2883187) and TMT_A. Additionally, one haplotype block made from eleven BDNF variants (rs2883187, rs1401635, rs2049046, rs2030324, rs11030101, rs10835210, rs1013402, rs1401635, rs1013402), as significant linkage disequilibrium appeared. We discovered possible relationships of CACCGCGTACG and CACCGCGTACG haplotypes with TMT_A and TMT_B performance respectively. Our results confirmed the involvement of BDNF in the regulation of psychomotor speed, working memory and executive function in healthy subjects measured by a task engaging visuoperceptual abilities. PMID:27102917

  3. Role of Stress-Related Brain-Derived Neurotrophic Factor (BDNF) in the Rat Submandibular Gland

    International Nuclear Information System (INIS)

    The nerve growth factor (NGF) family comprises NGF, brain-derived neurotrophic factor (BDNF) and neurotrophins (NTs)-3, -4/5, -6 and -7, all of which are collectively referred to as neurotrophins. However, the expression of neurotrophins other than NGF in the salivary gland has not been described in detail. Through interaction with the TrkB receptor, BDNF plays an important role in long-term potentiation. We found that BDNF expression increased within submandibular gland tissue in response to stress, suggesting that the salivary glands are sensitive to stress. In addition, stress caused increases in plasma BDNF derived from the submandibular gland and in TrkB receptor mRNA in the adrenal medulla. Plasma BDNF might activate TrkB receptors in the adrenal medulla during acute stress. The salivary glands are likely to influence not only oral health, but also systemic organs. This review addressed the relationship between hormone-like effects and stress-related BDNF expression in the rat submandibular gland

  4. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males.

    Science.gov (United States)

    Griffin, Éadaoin W; Mullally, Sinéad; Foley, Carole; Warmington, Stuart A; O'Mara, Shane M; Kelly, Aine M

    2011-10-24

    Physical activity has been reported to improve cognitive function in humans and rodents, possibly via a brain-derived neurotrophic factor (BDNF)-regulated mechanism. In this study of human subjects, we have assessed the effects of acute and chronic exercise on performance of a face-name matching task, which recruits the hippocampus and associated structures of the medial temporal lobe, and the Stroop word-colour task, which does not, and have assessed circulating concentrations of BDNF and IGF-1 in parallel. The results show that a short period of high-intensity cycling results in enhancements in performance of the face-name matching, but not the Stroop, task. These changes in cognitive function were paralleled by increased concentration of BDNF, but not IGF-1, in the serum of exercising subjects. 3 weeks of cycling training had no effect on cardiovascular fitness, as assessed by VO2 scores, cognitive function, or serum BDNF concentration. Increases in fitness, cognitive function and serum BDNF response to acute exercise were observed following 5 weeks of aerobic training. These data indicate that both acute and chronic exercise improve medial temporal lobe function concomitant with increased concentrations of BDNF in the serum, suggesting a possible functional role for this neurotrophic factor in exercise-induced cognitive enhancement in humans. PMID:21722657

  5. A significant association between BDNF promoter methylation and the risk of drug addiction.

    Science.gov (United States)

    Xu, Xuting; Ji, Huihui; Liu, Guili; Wang, Qinwen; Liu, Huifen; Shen, Wenwen; Li, Longhui; Xie, Xiaohu; Zhou, Wenhua; Duan, Shiwei

    2016-06-10

    As a member of the neurotrophic factor family, brain derived neurotrophic factor (BDNF) plays an important role in the survival and differentiation of neurons. The aim of our work was to evaluate the role of BDNF promoter methylation in drug addiction. A total of 60 drug abusers (30 heroin and 30 methylamphetamine addicts) and 52 healthy age- and gender-matched controls were recruited for the current case control study. Bisulfite pyrosequencing technology was used to determine the methylation levels of five CpGs (CpG1-5) on the BDNF promoter. Among the five CpGs, CpG5 methylation was significantly lower in drug abusers than controls. Moreover, significant associations were found between CpG5 methylation and addictive phenotypes including tension-anxiety, anger-hostility, fatigue-inertia, and depression-dejection. In addition, luciferase assay showed that the DNA fragment of BDNF promoter played a key role in the regulation of gene expression. Our results suggest that BDNF promoter methylation is associated with drug addiction, although further studies are needed to understand the mechanisms by which BDNF promoter methylation contributes to the pathophysiology of drug addiction. PMID:26976342

  6. The defect

    CERN Document Server

    Kuhlmann, Franz-Viktor

    2010-01-01

    We give an introduction to the valuation theoretical phenomenon of "defect", also known as "ramification deficiency". We describe the role it plays in deep open problems in positive characteristic: local uniformization (the local form of resolution of singularities), the model theory of valued fields, the structure theory of valued function fields. We give several examples of algebraic extensions with non-trivial defect. We indicate why Artin-Schreier defect extensions play a central role and describe a way to classify them. Further, we give an overview of various results about the defect that help to tame or avoid it, in particular "stability" theorems and theorems on "henselian rationality", and show how they are applied. Finally, we include a list of open problems.

  7. Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats

    OpenAIRE

    M’Dahoma, Saïd; Barthélemy, Sandrine; Tromilin, Claire; Jeanson, Tiffany; Viguier, Florent; Michot, Benoit; Pezet, Sophie; Hamon, Michel; Bourgoin, Sylvie

    2015-01-01

    International audience Numerous reported data support the idea that Brain Derived Neurotrophic Factor (BDNF) is critically involved in both depression and comorbid pain. The possible direct effect of BDNF on pain mechanisms was assessed here and compared with behavioral/neurobiological features of neuropathic pain caused by chronic constriction injury to the sciatic nerve (CCI-SN). Sprague–Dawley male rats were either injected intrathecally with BDNF (3.0 ng i.t.) or subjected to unilatera...

  8. Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats.

    Science.gov (United States)

    M'Dahoma, Saïd; Barthélemy, Sandrine; Tromilin, Claire; Jeanson, Tiffany; Viguier, Florent; Michot, Benoit; Pezet, Sophie; Hamon, Michel; Bourgoin, Sylvie

    2015-11-01

    Numerous reported data support the idea that Brain Derived Neurotrophic Factor (BDNF) is critically involved in both depression and comorbid pain. The possible direct effect of BDNF on pain mechanisms was assessed here and compared with behavioral/neurobiological features of neuropathic pain caused by chronic constriction injury to the sciatic nerve (CCI-SN). Sprague-Dawley male rats were either injected intrathecally with BDNF (3.0 ng i.t.) or subjected to unilateral CCI-SN. Their respective responses to anti-hyperalgesic drugs were assessed using the Randall-Selitto test and both immunohistochemical and RT-qPCR approaches were used to investigate molecular/cellular mechanisms underlying hyperalgesia in both models. Long lasting hyperalgesia and allodynia were induced by i.t. BDNF in intact healthy rats like those found after CCI-SN. Acute treatment with the BDNF-TrkB receptor antagonist cyclotraxin B completely prevented i.t. BDNF-induced hyperalgesia and partially reversed this symptom in both BDNF-pretreated and CCI-SN lesioned rats. Acute administration of the anticonvulsant pregabalin, the NMDA receptor antagonist ketamine, the opioid analgesics morphine and tapentadol or the antidepressant agomelatine also transiently reversed hyperalgesia in both i.t. BDNF injected- and CCI-SN lesioned-rats. Marked induction of microglia activation markers (OX42, Iba1, P-p38), proinflammatory cytokine IL-6, NMDA receptor subunit NR2B and BDNF was found in spinal cord and/or dorsal root ganglia of CCI-SN rats. A long lasting spinal BDNF overexpression was also observed in BDNF i.t. rats, indicating an autocrine self-induction, with downstream long lasting TrkB-mediated neuropathic-like pain. Accordingly, TrkB blockade appeared as a relevant approach to alleviate not only i.t. BDNF- but also nerve lesion-evoked neuropathic pain. PMID:26343858

  9. Neurochemical properties of BDNF-containing neurons projecting to rostral ventromedial medulla in the ventrolateral periaqueductal gray

    OpenAIRE

    Yin, Jun-Bin; Wu, Huang-Hui; Dong, Yu-Lin; Zhang, Ting; Wang, Jian; Zhang, Yong; Wei, Yan-Yan; Lu, Ya-Cheng; Wu, Sheng-Xi; WANG, Wen; Li, Yun-Qing

    2014-01-01

    The periaqueductal gray (PAG) modulates nociception via a descending pathway that relays in the rostral ventromedial medulla (RVM) and terminates in the spinal cord. Previous behavioral pharmacology and electrophysiological evidence suggests that brain-derived neurotrophic factor (BDNF) plays an important role in descending pain modulation, likely through the PAG-RVM pathway. However, detailed information is still lacking on the distribution of BDNF, activation of BDNF-containing neurons proj...

  10. Targeted Disruption of the BDNF Gene Perturbs Brain and Sensory Neuron Development but Not Motor Neuron Development

    OpenAIRE

    Jones, Kevin R; Fariñas, Isabel; Backus, Carey; Reichardt, Louis F.

    1994-01-01

    Brain-derived neurotrophic factor (BDNF), a neurotrophin, enhances the survival and differentiation of several classes of neurons in vitro. To determine its essential functions, we have mutated the BDNF gene. Most homoxygote mutants die within 2 days after birth, but a fraction live for 2–4 weeks. These develop symptoms of nervous system dysfunction, including ataxia. The BDNF mutant homoxygotes have substantlaliy reduced numbers of cranlal and spinal sensory neurons. Although their central n...

  11. Cognitive dysfunction and epigenetic alterations of the BDNF gene are induced by social isolation during early adolescence.

    Science.gov (United States)

    Li, Man; Du, Wei; Shao, Feng; Wang, Weiwen

    2016-10-15

    Early life adversity, such as social isolation, causes a variety of changes to the development of cognitive abilities and the nervous system. Increasing evidence has shown that epigenetic modifications mediate gene-environment interactions throughout the lifespan. In this study, we investigated the effect of adolescent social isolation on cognitive behaviours and epigenetic alterations of the brain-derived neurotrophic factor (BDNF) gene. Male Sprague Dawley rats were randomly assigned to either group-reared or isolation-reared conditions during post-natal days (PNDs) 21-34. On PND 56, all rats underwent behavioural testing and were then sacrificed for biochemical testing. Adolescent social isolation induced impaired PPI. Regarding BDNF, the isolation-reared rats demonstrated increased BDNF mRNA levels, H3 acetylation at the BDNF gene and BDNF protein expression in the medial prefrontal cortex (mPFC). In contrast, the BDNF mRNA levels, H3 acetylation of the BDNF gene and BDNF protein expression were decreased in the hippocampus of the isolation-reared rats. The present study indicated that epigenetic regulation of BDNF may be one of the molecular mechanisms that mediated the cognitive dysfunction. Moreover, the interaction between the mPFC and hippocampus might play an important role in the regulation of cognitive behaviour. PMID:27435421

  12. Effects of Ethanol on the Expression Level of Various BDNF mRNA Isoforms and Their Encoded Protein in the Hippocampus of Adult and Embryonic Rats

    Directory of Open Access Journals (Sweden)

    Shahla Shojaei

    2015-12-01

    Full Text Available We aimed to compare the effects of oral ethanol (Eth alone or combined with the phytoestrogen resveratrol (Rsv on the expression of various brain-derived neurotrophic factor (BDNF transcripts and the encoded protein pro-BDNF in the hippocampus of pregnant and embryonic rats. A low (0.25 g/kg body weight (BW/day dose of Eth produced an increase in the expression of BDNF exons I, III and IV and a decrease in that of the exon IX in embryos, but failed to affect BDNF transcript and pro-BDNF protein expression in adults. However, co-administration of Eth 0.25 g/kg·BW/day and Rsv led to increased expression of BDNF exons I, III and IV and to a small but significant increase in the level of pro-BDNF protein in maternal rats. A high (2.5 g/kg·BW/day dose of Eth increased the expression of BDNF exons III and IV in embryos, but it decreased the expression of exon IX containing BDNF mRNAs in the maternal rats. While the high dose of Eth alone reduced the level of pro-BDNF in adults, it failed to change the levels of pro-BDNF in embryos. Eth differentially affects the expression pattern of BDNF transcripts and levels of pro-BDNF in the hippocampus of both adult and embryonic rats.

  13. Epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression.

    Science.gov (United States)

    Su, Chun-Lin; Su, Chun-Wei; Hsiao, Ya-Hsin; Gean, Po-Wu

    2016-05-01

    Major depressive disorder (MDD), one of the most common mental disorders, is a significant risk factor for suicide and causes a low quality of life for many people. However, the causes and underlying mechanism of depression remain elusive. In the current work, we investigated epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression. Mice were exposed to inescapable stress and divided into learned helplessness (LH) and resilient (LH-R) groups depending on the number they failed to escape. We found that the LH group had longer immobility duration in the forced swimming test (FST) and tail suspension tests (TST), which is consistent with a depression-related phenotype. Western blotting analysis and enzyme-linked immunosorbent assay (ELISA) revealed that the LH group had lower BDNF expression than that of the LH-R group. The LH group consistently had lower BDNF mRNA levels, as detected by qPCR assay. In addition, we found BDNF exon IV was down-regulated in the LH group. Intraperitoneal injection of imipramine or histone deacetylase inhibitors (HDACi) to the LH mice for 14 consecutive days ameliorated depression-like behaviors and reversed the decrease in BDNF. The expression of HDAC5 was up-regulated in the LH mice, and a ChIP assay revealed that the level of HDAC5 binding to the promoter region of BDNF exon IV was higher than that seen in other groups. Knockdown of HDAC5 reduced depression-like behaviors in the LH mice. Taken together, these results suggest that epigenetic regulation of BDNF by HDAC5 plays an important role in the learned helplessness model of depression. PMID:26921875

  14. Down-regulation of BDNF in cell and animal models increases striatal-enriched protein tyrosine phosphatase 61 (STEP61 ) levels.

    Science.gov (United States)

    Xu, Jian; Kurup, Pradeep; Azkona, Garikoitz; Baguley, Tyler D; Saavedra, Ana; Nairn, Angus C; Ellman, Jonathan A; Pérez-Navarro, Esther; Lombroso, Paul J

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates synaptic strengthening and memory consolidation, and altered BDNF expression is implicated in a number of neuropsychiatric and neurodegenerative disorders. BDNF potentiates N-methyl-D-aspartate receptor function through activation of Fyn and ERK1/2. STriatal-Enriched protein tyrosine Phosphatase (STEP) is also implicated in many of the same disorders as BDNF but, in contrast to BDNF, STEP opposes the development of synaptic strengthening. STEP-mediated dephosphorylation of the NMDA receptor subunit GluN2B promotes internalization of GluN2B-containing NMDA receptors, while dephosphorylation of the kinases Fyn, Pyk2, and ERK1/2 leads to their inactivation. Thus, STEP and BDNF have opposing functions. In this study, we demonstrate that manipulation of BDNF expression has a reciprocal effect on STEP61 levels. Reduced BDNF signaling leads to elevation of STEP61 both in BDNF(+/-) mice and after acute BDNF knockdown in cortical cultures. Moreover, a newly identified STEP inhibitor reverses the biochemical and motor abnormalities in BDNF(+/-) mice. In contrast, increased BDNF signaling upon treatment with a tropomyosin receptor kinase B agonist results in degradation of STEP61 and a subsequent increase in the tyrosine phosphorylation of STEP substrates in cultured neurons and in mouse frontal cortex. These findings indicate that BDNF-tropomyosin receptor kinase B signaling leads to degradation of STEP61 , while decreased BDNF expression results in increased STEP61 activity. A better understanding of the opposing interaction between STEP and BDNF in normal cognitive functions and in neuropsychiatric disorders will hopefully lead to better therapeutic strategies. Altered expression of BDNF and STEP61 has been implicated in several neurological disorders. BDNF and STEP61 are known to regulate synaptic strengthening, but in opposite directions. Here, we report that reduced BDNF signaling leads to elevation of STEP61 both in

  15. BDNF over-expression increases olfactory bulb granule cell dendritic spine density in vivo.

    Science.gov (United States)

    McDole, B; Isgor, C; Pare, C; Guthrie, K

    2015-09-24

    Olfactory bulb granule cells (GCs) are axon-less, inhibitory interneurons that regulate the activity of the excitatory output neurons, the mitral and tufted cells, through reciprocal dendrodendritic synapses located on GC spines. These contacts are established in the distal apical dendritic compartment, while GC basal dendrites and more proximal apical segments bear spines that receive glutamatergic inputs from the olfactory cortices. This synaptic connectivity is vital to olfactory circuit function and is remodeled during development, and in response to changes in sensory activity and lifelong GC neurogenesis. Manipulations that alter levels of the neurotrophin brain-derived neurotrophic factor (BDNF) in vivo have significant effects on dendritic spine morphology, maintenance and activity-dependent plasticity for a variety of CNS neurons, yet little is known regarding BDNF effects on bulb GC spine maturation or maintenance. Here we show that, in vivo, sustained bulbar over-expression of BDNF in transgenic mice produces a marked increase in GC spine density that includes an increase in mature spines on their apical dendrites. Morphometric analysis demonstrated that changes in spine density were most notable in the distal and proximal apical domains, indicating that multiple excitatory inputs are potentially modified by BDNF. Our results indicate that increased levels of endogenous BDNF can promote the maturation and/or maintenance of dendritic spines on GCs, suggesting a role for this factor in modulating GC functional connectivity within adult olfactory circuitry. PMID:26211445

  16. Potential antidepressant properties of cysteamine on hippocampal BDNF levels and behavioral despair in mice.

    Science.gov (United States)

    Shieh, Chu-Hsin; Hong, Chen-Jee; Huang, Yn-Ho; Tsai, Shih-Jen

    2008-08-01

    Several studies have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels, suggesting that BDNF signaling is important for the therapeutic mechanism of antidepressants. Recent work has found that cysteamine and its related agent, cystamine, are neuroprotective in Huntington's disease mice, and act by enhancing the secretion of central BDNF. In the present study, the potential antidepressant effects of cysteamine were examined by behavioral paradigms and biochemical assay. Male BALB/CByJ mice were given a single dose of normal saline, 10 mg/kg of imipramine or either 50, 100 or 200 mg/kg of cysteamine (i.p.) 30 min before undergoing the forced-swimming test (FST) or the tail suspension test (TST). Other groups of mice treated with the same drugs and doses, without behavioral tests, were sacrificed for hippocampal BDNF measurements. We found that, compared with the control group, the cysteamine 200-mg/kg group showed a significant reduction in immobility time in the FST (Pcysteamine 200-mg/kg group (Pcysteamine may possess an antidepressant-like effect, which may be mediated by increasing central BDNF levels. PMID:18582526

  17. Cysteamine-related agents could be potential antidepressants through increasing central BDNF levels.

    Science.gov (United States)

    Tsai, Shih-Jen

    2006-01-01

    Major depressive disorder (MDD) is a common mental disease, but with an unknown etiology. Antidepressants are the main biological treatment for MDD. However, current antidepressive agents have a slow onset of effect and a substantial proportion of MDD patients do not clinically improve, despite maximal medication. Thus, the exploration for new antidepressants with novel strategies may help to develop faster and more effective antidepressant agents. Studies in the recent decades have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels and activating the BDNF-signaling pathway may play an important role in their therapeutic mechanism. Cysteamine is a natural product of cells and constitutes the terminal region of the CoA molecule. Recent work has found that cysteamine and a related agent, cystamine, have neuroprotective effects in Huntington's disease (HD) mice, through enhancing central BDNF levels. Furthermore, cystamine or cysteamine injection could increase serum BDNF levels in wild-type mice as well as HD mice. Since activation of the BDNF-dependent pathway plays an important role in the mechanism of antidepressant therapeutic action, cystamine or its derivatives could have potential antidepressant therapeutic effects. Among these agents, pantethine may be one of the most promising agents. It is a naturally occurring compound which can be administered orally with negligible side effects, and is metabolized to cysteamine. Further evaluation of the therapeutic and toxic effects of these cysteamine-related antidepressant agents in MDD animal models is needed before any clinical application. PMID:16797865

  18. Essential role of presynaptic NMDA receptors in activity-dependent BDNF secretion and corticostriatal LTP.

    Science.gov (United States)

    Park, Hyungju; Popescu, Andrei; Poo, Mu-ming

    2014-12-01

    Activation of N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) in postsynaptic dendrites is required for long-term potentiation (LTP) of many excitatory synapses, but the role of presynaptic axonal NMDARs in synaptic plasticity remains to be clarified. Here we report that axonal NMDARs play an essential role in LTP induction at mouse corticostriatal synapses by triggering activity-induced presynaptic secretion of brain-derived neurotrophic factor (BDNF). Genetic depletion of either BDNF or the NMDAR subunit GluN1 specifically in cortical axons abolished corticostriatal LTP in response to theta burst stimulation (TBS). Furthermore, functional axonal NMDARs were required for TBS-triggered prolonged axonal Ca(2+) elevation and BDNF secretion, supporting the notion that activation of axonal NMDARs induces BDNF secretion via enhancing Ca(2+) signals in the presynaptic nerve terminals. These results demonstrate that presynaptic NMDARs are equally important as postsynaptic NMDARs in LTP induction of corticostriatal synapses due to their role in mediating activity-induced presynaptic BDNF secretion. PMID:25467984

  19. Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats.

    Science.gov (United States)

    Niknazar, Somayeh; Nahavandi, Arezo; Peyvandi, Ali Asghar; Peyvandi, Hassan; Akhtari, Amin Shams; Karimi, Mohsen

    2016-08-01

    Studies show that gender plays an important role in stress-related disorders, and women are more vulnerable to its effect. The present study was undertaken to investigate differences in the change in expression of brain-derived neurotrophic factor (BDNF), and its tyrosine intracellular kinase-activating receptor (TrkB) genes in the male and female rats' hippocampus (HPC) under chronic mild repeated stress (CMRS) conditions. In this experiment, male and female Wistar rats were randomly divided into two groups: the CMRS and the control group. To induce stress, a repeated forced swimming paradigm was employed daily for adult male and female rats for 21 days. At the end of the stress phase, elevated plus maze (EPM) was used for measuring the stress behavioral effects. Serum corticosterone level was measured by ELISA. BDNF and TrkB gene methylation and protein expression in the HPC were detected using real-time PCR and Western blotting. Chronic stress in the adolescence had more effects on anxiety-like behavior and serum corticosterone concentration in female rats than males. Furthermore, stressed female rats had higher methylation levels and following reduced protein expression of BDNF but not TrkB compared to stressed male rats. These findings suggest that in exposure to a stressor, sex differences in BDNF methylation may be root cause of decreased BDNF levels in females and may underlie susceptibility to pathology development. PMID:26189832

  20. Amitriptyline induces brain-derived neurotrophic factor (BDNF) mRNA expression through ERK-dependent modulation of multiple BDNF mRNA variants in primary cultured rat cortical astrocytes and microglia.

    Science.gov (United States)

    Hisaoka-Nakashima, Kazue; Kajitani, Naoto; Kaneko, Masahiro; Shigetou, Takahiro; Kasai, Miho; Matsumoto, Chie; Yokoe, Toshiki; Azuma, Honami; Takebayashi, Minoru; Morioka, Norimitsu; Nakata, Yoshihiro

    2016-03-01

    A significant role of brain-derived neurotrophic factor (BDNF) has been previously implicated in the therapeutic effect of antidepressants. To ascertain the contribution of specific cell types in the brain that produce BDNF following antidepressant treatment, the effects of the tricyclic antidepressant amitriptyline on rat primary neuronal, astrocytic and microglial cortical cultures were examined. Amitriptyline increased the expression of BDNF mRNA in astrocytic and microglial cultures but not neuronal cultures. Antidepressants with distinct mechanisms of action, such as clomipramine, duloxetine and fluvoxamine, also increased BDNF mRNA expression in astrocytic and microglial cultures. There are multiple BDNF mRNA variants (exon I, IIA, IV and VI) expressed in astrocytes and microglia and the variant induced by antidepressants has yet to be elaborated. Treatment with antidepressants increased the expression of exon I, IV and VI in astrocyte and microglia. Clomipramine alone significantly upregulated expression of exon IIA. The amitriptyline-induced expression of both total and individual BDNF mRNA variants (exon I, IV and VI) were blocked by MEK inhibitor U0126, indicating MEK/ERK signaling is required in the expression of BDNF. These findings indicate that non-neural cells are a significant target of antidepressants and further support the contention that glial production of BDNF is crucial role in the therapeutic effect of antidepressants. The current data suggest that targeting of glial function could lead to the development of antidepressants with a truly novel mechanism of action. PMID:26764533

  1. 31P NMR study of improvement in oxidative phosphorylation by vitamins K3 and C in a patient with a defect in electron transport at complex III in skeletal muscle.

    OpenAIRE

    Eleff, S; Kennaway, N G; Buist, N R; Darley-Usmar, V M; Capaldi, R A; Bank, W J; Chance, B

    1984-01-01

    The bioenergetic capacity of skeletal muscle in a 17-year-old patient with a severe defect in complex III of the electron transport chain has been examined by 31P NMR measurements of the molar ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Resting ratios were 1.3-2.5, which can be compared with roughly 8.6 for a young, normal female control at rest. Quantitative evaluation of the activity of oxidative metabolism was afforded by the rate of recovery of PCr/Pi from exercise and was f...

  2. Viral depletion of VTA BDNF in rats modulates social behavior, consequences of intermittent social defeat stress, and long-term weight regulation

    OpenAIRE

    Fanous, Sanya; Terwilliger, Ernest F; Hammer, Ronald P.; Nikulina, Ella M.

    2011-01-01

    Mesolimbic brain-derived neurotrophic factor (BDNF) is implicated in sustained behavioral changes following chronic social stress, and its depletion may reduce susceptibility to such behavioral alterations. Enhanced mesolimbic BDNF is proposed as pro-depressive and anhedonic, while depleting ventral tegmetal area (VTA) BDNF increases weight by enhancing hedonic eating. Here, we questioned whether depletion of VTA BDNF would alleviate social defeat stress-induced deficits in weight regulation,...

  3. Plasma BDNF Is Reduced among Middle-Aged and Elderly Women with Impaired Insulin Function: Evidence of a Compensatory Mechanism

    Science.gov (United States)

    Arentoft, Alyssa; Sweat, Victoria; Starr, Vanessa; Oliver, Stephen; Hassenstab, Jason; Bruehl, Hannah; Tirsi, Aziz; Javier, Elizabeth; McHugh, Pauline F.; Convit, Antonio

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to…

  4. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate

    Science.gov (United States)

    Sleiman, Sama F; Henry, Jeffrey; Al-Haddad, Rami; El Hayek, Lauretta; Abou Haidar, Edwina; Stringer, Thomas; Ulja, Devyani; Karuppagounder, Saravanan S; Holson, Edward B; Ratan, Rajiv R; Ninan, Ipe; Chao, Moses V

    2016-01-01

    Exercise induces beneficial responses in the brain, which is accompanied by an increase in BDNF, a trophic factor associated with cognitive improvement and the alleviation of depression and anxiety. However, the exact mechanisms whereby physical exercise produces an induction in brain Bdnf gene expression are not well understood. While pharmacological doses of HDAC inhibitors exert positive effects on Bdnf gene transcription, the inhibitors represent small molecules that do not occur in vivo. Here, we report that an endogenous molecule released after exercise is capable of inducing key promoters of the Mus musculus Bdnf gene. The metabolite β-hydroxybutyrate, which increases after prolonged exercise, induces the activities of Bdnf promoters, particularly promoter I, which is activity-dependent. We have discovered that the action of β-hydroxybutyrate is specifically upon HDAC2 and HDAC3, which act upon selective Bdnf promoters. Moreover, the effects upon hippocampal Bdnf expression were observed after direct ventricular application of β-hydroxybutyrate. Electrophysiological measurements indicate that β-hydroxybutyrate causes an increase in neurotransmitter release, which is dependent upon the TrkB receptor. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF. DOI: http://dx.doi.org/10.7554/eLife.15092.001 PMID:27253067

  5. Low serum BDNF levels in depressed patients cannot be attributed to individual depressive symptoms or symptom cluster

    NARCIS (Netherlands)

    Bus, B. A. A.; Molendijk, M. L.; Penninx, B. W. J. H.; Buitelaar, J. K.; Prickaerts, J.; Elzinga, B. M.; Oude Voshaar, R. C.

    2014-01-01

    OBJECTIVES: Low serum BDNF levels have been found in depressed patients. No study has systematically investigated whether individual symptoms or symptom profiles within a depressed population contribute to low BDNF levels found in depressed subjects. METHODS: All 1070 patients with a past 6-month di

  6. Low serum BDNF levels in depressed patients cannot be attributed to individual depressive symptoms or symptom cluster

    NARCIS (Netherlands)

    Bus, B.A.; Molendijk, M.L.; Penninx, B.W.; Buitelaar, J.; Prickaerts, J.; Elzinga, B.M.; Oude Voshaar, R.C.

    2014-01-01

    Abstract Objectives. Low serum BDNF levels have been found in depressed patients. No study has systematically investigated whether individual symptoms or symptom profiles within a depressed population contribute to low BDNF levels found in depressed subjects. Methods. All 1070 patients with a past 6

  7. Brain Derived Neurotrophic Factor (BDNF) levels as a possible predictor of psychopathology in healthy twins at high and low risk for affective disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Kessing, Lars Vedel

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a potential biomarker of affective disorder. However, longitudinal studies evaluating a potential predictive role of BDNF on subsequent psychopathology are lacking. The aim of this study was to investigate whether BDNF alone or in interaction with the...

  8. Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF inducing their proliferation in an adenosine A2A receptor-dependent manner: A2A receptor blockade prevents BDNF release and proliferation of microglia

    Directory of Open Access Journals (Sweden)

    Gomes Catarina

    2013-01-01

    Full Text Available Abstract Background Brain-derived neurotrophic factor (BDNF has been shown to control microglial responses in neuropathic pain. Since adenosine A2A receptors (A2ARs control neuroinflammation, as well as the production and function of BDNF, we tested to see if A2AR controls the microglia-dependent secretion of BDNF and the proliferation of microglial cells, a crucial event in neuroinflammation. Methods Murine N9 microglial cells were challenged with lipopolysaccharide (LPS, 100 ng/mL in the absence or in the presence of the A2AR antagonist, SCH58261 (50 nM, as well as other modulators of A2AR signaling. The BDNF cellular content and secretion were quantified by Western blotting and ELISA, A2AR density was probed by Western blotting and immunocytochemistry and cell proliferation was assessed by BrdU incorporation. Additionally, the A2AR modulation of LPS-driven cell proliferation was also tested in primary cultures of mouse microglia. Results LPS induced time-dependent changes of the intra- and extracellular levels of BDNF and increased microglial proliferation. The maximal LPS-induced BDNF release was time-coincident with an LPS-induced increase of the A2AR density. Notably, removing endogenous extracellular adenosine or blocking A2AR prevented the LPS-mediated increase of both BDNF secretion and proliferation, as well as exogenous BDNF-induced proliferation. Conclusions We conclude that A2AR activation plays a mandatory role controlling the release of BDNF from activated microglia, as well as the autocrine/paracrine proliferative role of BDNF.

  9. Changes in spatial memory and BDNF expression to simultaneous dietary restriction and forced exercise.

    Science.gov (United States)

    Khabour, Omar F; Alzoubi, Karem H; Alomari, Mahmoud A; Alzubi, Mohammad A

    2013-01-01

    Previous literature suggests that learning and memory formation can be influenced by diet and exercise. In the current study, we investigated the combined effects of forced swimming exercise (FSE) and every other day fasting (EODF) on spatial memory formation and on the levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of Wistar male rats. The radial arm water maze (RAWM) paradigm was used to assess changes in learning and memory formation, whereas ELISA assay was used to measure BDNF protein levels. The FSE and/or EODF were simultaneously instituted for 6 weeks. Results show that FSE improved learning, short-term as well as long-term memory formation, and significantly increased BDNF protein in the hippocampus (p0.05). In addition, EODF did not modulate beneficial effect of swimming exercise on cognitive function (p>0.05). Thus exercise enhanced, while EODF did not affect spatial learning and memory formation. PMID:23000024

  10. Effect of Brain-derived Neurotrophic Factor (BDNF in Organotypic Retinal Cultures

    Directory of Open Access Journals (Sweden)

    N.A. Gavrilova

    2009-02-01

    Full Text Available ABSTRACT Purpose To study the influence of recombinant brain-derived neurotrophic factor (BDNF on organotypic retinal cultures. Material and methods Experiments were performed in human and rat retinal explants cultured in culture dishes, flasks and flasks for roller cultivation. BDNF was added at the concentration of 100 ng⁄ml. Cultures were tested for viability and stained immunohistochemically for neuronal markers. Culture conditions and results of cultivation were controlled using phase contrast and fluorescent microscopes. Conclusions Results of the study showed that cultivation of organotypic cultures of the human and rat retina in the presence of BDNF at the concentration of 100 ng⁄ml increases viability of retinal cells. Active cell migration and outgrowth of β-III-tubulin-positive axon-like processes of neuronal origin outside the borders of explants were observed.

  11. Late protein synthesis-dependent phases in CTA long-term memory: BDNF requirement

    Directory of Open Access Journals (Sweden)

    Martha L Escobar

    2011-09-01

    Full Text Available It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memory when protein synthesis was inhibited. Our previous studies on the insular cortex (IC, a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA, have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis dependent in different time-windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 hours after acquisition. Then, we explore the effect of BDNF delivery (2 μg/2 μl per side in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.

  12. Charged Semiconductor Defects Structure, Thermodynamics and Diffusion

    CERN Document Server

    Seebauer, Edmund G

    2009-01-01

    The technologically useful properties of a solid often depend upon the types and concentrations of the defects it contains. Not surprisingly, defects in semiconductors have been studied for many years, in many cases with a view towards controlling their behavior through various forms of "defect engineering." For example, in the bulk, charging significantly affects the total concentration of defects that are available to mediate phenomena such as solid-state diffusion. Surface defects play an important role in mediating surface mass transport during high temperature processing steps such as epitaxial film deposition, diffusional smoothing in reflow, and nanostructure formation in memory device fabrication. Charged Semiconductor Defects details the current state of knowledge regarding the properties of the ionized defects that can affect the behavior of advanced transistors, photo-active devices, catalysts, and sensors. Features: Group IV, III-V, and oxide semiconductors; Intrinsic and extrinsic defects; and, P...

  13. The liquid phase epitaxy approach for the successful construction of ultra-thin and defect-free ZIF-8 membranes: Pure and mixed gas transport study

    KAUST Repository

    Shekhah, Osama

    2014-01-01

    The liquid-phase epitaxy (LPE) method was effectively implemented to deliberately grow/construct ultrathin (0.5-1 μm) continuous and defect-free ZIF-8 membranes. Permeation properties of different gas pair systems (O 2-N2, H2-CO2, CO2-CH 4, C3H6-C3H8, CH 4-n-C4H10) were studied using the time lag technique. This journal is © The Royal Society of Chemistry.

  14. Brain-derived neurotrophic factor (BDNF as a potential mechanism of the effects of acute exercise on cognitive performance

    Directory of Open Access Journals (Sweden)

    Aaron T. Piepmeier

    2015-03-01

    Full Text Available The literature shows that improvements in cognitive performance may be observed following an acute bout of exercise. However, evidence in support of the biological mechanisms of this effect is still limited. Findings from both rodent and human studies suggest brain-derived neurotrophic factor (BDNF as a potential mechanism of the effect of acute exercise on memory. The molecular properties of BDNF allow this protein to be assessed in the periphery (pBDNF (i.e., blood serum, blood plasma, making measurements of acute exercise-induced changes in BDNF concentration relatively accessible. Studies exploring the acute exercise–pBDNF–cognitive performance relationship have had mixed findings, but this may be more reflective of methodological differences between studies than it is a statement about the role of BDNF. For example, significant associations have been observed between acute exercise-induced changes in pBDNF concentration and cognitive performance in studies assessing memory, and non-significant associations have been found in studies assessing non-memory cognitive domains. Three suggestions are made for future research aimed at understanding the role of BDNF as a biological mechanism of this relationship: 1 Assessments of cognitive performance may benefit from a focus on various types of memory (e.g., relational, spatial, long-term; 2 More fine-grained measurements of pBDNF will allow for the assessment of concentrations of specific isoforms of the BDNF protein (i.e., immature, mature; 3 Statistical techniques designed to test the mediating role of pBDNF in the acute exercise-cognitive performance relationship should be utilized in order to make causal inferences.

  15. BDNF and Exercise Enhance Neuronal DNA Repair by Stimulating CREB-Mediated Production of Apurinic/Apyrimidinic Endonuclease 1

    Science.gov (United States)

    Yang, Jenq-Lin; Lin, Yu-Ting; Chuang, Pei-Chin

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) promotes the survival and growth of neurons during brain development and mediates activity-dependent synaptic plasticity and associated learning and memory in the adult. BDNF levels are reduced in brain regions affected in Alzheimer’s, Parkinson’s, and Huntington’s diseases, and elevation of BDNF levels can ameliorate neuronal dysfunction and degeneration in experimental models of these diseases. Because neurons accumulate oxidative lesions in their DNA during normal activity and in neurodegenerative disorders, we determined whether and how BDNF affects the ability of neurons to cope with oxidative DNA damage. We found that BDNF protects cerebral cortical neurons against oxidative DNA damage-induced death by a mechanism involving enhanced DNA repair. BDNF stimulates DNA repair by activating cyclic AMP response element-binding protein (CREB), which, in turn, induces the expression of apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme in the base excision DNA repair pathway. Suppression of either APE1 or TrkB by RNA interference abolishes the ability of BDNF to protect neurons against oxidized DNA damage-induced death. The ability of BDNF to activate CREB and upregulate APE1 expression is abolished by shRNA of TrkB as well as inhibitors of TrkB, PI3 kinase, and Akt kinase. Voluntary running wheel exercise significantly increases levels of BDNF, activates CREB, and upregulates APE1 in the cerebral cortex and hippocampus of mice, suggesting a novel mechanism whereby exercise may protect neurons from oxidative DNA damage. Our findings reveal a previously unknown ability of BDNF to enhance DNA repair by inducing the expression of the DNA repair enzyme APE1. PMID:24114393

  16. Molecular mechanisms underlying the regulation of brain-derived neurotrophic factor (BDNF) translation in dendrites

    OpenAIRE

    Pinheiro, Vera Lúcia Margarido

    2010-01-01

    A especificidade espacial e temporal subjacente à diversidade de processos de plasticidade sináptica que ocorrem no sistema nervoso central está profundamente relacionada com a disponibilidade da proteína brain-derived neurotrophic factor (BDNF) em domínios sub-celulares distintos, especialmente na área pós-sináptica. Contudo, os mecanismos moleculares que regulam a síntese proteica de BDNF nas dendrites estão ainda por desvendar. Assim, o principal objectivo deste trabalho foi...

  17. Juvenile methylphenidate reduces prefrontal cortex plasticity via D3 receptor and BDNF in adulthood

    Directory of Open Access Journals (Sweden)

    Susan L Andersen

    2014-01-01

    Full Text Available Background: Early drug intervention in childhood disorders aims to maximize individual potential in the short- and long-term. Consistently, juvenile exposure to psychostimulants, such as methylphenidate (MPH, reduces risk for substance use in animals and sub-populations of individuals with attention deficit hyperactivity disorder (ADHD. We investigated the effects of MPH on brain plasticity via dopamine receptor D3 (D3R and brain-derived neurotrophic factor (BDNF expression in developing rats. Methods: Between postnatal days 20-35, rat pups were administered saline vehicle (Veh or MPH (2 mg/kg, the D3R-preferring agonist ± 7-OHDPAT, or the antagonist nafadotride (0.05 mg/kg alone, or in combination with MPH twice a day. In adulthood, subjects were challenged to Veh or cocaine (10 mg/kg for two days. The prefrontal cortex was analyzed for protein and mRNA levels of total BDNF, its splice variants I, IIc, III/IV, and IV/VI, and D3 receptors. A separate group of subjects was assessed for splice variants at 20, 35, 40 and 60 days. Results: Across age strong correlations were evident between Drd3 and Bdnf mRNA levels (r=0.65 and a negative relationship between Drd3 and exon IIc after MPH exposure (r=-0.73. BDNF protein levels did not differ between Veh- and MPH subjects at baseline, but were significantly lower in MPH-treated and cocaine challenged subjects (30.3 ± 9.7%. Bdnf mRNA was significantly higher in MPH subjects, and reversed upon exposure to cocaine. This effect was blocked by nafadotride. Furthermore, Bdnftotal and Bdnf splice variants I, IIc, III/IV, and IV/VI changed across the transitions between juvenility and late adolescence. Conclusions: These data suggest a sensitive window of vulnerability to modulations of BDNF expression around adolescence, and that compared to normal animals, juvenile exposure to MPH permanently reduces prefrontal BDNF transcription and translation upon cocaine exposure in adulthood by a D3R

  18. Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

    OpenAIRE

    Escobar, Martha L.

    2011-01-01

    It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memo...

  19. Expression and Role of the BDNF Receptor-TrkB in Rat Adrenal Gland under Acute Immobilization Stress

    International Nuclear Information System (INIS)

    We reported that plasma brain-derived neurotrophic factor (BDNF) was maximally elevated following a 60-min period of acute immobilization stress and that salivary glands were the main source of plasma BDNF under this stress condition. However, the expression pattern of the BDNF receptor, Tyrosine receptor kinase B (TrkB), under this condition has yet to be determined. We therefore investigated the effect of this stress on the expression level of TrkB in various rat organs using real-time PCR. No significant differences were found between controls and 60 min-stressed rats with respect to TrkB level in various organs. Only adrenal glands showed significantly increased TrkB mRNA levels after 60 min of stress. TrkB mRNA and protein were observed to localize in chromaffin cells. In addition, we investigated whether BDNF-TrkB interaction influences the release of stress hormones from PC12 cells, derived from chromaffin cells. Truncated receptor, TrkB-T1, was identified in PC12 cells using RT-PCR. Exposure of PC12 cells to BDNF induced the release of catecholamine. This BDNF-evoked release was totally blocked by administration of the K252a in which an inhibitor of Trk receptors. Thus, BDNF-TrkB interactions may modulate catecholamine release from adrenal chromaffin cells under acute stress conditions

  20. Nitric oxide regulates BDNF release from nodose ganglion neurons in a pattern-dependent and cGMP-independent manner.

    Science.gov (United States)

    Hsieh, Hui-ya; Robertson, Carolyn L; Vermehren-Schmaedick, Anke; Balkowiec, Agnieszka

    2010-05-01

    Activity of arterial baroreceptors is modulated by neurohumoral factors, including nitric oxide (NO), released from endothelial cells. Baroreceptor reflex responses can also be modulated by NO signaling in the brainstem nucleus tractus solitarius (NTS), the primary central target of cardiovascular afferents. Our recent studies indicate that brain-derived neurotrophic factor (BDNF) is abundantly expressed by developing and adult baroreceptor afferents in vivo, and released from cultured nodose ganglion (NG) neurons by patterns of baroreceptor activity. Using electrical field stimulation and ELISA in situ, we show that exogenous NO nearly abolishes BDNF release from newborn rat NG neurons in vitro stimulated with single pulses delivered at 6 Hz, but not 2-pulse bursts delivered at the same 6-Hz frequency, that corresponds to a rat heart rate. Application of L-NAME, a specific inhibitor of endogenous NO synthases, does not have any significant effect on activity-dependent BDNF release, but leads to upregulation of BDNF expression in an activity-dependent manner. The latter effect suggests a novel mechanism of homeostatic regulation of activity-dependent BDNF expression with endogenous NO as a key player. The exogenous NO-mediated effect does not involve the cGMP-protein kinase G (PKG) pathway, but is largely inhibited by N-ethylmaleimide and TEMPOL that are known to prevent S-nitrosylation. Together, our current data identify previously unknown mechanisms regulating BDNF availability, and point to NO as a likely regulator of BDNF at baroafferent synapses in the NTS. PMID:19937808

  1. Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

    Directory of Open Access Journals (Sweden)

    Wenda Xue

    2013-01-01

    Full Text Available The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2, leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression.

  2. Depression, the Val66Met polymorphism, age, and gender influence the serum BDNF level

    DEFF Research Database (Denmark)

    Elfving, Betina; Buttenschøn, Henriette N; Foldager, Leslie;

    2012-01-01

    participated in a semi-structured diagnostic interview. The major contribution of the present study is the integration of clinical assessment of cases and control individuals, simultaneous analyses of several genetic variants, serum BDNF measurements, and information on socio-demographic variables, lifestyle...

  3. Action control is mediated by prefrontal BDNF and glucocorticoid receptor binding.

    Science.gov (United States)

    Gourley, Shannon L; Swanson, Andrew M; Jacobs, Andrea M; Howell, Jessica L; Mo, Michelle; Dileone, Ralph J; Koleske, Anthony J; Taylor, Jane R

    2012-12-11

    Stressor exposure biases decision-making strategies from those based on the relationship between actions and their consequences to others restricted by stimulus-response associations. Chronic stressor exposure also desensitizes glucocorticoid receptors (GR) and diminishes motivation to acquire food reinforcement, although causal relationships are largely not established. We show that a history of chronic exposure to the GR ligand corticosterone or acute posttraining GR blockade with RU38486 makes rodents less able to perform actions based on their consequences. Thus, optimal GR binding is necessary for the consolidation of new response-outcome learning. In contrast, medial prefrontal (but not striatal) BDNF can account for stress-related amotivation, in that selective medial prefrontal cortical Bdnf knockdown decreases break-point ratios in a progressive-ratio task. Knockdown also increases vulnerability to RU38486. Despite the role of BDNF in dendritic spine reorganization, deep-layer spine remodeling does not obviously parallel progressive-ratio response patterns, but treatment with the Na(+)-channel inhibitor riluzole reverses corticosteroid-induced motivational deficits and restores prefrontal BDNF expression after corticosterone. We argue that when prefrontal neurotrophin systems are compromised, and GR-mediated hypothalamic-pituitary-adrenal axis feedback is desensitized (as in the case of chronic stress hormone exposure), amotivation and inflexible maladaptive response strategies that contribute to stress-related mood disorders result. PMID:23185000

  4. Antihypoxic and Neuroprotective Properties of BDNF and GDNF in vitro and in vivo Under Hypoxic Conditions

    Directory of Open Access Journals (Sweden)

    Vedunova М.V.

    2014-12-01

    Full Text Available The aim of the investigation was to assess antihypoxic and neuroprotective properties of the brain-derived neurotrophic factor (BDNF and the glial cell line-derived neurotrophic factor (GDNF during in vitro and in vivo hypoxia models. Materials and Methods. In vitro studies were performed using hippocampal cells dissociated from 18-days embryonic CBA mice and cultured on multielectrode arrays (MEA60. Hypoxia modeling was performed on day 14 of culture development in vitro by replacing the normoxic culture medium with a medium containing low oxygen for 10 min. In vivo experiments were carried out on C57BL/6j male mice weighing 18–20 g. For acute hypobaric hypoxia a vacuum flow-through chamber was used at the ambient temperature of 20–22°C. We studied the resistance of animals to hypoxia, as well as their spatial memory retention in the Morris water maze upon expiration of 24 h following hypoxia model. Results. The carried out in vitro and in vivo experiments revealed that BDNF and GDNF have strong antihypoxic and neuroprotective effects. Preventive application of BDNF plus GDNF before testing in the Morris water maze, contributed less animal resistance and retention of spatial memory as well as the viability of cells in dissociated hippocampal cultures was decreased in comparison with the isolated effect each of these factors. Conclusion. Application of BDNF in combination with GDNF under hypoxic conditions reduces the positive individual effect these neurotrophic factors.

  5. High dose zinc supplementation induces hippocampal zinc deficiency and memory impairment with inhibition of BDNF signaling.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose, 60 ppm Zn (high dose or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit.

  6. Gastric Bypass Surgery Reverses Diabetic Phenotypes in Bdnf-Deficient Mice.

    Science.gov (United States)

    Jiang, Shujun; Wang, Qinghua; Huang, Zan; Song, Anying; Peng, Yu; Hou, Siyuan; Guo, Shiying; Zhu, Weiyun; Yan, Sheng; Lin, Zhaoyu; Gao, Xiang

    2016-08-01

    Duodenum-jejunum gastric bypass (DJB) has been used to treat morbid diabetic patients. However, neither the suitability among patients nor the mechanisms of this surgical treatment is clear. Previously, we reported a new mouse strain named Timo as type 2 diabetes model caused by brain-derived neurotrophic factor (Bdnf) deficiency. In this study, we found that DJB on Timo mice reversed their metabolic abnormalities without altering the expression of Bdnf. Glucose tolerance and insulin sensitivity were improved greatly, along with reduction of fat accumulation in liver and white adipose tissue. The gut flora population was altered by DJB with increased proportion of Firmicutes and decreased Actinobacteria and Proteobacteria in the ileum after surgery. Systemic inflammation in Timo mice was greatly suppressed with less macrophage infiltration and lower tumor necrosis factor-α levels in liver and white adipose tissue after surgery. Interestingly, the alteration of gut microflora abundance and improved metabolism preceded the inflammation alleviation after DJB surgery. These results suggested that DJB can reverse Bdnf deficiency-associated metabolic abnormality. In addition, the reduced inflammation may not be the initial cause for the DJB-associated metabolic and microbiota alterations. The increased BDNF protein levels in hypothalamus and hippocampus may result from microbiota change after DJB surgery. PMID:27418549

  7. BDNF selectively regulates GABAA receptor transcription by activation of the JAK/STAT pathway.

    Science.gov (United States)

    Lund, Ingrid V; Hu, Yinghui; Raol, YogendraSinh H; Benham, Rebecca S; Faris, Ramona; Russek, Shelley J; Brooks-Kayal, Amy R

    2008-01-01

    The gamma-aminobutyric acid (GABA) type A receptor (GABA(A)R) is the major inhibitory neurotransmitter receptor in the brain. Its multiple subunits show regional, developmental, and disease-related plasticity of expression; however, the regulatory networks controlling GABA(A)R subunit expression remain poorly understood. We report that the seizure-induced decrease in GABA(A)R alpha1 subunit expression associated with epilepsy is mediated by the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway regulated by brain-derived neurotrophic factor (BDNF). BDNF- and seizure-dependent phosphorylation of STAT3 cause the adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) family member ICER (inducible cAMP early repressor) to bind with phosphorylated CREB at the Gabra1:CRE site. JAK/STAT pathway inhibition prevents the seizure-induced decrease in GABA(A)R alpha1 abundance in vivo and, given that BDNF is known to increase the abundance of GABA(A)R alpha4 in a JAK/STAT-independent manner, indicates that BDNF acts through at least two distinct pathways to influence GABA(A)R-dependent synaptic inhibition. PMID:18922788

  8. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. PMID:26965573

  9. Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation.

    Science.gov (United States)

    Griesbach, Grace Sophia; Hovda, David Allen; Gomez-Pinilla, Fernando

    2009-09-01

    We have previously shown that voluntary exercise upregulates brain derived neurotrophic factor (BDNF) within the hippocampus and is associated with an enhancement of cognitive recovery after a lateral fluid percussion injury (FPI). In order to determine if BDNF is critical to this effect we used an immunoadhesin chimera (TrkB-IgG) that inactivates free BDNF. This BDNF inhibitor was administered to adult male rats two weeks after they had received a mild fluid percussion injury (FPI) or sham surgery. These animals were then housed with or without access to a running wheel (RW) from post-injury-day (PID) 14 to 20. On PID 21, rats were tested for spatial learning in a Morris Water Maze. Results showed that exercise counteracted the cognitive deficits associated with the injury. However this exercise-induced cognitive improvement was attenuated in the FPI-RW rats that were treated with TrkB-IgG. Molecules important for synaptic plasticity and learning were measured in a separate group of rats that were sacrificed immediately after exercise (PID 21). Western blot analyses showed that exercise increased the mature form of BDNF, synapsin I and cyclic-AMP response-element-binding protein (CREB) in the vehicle treated Sham-RW group. However, only the mature form of BDNF and CREB were increased in the vehicle treated FPI-RW group. Blocking BDNF (pre administration of TrkB-IgG) greatly reduced the molecular effects of exercise in that exercise-induced increases of BDNF, synapsin I and CREB were not observed. These studies provide evidence that BDNF has a major role in exercise's cognitive effects in traumatically injured brain. PMID:19555673

  10. TUMOR NECROSIS FACTOR-α INCREASES BDNF EXPRESSION IN TRIGEMINAL GANGLION NEURONS IN AN ACTIVITY-DEPENDENT MANNER

    Science.gov (United States)

    Bałkowiec-Iskra, Ewa; Vermehren-Schmaedick, Anke; Balkowiec, Agnieszka

    2011-01-01

    Many chronic trigeminal pain conditions, such as migraine or temporo-mandibular disorders, are associated with inflammation within peripheral endings of trigeminal ganglion (TG) sensory neurons. A critical role in mechanisms of neuroinflammation is attributed to proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α (TNFα) that also contribute to mechanisms of persistent neuropathic pain resulting from nerve injury. However, the mechanisms of cytokine-mediated synaptic plasticity and nociceptor sensitization are not completely understood. In the present study, we examined the effects of TNFα on neuronal expression of brain-derived neurotrophic factor (BDNF), whose role in synaptic plasticity and sensitization of nociceptive pathways is well documented. We show that 4- and 24-hr treatment with TNFα increases BDNF mRNA and protein, respectively, in neuron-enriched dissociated cultures of rat TG. TNFα increases the phosphorylated form of the cyclic adenosine monophosphate-responsive element binding protein (CREB), a transcription factor involved in regulation of BDNF expression in neurons, and activates transcription of BDNF exon IV (former exon III) and, to a lesser extent, exon VI (former exon IV), but not exon I. TNFα-mediated increase in BDNF expression was accompanied by increase in calcitonin gene-related peptide (CGRP), which is consistent with previously published studies, and indicates that both peptides are similarly regulated in TG neurons by inflammatory mediators. The effect of TNFα on BDNF expression is dependent on sodium influx through TTX-sensitive channels and on p38-mitogen-activated protein kinase. Moreover, electrical stimulation and forskolin, known to increase intracellular cAMP, potentiate the TNFα-mediated upregulation of BDNF expression. This study provides new evidence for a direct action of proinflammatory cytokines on TG primary sensory neurons, and reveals a mechanism through which TNFα stimulates de novo

  11. Effects of the BDNF Val66Met Polymorphism on Gray Matter Volume in Typically Developing Children and Adolescents

    OpenAIRE

    Hashimoto, Teruo; Fukui, Kento; Takeuchi, Hikaru; Yokota, Susumu; Kikuchi, Yoshie; Tomita, Hiroaki; Taki, Yasuyuki; Kawashima, Ryuta

    2016-01-01

    The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) is associated with psychiatric disorders and regional gray matter volume (rGMV) in adults. However, the relationship between BDNF and rGMV in children has not been clarified. In this 3-year cross-sectional/longitudinal (2 time points) study, we investigated the effects of BDNF genotypes on rGMV in 185 healthy Japanese children aged 5.7–18.4 using magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analyses. W...

  12. Early life stress increases stress vulnerability through BDNF gene epigenetic changes in the rat hippocampus.

    Science.gov (United States)

    Seo, Mi Kyoung; Ly, Nguyen Ngoc; Lee, Chan Hong; Cho, Hye Yeon; Choi, Cheol Min; Nhu, Le Hoa; Lee, Jung Goo; Lee, Bong Ju; Kim, Gyung-Mee; Yoon, Bong June; Park, Sung Woo; Kim, Young Hoon

    2016-06-01

    Early life stress (ELS) exerts long-lasting epigenetic influences on the brain and makes an individual susceptible to later depression. It is poorly understood whether ELS and subsequent adult chronic stress modulate epigenetic mechanisms. We examined the epigenetic mechanisms of the BDNF gene in the hippocampus, which may underlie stress vulnerability to postnatal maternal separation (MS) and adult restraint stress (RS). Rat pups were separated from their dams (3 h/day from P1-P21). When the pups reached adulthood (8 weeks old), we introduced RS (2 h/day for 3 weeks) followed by escitalopram treatment. We showed that both the MS and RS groups expressed reduced levels of total and exon IV BDNF mRNA. Furthermore, RS potentiated MS-induced decreases in these expression levels. Similarly, both the MS and RS groups showed decreased levels of acetylated histone H3 and H4 at BDNF promoter IV, and RS exacerbated MS-induced decreases of H3 and H4 acetylation. Both the MS and RS groups had increased MeCP2 levels at BDNF promoter IV, as well as increased HDAC5 mRNA, and the combination of MS and RS exerted a greater effect on these parameters than did RS alone. In the forced swimming test, the immobility time of the MS + RS group was significantly higher than that of the RS group. Additionally, chronic escitalopram treatment recovered these alterations. Our results suggest that postnatal MS and subsequent adult RS modulate epigenetic changes in the BDNF gene, and that these changes may be related to behavioral phenotype. These epigenetic mechanisms are involved in escitalopram action. PMID:26877199

  13. BDNF modulates GABAA receptors microtransplanted from the human epileptic brain to Xenopus oocytes

    Science.gov (United States)

    Palma, E.; Torchia, G.; Limatola, C.; Trettel, F.; Arcella, A.; Cantore, G.; Di Gennaro, G.; Manfredi, M.; Esposito, V.; Quarato, P. P.; Miledi, R.; Eusebi, F.

    2005-01-01

    Cell membranes isolated from brain tissues, obtained surgically from six patients afflicted with drug-resistant temporal lobe epilepsy and from one nonepileptic patient afflicted with a cerebral oligodendroglioma, were injected into frog oocytes. By using this approach, the oocytes acquire human GABAA receptors, and we have shown previously that the “epileptic receptors” (receptors transplanted from epileptic brains) display a marked run-down during repetitive applications of GABA. It was found that exposure to the neurotrophin BDNF increased the amplitude of the “GABA currents” (currents elicited by GABA) generated by the epileptic receptors and decreased their run-down; both events being blocked by K252A, a neurotrophin tyrosine kinase receptor B inhibitor. These effects of BDNF were not mimicked by nerve growth factor. In contrast, the GABAA receptors transplanted from the nonepileptic human hippocampal uncus (obtained during surgical resection as part of the nontumoral tissue from the oligodendroglioma margins) or receptors expressed by injecting rat recombinant α1β2γ2 GABAA receptor subunit cDNAs generated GABA currents whose time-course and run-down were not altered by BDNF. Loading the oocytes with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate-acetoxymethyl ester (BAPTA-AM), or treating them with Rp-8-Br-cAMP, an inhibitor of the cAMP-dependent PKA, did not alter the GABA currents. However, staurosporine (a broad spectrum PK inhibitor), bisindolylmaleimide I (a PKC inhibitor), and U73122 (a phospholipase C inhibitor) blocked the BDNF-induced effects on the epileptic GABA currents. Our results indicate that BDNF potentiates the epileptic GABAA currents and antagonizes their use-dependent run-down, thus strengthening GABAergic inhibition, probably by means of activation of tyrosine kinase receptor B receptors and of both PLC and PKC. PMID:15665077

  14. International conference on defects in insulating crystals

    International Nuclear Information System (INIS)

    Short summaries of conference papers are presented. Some of the conference topics included transport properties, defect levels, superionic conductors, radiation effects, John-Teller effect, electron-lattice interactions, and relaxed excited states

  15. International conference on defects in insulating crystals

    Energy Technology Data Exchange (ETDEWEB)

    1977-01-01

    Short summaries of conference papers are presented. Some of the conference topics included transport properties, defect levels, superionic conductors, radiation effects, John-Teller effect, electron-lattice interactions, and relaxed excited states. (SDF)

  16. A Bovine Herpesvirus Type 1 Mutant Virus Specifying a Carboxyl-Terminal Truncation of Glycoprotein E Is Defective in Anterograde Neuronal Transport in Rabbits and Calves▿ †

    OpenAIRE

    Liu, Z. F.; M.C.S. Brum; Doster, A.; Jones, C.; Chowdhury, S I

    2008-01-01

    Bovine herpesvirus type 1 (BHV-1) is an important component of the bovine respiratory disease complex (BRDC) in cattle. The ability of BHV-1 to transport anterogradely from neuronal cell bodies in trigeminal ganglia (TG) to nerve ending in the noses and corneas of infected cattle following reactivation from latency plays a significant role in the pathogenesis of BRDC and maintenance of BHV-1 in the cattle population. We have constructed a BHV-1 bacterial artificial chromosome (BAC) clone by i...

  17. No exercise-induced increase in serum BDNF after cycling near a major traffic road.

    Science.gov (United States)

    Bos, I; Jacobs, L; Nawrot, T S; de Geus, B; Torfs, R; Int Panis, L; Degraeuwe, B; Meeusen, R

    2011-08-15

    Commuting by bike has a clear health enhancing effect. Moreover, regular exercise is known to improve brain plasticity, which results in enhanced cognition and memory performance. Animal research has clearly shown that exercise upregulates brain-derived neurotrophic factor (BDNF - a neurotrophine) enhancing brain plasticity. Studies in humans found an increase in serum BDNF concentration in response to an acute exercise bout. Recently, more evidence is emerging suggesting that exposure to air pollution (such as particulate matter (PM)) is higher in commuter cyclists compared to car drivers. Furthermore, exposure to PM is linked to negative neurological effects, such as neuroinflammation and cognitive decline. We carried-out a cross-over experiment to examine the acute effect of exercise on serum BDNF, and the potential effect-modification by exposure to traffic-related air pollution. Thirty eight physically fit, non-asthmatic volunteers (mean age: 43, 26% women) performed two cycling trials, one near a major traffic road (Antwerp Ring, R1, up to 260,000 vehicles per day) and one in an air-filtered room. The air-filtered room was created by reducing fine particles as well as ultrafine particles (UFP). PM10, PM2.5 and UFP were measured. The duration (∼20min) and intensity of cycling were kept the same for each volunteer for both cycling trials. Serum BDNF concentrations were measured before and 30min after each cycling trial. Average concentrations of PM10 and PM2.5 were 64.9μg/m(3) and 24.6μg/m(3) in cycling near a major ring way, in contrast to 7.7μg/m(3) and 2.0μg/m(3) in the air-filtered room. Average concentrations of UFP were 28,180 particles/cm(3) along the road in contrast to 496 particles/cm(3) in the air-filtered room. As expected, exercise significantly increased serum BDNF concentration after cycling in the air-filtered room (+14.4%; p=0.02). In contrast, serum BDNF concentrations did not increase after cycling near the major traffic route (+0.5%; p

  18. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus

    OpenAIRE

    Vahdati Hassani, Faezeh; Naseri, Vahideh; Razavi, BiBi Marjan; Mehri, Soghra; Abnous, Khalil; Hosseinzadeh, Hossein

    2014-01-01

    Background Antidepressants have been shown to affect levels of brain-derived neurotrophic factor (BDNF) and VGF (non-acronymic) whose transcriptions are dependent on cAMP response element binding protein (CREB) in long term treatment. The aim of this study was to verify the subacute antidepressant effects of crocin, an active constituent of saffron (Crocus sativus L.), and its effects on CREB, BDNF, and VGF proteins, transcript levels and amount of active, phosphorylated CREB (P-CREB) protein...

  19. Association of decreased serum brain-derived neurotrophic factor (BDNF) concentrations in early pregnancy with antepartum depression

    OpenAIRE

    Fung, Jenny; Gelaye, Bizu; Zhong, Qiu-Yue; Rondon, Marta B; Sanchez, Sixto E; Barrios, Yasmin V; Hevner, Karin; Qiu, Chunfang; Williams, Michelle A.

    2015-01-01

    Background Antepartum depression is one of the leading causes of maternal morbidity and mortality in the prenatal period. There is accumulating evidence for the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression. The present study examines the extent to which maternal early pregnancy serum BDNF levels are associated with antepartum depression. Method A total of 968 women were recruited and interviewed in early pregnancy. Antepartum depression prevalence and ...

  20. Association of decreased serum brain-derived neurotrophic factor (BDNF) concentrations in early pregnancy with antepartum depression

    OpenAIRE

    Fung, Jenny; Gelaye, Bizu; Zhong, Qiu-Yue; Rondon, Marta B; Sanchez, Sixto E; Barrios, Yasmin V; Hevner, Karin; Qiu, Chunfang; Williams, Michelle A.

    2015-01-01

    Background: Antepartum depression is one of the leading causes of maternal morbidity and mortality in the prenatal period. There is accumulating evidence for the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression. The present study examines the extent to which maternal early pregnancy serum BDNF levels are associated with antepartum depression. Method A total of 968 women were recruited and interviewed in early pregnancy. Antepartum depression prevalence and...

  1. Chronic Unpredictable Stress Decreases Expression of Brain-Derived Neurotrophic Factor (BDNF) in Mouse Ovaries: Relationship to Oocytes Developmental Potential

    OpenAIRE

    Li-Min Wu; Mei-Hong Hu; Xian-Hong Tong; Hui Han; Ni Shen; Ren-Tao Jin; Wei Wang; Gui-Xiang Zhou; Guo-Ping He; Yu-Sheng Liu

    2012-01-01

    BACKGROUND: Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chroni...

  2. Effects of BDNF polymorphism and physical activity on episodic memory in the elderly: a cross sectional study

    OpenAIRE

    Canivet, Anne; Albinet, Cédric T.; André, Nathalie; Pylouster, Jean; Rodríguez-Ballesteros, Montserrat; Kitzis, Alain; Audiffren, Michel

    2015-01-01

    Background The brain-derived neurotrophic factor (BDNF) concentration is highest in the hippocampus compared with that in other brain structures and affects episodic memory, a cognitive function that is impaired in older adults. According to the neurotrophic hypothesis, BDNF released during physical activity enhances brain plasticity and consequently brain health. However, even if the physical activity level is involved in the secretion of neurotrophin, this protein is also under the control ...

  3. BDNF Val66Met and 5-HTTLPR Genotype are Each Associated with Visual Scanning Patterns of Faces in Young Children

    OpenAIRE

    Christou, Antonios I.; Wallis, Yvonne; Bair, Hayley; Crawford, Hayley; Frisson, Steven; Zeegers, Maurice P; McCleery, Joseph P.

    2015-01-01

    Previous studies have documented both neuroplasticity-related BDNF Val66Met and emotion regulation-related 5-HTTLPR polymorphisms as genetic variants that contribute to the processing of emotions from faces. More specifically, research has shown the BDNF Met allele and the 5-HTTLPR Short allele to be associated with mechanisms of negative affectivity that relate to susceptibility for psychopathology. We examined visual scanning pathways in response to angry, happy, and neutral faces in relati...

  4. BDNF Val66Met genotype modulates the effect of childhood adversity on subgenual anterior cingulate cortex volume in healthy subjects

    OpenAIRE

    Gerritsen, Lotte; Tendolkar, Indira; Franke, Barbara; Arias Vasquez, Alejandro; Kooijman, Sabine; Buitelaar, Jan; Fernández, Guillén; Rijpkema, Mark

    2011-01-01

    Abstract According to the neurotrophic hypothesis of depression, stress can lead to brain atrophy by modifying brain-derived neurotrophic factor (BDNF) levels. Given that BDNF secretion is affected by a common polymorphism (rs6265, Val66Met), which also is associated with depression, we investigated whether this polymorphism modifies the effect of childhood adversity (CA) on local gray matter volume in depression-relevant brain regions using data from two large cohorts of healthy s...

  5. Neural Tube Defects

    Science.gov (United States)

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the first month ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In spina bifida, ...

  6. The diabetic phenotype is conserved in myotubes established from diabetic subjects: evidence for primary defects in glucose transport and glycogen synthase activity

    DEFF Research Database (Denmark)

    Gaster, Michael; Petersen, Ingrid; Højlund, Kurt;

    2002-01-01

    (GS) activity; the content of glucose-6-phosphate, glucose, and glycogen; and the glucose transport in satellite cell cultures established from diabetic and control subjects. Myotubes were precultured in increasing insulin concentrations for 4 days and subsequently stimulated acutely by insulin. The...... present study shows that the basal glucose uptake as well as insulin-stimulated GS activity is reduced in satellite cell cultures established from patients with type 2 diabetes. Moreover, increasing insulin concentrations could compensate for the reduced GS activity to a certain extent, whereas chronic...

  7. Effects of ganoderic acids on epileptiform discharge hippocampal neurons: insights from alterations of BDNF,TRPC3 and apoptosis.

    Science.gov (United States)

    Yang, Zhi-wei; Wu, Fei; Zhang, Sheng-Li

    2016-06-01

    Recently, Ganoderma lucidum spores (GLS) have shown anti-epileptic effects. However, there are no reports on the anti-epileptic effects of its chemical constituents ganoderic acids (GAs), and more research is needed to better understand the mechanism of GLS activity. In this work, rat primary hippocampal neurons in an in vitro model were used to assess the intervention effects of GAs on epileptiform discharge hippocampal neurons and expression of both BDNF and TRPC3, with the aid of immunofluorescence, MTT method and flow cytometry. It was found that BDNF and TRPC3 are expressed in all cells and were mainly localized in the cytoplasm. The fluorescence intensities of BDNF and TRPC3 in GAs groups were higher than those of normal control and model groups, especially at 80 μg/ml (P < 0.05). The apoptosis rate of neurons was inversely proportional to BDNF and TRPC3 changes (P < 0.01). Therefore, BDNF and TRPC3 should be involved in the occurrence and development of epilepsy. GAs might indirectly inhibit mossy fiber sprouting and adjust the synaptic reconstructions by promoting the expression of BDNF and TRPC3. Besides, GAs could exert a protective effect on hippocampal neurons by promoting neuronal survival and the recovery of injured neurons. PMID:27455554

  8. Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms

    Directory of Open Access Journals (Sweden)

    Kirk I Erickson

    2008-09-01

    Full Text Available Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT and brain-derived neurotrophic factor (BDNF were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single-nucleotide polymorphism (SNP in the COMT (Val158/108Met gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.

  9. Is BDNF sufficient for information transfer between microglia and dorsal horn neurons during the onset of central sensitization?

    Directory of Open Access Journals (Sweden)

    Balasubramanyan Sridhar

    2010-07-01

    Full Text Available Abstract Peripheral nerve injury activates spinal microglia. This leads to enduring changes in the properties of dorsal horn neurons that initiate central sensitization and the onset of neuropathic pain. Although a variety of neuropeptides, cytokines, chemokines and neurotransmitters have been implicated at various points in this process, it is possible that much of the information transfer between activated microglia and neurons, at least in this context, may be explicable in terms of the actions of brain derived neurotrophic factor (BDNF. Microglial-derived BDNF mediates central sensitization in lamina I by attenuating inhibitory synaptic transmission. This involves an alteration in the chloride equilibrium potential as a result of down regulation of the potassium-chloride exporter, KCC2. In lamina II, BDNF duplicates many aspects of the effects of chronic constriction injury (CCI of the sciatic nerve on excitatory transmission. It mediates an increase in synaptic drive to putative excitatory neurons whilst reducing that to inhibitory neurons. CCI produces a specific pattern of changes in excitatory synaptic transmission to tonic, delay, phasic, transient and irregular neurons. A very similar 'injury footprint' is seen following long-term exposure to BDNF. This review presents new information on the action of BDNF and CCI on lamina II neurons, including the similarity of their actions on the kinetics and distributions of subpopulations of miniature excitatory postsynaptic currents (mEPSC. These findings raise the possibility that BDNF functions as a final common path for a convergence of perturbations that culminate in the generation of neuropathic pain.

  10. Correlation between hedgehog (hh) protein family and brain-derived neurotrophic factor (bdnf) in autism spectrum disorder (asd)

    International Nuclear Information System (INIS)

    To determine the correlation of Sonic Hedgehog (SHH), Indian Hedgehog (IHH), and Brain-Derived Neurotrophic Factor (BDNF) in children with Autism Spectrum Disorder (ASD). Study Design: An observational, comparative study. Place and Duration of Study: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2011 to May 2012. Methodology: Serum levels of SHH, IHH and BDNF were determined in recently diagnosed autistic patients and age matched healthy children (n=25), using the Enzyme-Linked Immunosorbent Assay (ELISA). Childhood Autism Rating Scale (CARS) was used for the assessment of autistic severity. Spearman correlation co-efficient-r was determined. Results: The serum levels of IHH and SHH were significantly higher in autistic subjects than those of control subjects. There was significant correlation between age and IHH (r = 0.176, p = 0.03), BDNF and severe IHH (r = 0.1763, p = 0.003), and severe BDNF and severe SHH (r = 0.143, p < 0.001). However, there were no significant relationships among the serum levels of SHH, IHH and BDNF and the CARS score, age or gender. Conclusion: The findings support a correlation between SHH, IHH and BDNF in autistic children, suggesting their pathological role in autism. (author)

  11. Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression

    Directory of Open Access Journals (Sweden)

    Mauricio Schüler Nin

    2011-11-01

    Full Text Available The pharmacological action of SSRI antidepressants may include a normalization of the decreased brain levels of neurosteroids such as that of the progesterone metabolite allopregnanolone and that of the brain-derived neurotrophic factor (BDNF, which are decreased in patients with depression and PTSD. Allopregnanolone and BDNF decrease in these patients is associated with behavioral symptom severity. Antidepressant treatment upregulates both allopregnanolone levels and the expression of BDNF in a manner that significantly correlates with improved symptomatology, which suggests that neurosteroid biosynthesis and BDNF expression may be interrelated. Preclinical studies using the socially isolated mouse as an animal model of behavioral deficits that resemble some of the symptoms observed in PTSD patients have shown that fluoxetine and derivatives improve anxiety-like behavior, fear responses, and aggressive behavior by elevating the corticolimbic levels of allopregnanolone and BDNF mRNA expression. These actions appeared to be independent and more selective from the action of these drugs on 5-HT reuptake inhibition.Hence, this review addresses the hypothesis that in PTSD or depressed patients brain allopregnanolone levels and BDNF expression upregulation may be part of the mechanisms involved in the beneficial actions of antidepressants or other selective brain steroidogenic stimulant (SBSS molecules.

  12. Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK-801 Administration

    Directory of Open Access Journals (Sweden)

    Chunmei Guo

    2010-01-01

    Full Text Available Neonatal blockade of N-methyl-D-aspartic acid (NMDA receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND 5 through 14. Open-field test was performed on PND 42, and PND 77 to examine the validity of the current model. BDNF protein levels in hippocampus and prefrontal cortex (PFC were analyzed on PND 15, PND 42, and PND 77. Results showed that neonatal challenge with MK-801 persistently elevated locomotor activity as well as BDNF expression; the alterations in BDNF expression varied at different developing stages and among brain regions. However, these findings provide neurochemical evidence that the blockade of NMDA receptors during brain development results in long-lasting alterations in BDNF expression and might contribute to neurobehavioral pathology of the present animal model for schizophrenia. Further study in the mechanisms and roles of the BDNF may lead to better understanding of the pathophysiology of schizophrenia.

  13. Brain derived neurotrophic factor gene (BDNF) and personality traits: the modifying effect of season of birth and sex.

    Science.gov (United States)

    Kazantseva, A; Gaysina, D; Kutlumbetova, Yu; Kanzafarova, R; Malykh, S; Lobaskova, M; Khusnutdinova, E

    2015-01-01

    Personality traits are complex phenotypes influenced by interactions of multiple genetic variants of small effect and environmental factors. It has been suggested that the brain derived neurotrophic factor gene (BDNF) is involved in personality traits. Season of birth (SOB) has also been shown to affect personality traits due to its influences on brain development during prenatal and early postnatal periods. The present study aimed to investigate the effects of BDNF on personality traits; and the modifying effects of SOB and sex on associations between BDNF and personality traits. A sample of 1018 young adults (68% women; age range 17-25years) of Caucasian origin from the Russian Federation was assessed on personality traits (Novelty Seeking, Harm Avoidance, Reward Dependence, Persistence, Self-directedness, Cooperativeness, Self-transcendence) with the Temperament and Character Inventory-125 (TCI-125). Associations between personality traits and 12 BDNF SNPs were tested using linear regression models. The present study demonstrated the effect of rs11030102 on Persistence in females only (PFDR=0.043; r(2)=1.3%). There were significant interaction effects between Val66Met (rs6265) and SOB (PFDR=0.048, r(2)=1.4%), and between rs2030323 and SOB (PFDR=0.042, r(2)=1.3%), on Harm Avoidance. Our findings provide evidence for the modifying effect of SOB on the association between BDNF and Harm Avoidance, and for the modifying effect of sex on the association between BDNF and Persistence. PMID:25132151

  14. Methylation of BDNF in women with bulimic eating syndromes: associations with childhood abuse and borderline personality disorder.

    Science.gov (United States)

    Thaler, Lea; Gauvin, Lise; Joober, Ridha; Groleau, Patricia; de Guzman, Rosherrie; Ambalavanan, Amirthagowri; Israel, Mimi; Wilson, Samantha; Steiger, Howard

    2014-10-01

    DNA methylation allows for the environmental regulation of gene expression and is believed to link environmental stressors to such mental-illness phenotypes as eating disorders. Numerous studies have shown an association between bulimia nervosa (BN) and variations in brain-derived neurotrophic factor (BDNF). BDNF has also been linked to borderline personality disorder (BPD) and to such traits as reward dependence. We examined the extent to which BDNF methylation corresponded to bulimic or normal-eater status, and also to the presence of comorbid borderline personality disorder (BPD) and childhood abuse. Our sample consisted of 64 women with BN and 32 normal-eater (NE) control women. Participants were assessed for eating-disorder symptoms, comorbid psychopathology, and childhood trauma, and then they were required to provide blood samples for methylation analyses. We observed a significant site×group (BN vs. NE) interaction indicating that women with BN showed increases in methylation at specific regions of the BDNF promoter. Furthermore, examining effects of childhood abuse and BPD, we observed significant site×group interactions such that groups composed of individuals with childhood abuse or BPD had particularly high levels of methylation at selected CpG sites. Our findings suggest that BN, especially when co-occurring with childhood abuse or BPD, is associated with a propensity towards elevated methylation at specific BDNF promoter region sites. These findings imply that hypermethylation of the BDNF gene may be related to eating disorder status, developmental stress exposure, and comorbid psychopathology. PMID:24801751

  15. BDNF-induced LTP is associated with rapid Arc/Arg3.1-dependent enhancement in adult hippocampal neurogenesis.

    Science.gov (United States)

    Kuipers, Sjoukje D; Trentani, Andrea; Tiron, Adrian; Mao, Xiaosong; Kuhl, Dietmar; Bramham, Clive R

    2016-01-01

    Adult neurogenesis in the hippocampus is a remarkable phenomenon involved in various aspects of learning and memory as well as disease pathophysiology. Brain-derived neurotrophic factor (BDNF) represents a major player in the regulation of this unique form of neuroplasticity, yet the mechanisms underlying its pro-neurogenic actions remain unclear. Here, we examined the effects associated with brief (25 min), unilateral infusion of BDNF in the rat dentate gyrus. Acute BDNF infusion induced long-term potentiation (LTP) of medial perforant path-evoked synaptic transmission and, concomitantly, enhanced hippocampal neurogenesis bilaterally, reflected by increased dentate gyrus BrdU + cell numbers. Importantly, inhibition of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) translation through local, unilateral infusion of anti-sense oligodeoxynucleotides (ArcAS) prior to BDNF infusion blocked both BDNF-LTP induction and the associated pro-neurogenic effects. Notably, basal rates of proliferation and newborn cell survival were unaltered in homozygous Arc/Arg3.1 knockout mice. Taken together these findings link the pro-neurogenic effects of acute BDNF infusion to induction of Arc/Arg3.1-dependent LTP in the adult rodent dentate gyrus. PMID:26888068

  16. Substitution and defect chemistry of La-Cu-O systems

    International Nuclear Information System (INIS)

    In this paper substitutional effects of strontium in La-Cu-O system and defects accommodating stoichiometric deviations is investigated. The extended shear defects are analyzed using electron microscopy and the role in superconducting transport properties has been examined by magnetic measurements. The initial results suggest that the defects enhance flux pinning

  17. BDNF and Schizophrenia: from Neurodevelopment to Neuronal Plasticity, Learning and Memory.

    Directory of Open Access Journals (Sweden)

    RodrigoNieto

    2013-06-01

    Full Text Available Brain Derived Neurotrophic Factor (BDNF is a neurotrophin that has been related not only to neurodevelopment and neuroprotection, but also to synapse regulation, learning and memory. Research focused on the neurobiology of schizophrenia has emphasized the relevance of neurodevelompental and neurotoxicity-related elements in the pathogenesis of this disease. Research focused on the clinical features of schizophrenia in the past decades has emphasized the relevance of cognitive deficits of this illness, considered a core manifestation and an important predictor for functional outcome. Variations in neurotrophins such as BDNF may have a role as part of the molecular mechanisms underlying these processes, from the neurodevelopmental alterations to the molecular mechanisms of cognitive dysfunction in patients with schizophrenia.

  18. Social defeat during adolescence and adulthood differentially induce BDNF-regulated immediate early genes

    Directory of Open Access Journals (Sweden)

    Caroline M. Coppens

    2011-11-01

    Full Text Available Stressful life events generally enhance the vulnerability for the development of human psychopathologies such as anxiety disorders and depression. The incidence rates of adult mental disorders steeply rises during adolescence in parallel with a structural and functional reorganization of the neural circuitry underlying stress reactivity. However, the mechanisms underlying susceptibility to stress and manifestation of mental disorders during adolescence are little understood. We hypothesized that heightened sensitivity to stress during adolescence reflects age-dependent differences in the expression of activity-dependent genes involved in synaptic plasticity. Therefore, we compared the effect of social stress during adolescence with social stress in adulthood on the expression of a panel of genes linked to induction of long-term potentiation (LTP and brain-derived neurotrophic factor (BDNF signaling. We show that social defeat during adolescence and adulthood differentially regulates expression of the immediate early genes BDNF, Arc, Carp, and Tieg1, as measured by qPCR in tissue lysates from prefrontal cortex, nucleus accumbens, and hippocampus. In the hippocampus, mRNA levels for all four genes were robustly elevated following social defeat in adolescence, whereas none were induced by defeat in adulthood. The relationship to coping style was also examined using adult reactive and proactive coping rats. Gene expression levels of reactive and proactive animals were similar in the prefrontal cortex and hippocampus. However, a trend toward a differential expression of BDNF and Arc mRNA in the nucleus accumbens was detected. BDNF mRNA was increased in the nucleus accumbens of proactive defeated animals, whereas the expression level in reactive defeated animals was comparable to control animals. The results demonstrate striking differences in immediate early gene expression in response to social defeat in adolescent and adult rats.

  19. Continuous Brain-derived Neurotrophic Factor (BDNF) Infusion After Methylprednisolone Treatment in Severe Spinal Cord Injury

    OpenAIRE

    Kim, Daniel H.; Jahng, Tae-Ahn

    2004-01-01

    Although methylprednisolone (MP) is the standard of care in acute spinal cord injury (SCI), its functional outcome varies in clinical situation. Recent report demonstrated that MP depresses the expression of growth-promoting neurotrophic factors after acute SCI. The present study was designed to investigate whether continuous infusion of brain-derived neurotrophic factor (BDNF) after MP treatment promotes functional recovery in severe SCI. Contusion injury was produced at the T10 vertebral le...

  20. Motoneuron BDNF/TrkB Signaling Enhances Functional Recovery after Cervical Spinal Cord Injury

    OpenAIRE

    Mantilla, Carlos B.; Gransee, Heather M.; Zhan, Wen-Zhi; Sieck, Gary C.

    2013-01-01

    A C2 cervical spinal cord hemisection (SH) interrupts descending inspiratory-related drive to phrenic motoneurons located between C3 and C5 in rats, paralyzing the ipsilateral hemidiaphragm muscle. There is gradual recovery of rhythmic diaphragm muscle activity ipsilateral to cervical spinal cord injury over time, consistent with neuroplasticity and strengthening of spared, contralateral descending premotor input to phrenic motoneurons. Brainderived neurotrophic factor (BDNF) signaling throug...

  1. Expression and localisation of BDNF, NT4 and TrkB in proliferative vitreoretinopathy.

    Science.gov (United States)

    Ghazi-Nouri, Seyed M S; Ellis, James S; Moss, Stephen; Limb, G Astrid; Charteris, David G

    2008-05-01

    Exogenous brain derived neurotrophic factor (BDNF) is known to rescue ganglion cell death after optic nerve injury. Its mechanism of action is believed to be indirect via glial cells in the retina. In this study we investigated the changes in expression and localisation of BDNF, neurotrophin-4 (NT4) and their common receptor (TrkB) in retinectomy sections of patients with proliferative vitreoretinopathy (PVR). Nine full-thickness retinectomy specimens obtained at retinal reattachment surgery for PVR were fixed in 4% paraformaldehyde immediately after excision and compared to similarly processed normal donor retinas (4 eyes). Agarose-embedded sections (100 microm thick) were double labelled for immunohistochemistry by confocal microscopy, with antibodies against BDNF, NT4, TrkB, rod opsin, glial fibrillary acidic protein (GFAP), cellular retinaldehyde binding protein (CRALBP) and Brn3. This study demonstrates expression of NT4 by ganglion cells and shows expression of BDNF and NT4 in the outer photoreceptor segments is downregulated during PVR, whilst NT4 is markedly upregulated throughout the retina during this condition. The findings here suggest that NT4 may play a neural protective role during the development of PVR. It also shows that upregulation of NT4 in PVR is localised to Müller glial cells, indicating either over-expression of this factor by Müller cells or that Müller cells internalise NT4 for trafficking across the retina. TrkB expression was not observed in PVR retina. The observations that Müller glia demonstrate upregulation of NT4 suggests that retinal injury may lead to activation of this neurotrophin by Müller cells as part of their neuroprotective functions. PMID:18405896

  2. Age-related changes in plasma levels of BDNF in Down syndrome patients

    OpenAIRE

    Licastro Federico; Galliera Emanuela; Dogliotti Giada; Corsi Massimiliano M

    2010-01-01

    Abstract Background The prevalence of coronary artery diseases is low among Down Syndrome (DS) patients and they rarely die of atherosclerotic complications. Histopathological investigations showed no increase in atherosclerosis, or even a total lack of atherosclerotic changes, in DS Aim The aim of our study is to investigate the relationship between age and brain-derived neurotrophic factor (BDNF) levels in Down Syndrome (DS). Subjects and methods Three groups of DS patients were studied: th...

  3. BDNF–TrkB signaling as a therapeutic target in neuropsychiatric disorders

    OpenAIRE

    Hill, R. Anne

    2014-01-01

    Xin Du,1 Yeewen C Wu,1,2 Rachel Anne Hill1 1Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia; 2Department of Pharmacology, University of Melbourne, Parkville, VIC, Australia Abstract: Research evidence points to abnormal brain-derived neurotrophic factor (BDNF) signaling being a common and vital participant in the etiology and pathophysiology of many psychiatric disorders, including depression, schizophrenia, and bipolar disorder. To inc...

  4. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

    Science.gov (United States)

    Jasińska, Kaja K; Molfese, Peter J; Kornilov, Sergey A; Mencl, W Einar; Frost, Stephen J; Lee, Maria; Pugh, Kenneth R; Grigorenko, Elena L; Landi, Nicole

    2016-01-01

    Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes. PMID:27551971

  5. Association Study between BDNF Gene Polymorphisms and Autism by Three-Dimensional Gel-Based Microarray

    OpenAIRE

    Zuhong Lu; Yunfei Bai; Xiaoyan Ke; Beili Sun; Lu Cheng; Pengfeng Xiao; Qinyu Ge

    2009-01-01

    Single nucleotide polymorphisms (SNPs) are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four ...

  6. Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice

    OpenAIRE

    Chen, Jieli; Zhang, Chunling; Jiang, Hao; Li, Yi; Zhang, Lijie; Robin, Adam; Katakowski, Mark; Lu, Mei; Chopp, Michael

    2005-01-01

    Molecular mechanisms underlying the role of statins in the induction of brain plasticity and subsequent improvement of neurologic outcome after treatment of stroke have not been adequately investigated. Here, we use both in vivo and in vitro studies to investigate the potential roles of two prominent factors, vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF), in mediating brain plasticity after treatment of stroke with atorvastatin. Treatment of stroke in ...

  7. Chronic lipopolysaccharide exposure induces cognitive dysfunction without affecting BDNF expression in the rat hippocampus

    OpenAIRE

    Zhu, Bin; Wang, Zhi-Gang; Ding, Jie; Liu, Ning; WANG Da-ming; Ding, Liang-cai; YANG, CHUN

    2014-01-01

    Previous studies have shown that lipopolysaccharide (LPS) has the potential to cause cognitive dysfunction. However, the underlying pathogenesis has yet to be fully elucidated. Increasing attention is being focused on infection in the central nervous system. Therefore, the present study aimed to investigate the behavioral performance of rats receiving intraperitoneal injections of LPS and to determine the expression levels of amyloid-β (Aβ), brain-derived neurotrophic factor (BDNF) and pro-in...

  8. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males

    OpenAIRE

    WARMINGTON, STUART; O'Mara, Shane; GRIFFIN, EADAOIN; KELLY, AINE

    2011-01-01

    PUBLISHED Physical activity has been reported to improve cognitive function in humans and rodents, possibly via a brain-derived neurotrophic factor (BDNF)-regulated mechanism. In this study of human subjects, we have assessed the effects of acute and chronic exercise on performance of a face-name matching task, which recruits the hippocampus and associated structures of the medial temporal lobe, and the Stroop word-colour task, which does not, and have assessed circulating concentrations o...

  9. Association between BDNF rs6265 and Obesity in the Boston Puerto Rican Health Study

    Directory of Open Access Journals (Sweden)

    Xian-Yong Ma

    2012-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF has been associated with regulation of body weight and appetite. The goal of this study was to examine the interactions of a functional variant (rs6265 in the BDNF gene with dietary intake for obesity traits in the Boston Puerto Rican Health Study. BDNF rs6265 was genotyped in 1147 Puerto Rican adults and examined for association with obesity-related traits. Men (n=242 with the GG genotype had higher BMI (P=0.009, waist circumference (P=0.002, hip (P=0.002, and weight (P=0.03 than GA or AA carriers (n=94. They had twice the risk of being overweight (BMI≥25 relative to GA or AA carriers (OR = 2.08, CI = 1.02–4.23, and P=0.043. Interactions between rs6265 and polyunsaturated fatty acids (PUFA intake were associated with BMI, hip, and weight, and n-3 : n-6 PUFA ratio with waist circumference in men. In contrast, women (n=595 with the GG genotype had significantly lower BMI (P=0.009, hip (P=0.029, and weight (P=0.027 than GA or AA carriers (n=216. Women with the GG genotype were 50% less likely to be overweight compared to GA or AA carriers (OR = 0.05, CI = 0.27–0.91, and P=0.024. In summary, BDNF rs6265 is differentially associated with obesity risk by sex and interacts with PUFA intake influencing obesity traits in Boston Puerto Rican men.

  10. Mood Disorders and BDNF Relationship with Alcohol Drinking Trajectories among PLWH Receiving Care

    OpenAIRE

    Míguez-Burbano, María José; Espinoza, Luis; Vargas, Mayra; LaForest, Diana

    2014-01-01

    Background Despite the excessive rates of Hazardous Alcohol Use (HAU) among people living with HIV (PLWH), although largely speculated, psychological and physiological components associated with HAU, has not been actively measured. Therefore, the present study was geared toward determining: 1) the rates of mood disorders and its relationship with HAU, and 2) to assess the impact of Brain Derived Neurotrophic Factor (BDNF), a well-known regulator of alcohol and mood disorders. Methods For this...

  11. Reduced cortical BDNF expression and aberrant memory in Carf knockout mice

    OpenAIRE

    McDowell, Kelli A.; Hutchinson, Ashley N.; Wong-Goodrich, Sarah J.E.; Presby, Matthew M.; Su, Dan; Rodriguiz, Ramona M.; Law, Krystal C.; Williams, Christina L.; Wetsel, William C.; West, Anne E.

    2010-01-01

    Transcription factors are a key point of convergence between the cell-intrinsic and extracellular signals that guide synaptic development and brain plasticity. Calcium-Response Factor (CaRF) is a unique transcription factor first identified as a binding protein for a calcium-response element in the gene encoding Brain-Derived Neurotrophic Factor (Bdnf). We have now generated Carf knockout (KO) mice to characterize the function of this factor in vivo. Intriguingly, Carf KO mice have selectivel...

  12. Functional and structural specific roles of activity-driven BDNF within circuits formed by single spiny stellate neurons of the barrel cortex

    Directory of Open Access Journals (Sweden)

    Qian-Quan eSun

    2014-11-01

    Full Text Available Brain derived neurotrophic factor (BDNF plays key roles in several neurodevelopmental disorders and actions of pharmacological treatments. However it is uncealr how specific BDNF’s effects are on diffeerent circuit components. Current studies have largely focused on the role of BDNF in modification of synaptic development. The precise roles of BDNF in the refinement of a functional circuit in vivo remain unclear. Val66Met polymorphism of BDNF may be associated with increased risk for cognitive impairments and is mediated at least in part by activity-dependent trafficking and/or secretion of BDNF. Using mutant mice that lacked activity-driven BDNF expression (bdnf-KIV, we previously reported that experience regulation of the cortical GABAergic network is mediated by activity-driven BDNF expression. Here, we demonstrate that activity-driven BDNF’s effects on circuits formed by the layer IV spiny stellate cells are highly specific. Structurally, dendritic but not axonal morphology was altered in the mutant. Physiologically, GABAergic but not glutamatergic synapses were severely affected. The effects on GABA transmission occurs via presynaptic alteration of calcium-dependent release probability. These results suggest that neuronal activity through activity-driven BDNF expression, can selectively regulate specific features of layer IV circuits in vivo. We postulate that the role of activity-dependent BDNF is to modulate the computational ability of circuits that relate to the gain control (i.e. feed-forward inhibition; whereas the basic wiring of circuits relevant to the sensory pathway is spared. Gain control modulation within cortical circuits has broad impact on cognitive processing and brain state-transitions. Cognitive behavior and mode is determined by brain states, thus the studying of circuit alteration by endogenous BDNF provides insights into the cellular and molecular mechanisms of diseases mediated by BDNF.

  13. Differential Expression and Regulation of Brain-Derived Neurotrophic Factor (BDNF) mRNA Isoforms in Brain Cells from Mecp2(308/y) Mouse Model.

    Science.gov (United States)

    Rousseaud, Audrey; Delépine, Chloé; Nectoux, Juliette; Billuart, Pierre; Bienvenu, Thierry

    2015-08-01

    Rett syndrome (RTT) is a severe neurodevelopmental disease caused by mutations in methyl-CpG-binding protein 2 (MECP2), which encodes a transcriptional modulator of many genes including BDNF. BDNF comprises nine distinct promoter regions, each triggering the expression of a specific transcript. The role of this diversity of transcripts remains unknown. MeCP2 being highly expressed in neurons, RTT was initially considered as a neuronal disease. However, recent studies have shown that MeCP2 was also expressed in astrocytes. Though several studies explored Bdnf IV expression in Mecp2-deficient mice, the differential expression of Bdnf isoforms in Mecp2-deficient neurons and astrocytes was never studied. By using TaqMan technology and a mouse model expressing a truncated Mecp2 (Mecp2(308/y)), we firstly showed in neurons that Bdnf transcripts containing exon I, IIb, IIc, IV, and VI are prominently expressed, whereas in astrocytes, Bdnf transcript containing exon VI is preferentially expressed, suggesting a specific regulation of Bdnf expression at the cellular level. Secondly, we confirmed the repressive role of Mecp2 only on the expression of Bdnf VI in neurons. Our data suggested that the truncated Mecp2 protein maintains its function on Bdnf expression regulation in neurons and in astrocytes. Interestingly, we observed that Bdnf transcripts (I and IXA), regulated by neural activity induced by bicuculline in Mecp2(308/y) neurons, were not affected by histone deacetylase inhibition. In contrast, Bdnf transcripts (IIb, IIc, and VI), regulated by histone deacetylation, were not affected by bicuculline treatment in wild-type and Mecp2(308/y) neurons. All these results reflect the complexity of regulation of Bdnf gene. PMID:25634725

  14. INTERMITTENT SOCIAL DEFEAT STRESS ENHANCES MESOCORTICOLIMBIC ΔFOSB/BDNF CO-EXPRESSION AND PERSISTENTLY ACTIVATES CORTICOTEGMENTAL NEURONS: IMPLICATION FOR VULNERABILITY TO PSYCHOSTIMULANTS

    OpenAIRE

    Nikulina, E.M.; Lacagnina, M.J.; Fanous, S.; Wang, J.; Hammer, R P

    2012-01-01

    Intermittent social defeat stress exposure augments behavioral response to psychostimulants in a process termed cross-sensitization. Brain-derived neurotrophic factor (BDNF) mediates synaptic plasticity and cellular responses to stress and drugs of abuse. We previously showed that repeated social defeat stress persistently alters BDNF and activates ΔFosB expression in mesocorticolimbic regions. Here, we hypothesized that social defeat stress would increase ΔFosB expression in BDNF-containing ...

  15. The Association of BDNF Gene Variants with Behaviour Traits in Sika Deer (Cervus nippon)

    OpenAIRE

    Wei Wan-Hong; Guo Jun; Yang Yan; Lv Shen-Jin

    2011-01-01

    It is widely accepted that Brain Derived Neurotrophic Factor (BDNF) is involved in modulating behaviour performance induced by environmental conditions. The aim of this study was to study polymorphisms of the BDNF gene and their relationship with animal behaviour in sika deer (Cervus nippon). About 48 sika deer reared under Ping-Shan-Tang Farm (25 deers) and Zhu-Yu-Wan Park (23 deers), Yangzhou City, Jiangsu province, China were observed and blood samples taken to identify BDNF genotypes. Dat...

  16. Low-Level Stress Induces Production of Neuroprotective Factors in Wild-Type but Not BDNF+/- Mice: Interleukin-10 and Kynurenic Acid

    OpenAIRE

    Dugan, Allison M.; Parrott, Jennifer M.; Redus, Laney; Hensler, Julie G.; O’Connor, Jason C.

    2015-01-01

    Background: Brain-derived neurotrophic factor (BDNF) deficiency confers vulnerability to stress, but the mechanisms are unclear. BDNF+/- mice exhibit behavioral, physiological, and neurochemical changes following low-level stress that are hallmarks of major depression. After immune challenge, neuroinflammation-induced changes in tryptophan metabolism along the kynurenine pathway mediate depressive-like behaviors. Methods: We hypothesized that BDNF+/- mice would be more susceptible to stress-i...

  17. Demethylation regulation of BDNF gene expression in dorsal root ganglion neurons is implicated in opioid-induced pain hypersensitivity in rats.

    Science.gov (United States)

    Chao, Yu-Chieh; Xie, Fang; Li, Xueyang; Guo, Ruijuan; Yang, Ning; Zhang, Chen; Shi, Rong; Guan, Yun; Yue, Yun; Wang, Yun

    2016-07-01

    Repeated administration of morphine may result in opioid-induced hypersensitivity (OIH), which involves altered expression of numerous genes, including brain-derived neurotrophic factor (BDNF) in dorsal root ganglion (DRG) neurons. Yet, it remains unclear how BDNF expression is increased in DRG neurons after repeated morphine treatment. DNA methylation is an important mechanism of epigenetic control of gene expression. In the current study, we hypothesized that the demethylation regulation of certain BDNF gene promoters in DRG neurons may contribute to the development of OIH. Real-time RT-PCR was used to assess changes in the mRNA transcription levels of major BDNF exons including exon I, II, IV, VI, as well as total BDNF mRNA in DRGs from rats after repeated morphine administration. The levels of exon IV and total BDNF mRNA were significantly upregulated by repeated morphine administration, as compared to that in saline control group. Further, ELISA array and immunocytochemistry study revealed a robust upregulation of BDNF protein expression in DRG neurons after repeated morphine exposure. Correspondingly, the methylation levels of BDNF exon IV promoter showed a significant downregulation by morphine treatment. Importantly, intrathecal administration of a BDNF antibody, but not control IgG, significantly inhibited mechanical hypersensitivity that developed in rats after repeated morphine treatment. Conversely, intrathecal administration of an inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-aza-dC) markedly upregulated the BDNF protein expression in DRG neurons and enhanced the mechanical allodynia after repeated morphine exposure. Together, our findings suggest that demethylation regulation of BDNF gene promoter may be implicated in the development of OIH through epigenetic control of BDNF expression in DRG neurons. PMID:26970395

  18. Cognitive Impairment in Schizophrenia: Interplay of BDNF and Childhood Trauma? A Review of Literature.

    Science.gov (United States)

    Sahu, Geetanjali; Malavade, Kishor; Jacob, Theresa

    2016-09-01

    Cognitive impairment is a core feature of schizophrenia. These deficits can also serve as an endophenotype for the illness in genetic studies. There is evidence that suggests that cognition can be considered a reasonable target for intervention in both schizophrenia and bipolar disorder. One of the most studied genetic phenotypes for psychosis is brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms. BDNF has an established role in neuronal development and cell survival in response to stress and is abnormally expressed in schizophrenia. Studies have shown that childhood trauma is associated with poor prognosis of schizophrenic patients. BDNF-Val66Met polymorphism has been shown to moderate the impact of childhood adversity on later expression of affective symptoms, suggesting the possibility of gene environment interactions. Considering the recent advances of neuroscience an up to date review of relevant literature is warranted in this field. This article reviews the current literature available regarding associations between the Val66Met polymorphism, childhood trauma and cognitive dysfunction in schizophrenia. PMID:26603624

  19. Deep brain stimulation of the ventral striatum increases BDNF in the fear extinction circuit

    Directory of Open Access Journals (Sweden)

    Fabricio H Do-Monte

    2013-08-01

    Full Text Available Deep brain stimulation (DBS of the ventral capsule/ventral striatum (VC/VS reduces the symptoms of treatment-resistant obsessive compulsive disorder (OCD, and improves response to extinction-based therapies. We recently reported that DBS-like stimulation of a rat homologue of VC/VS, the dorsal-VS, reduced conditioned fear and enhanced extinction memory (Rodriguez-Romaguera et al, 2012. In contrast, DBS of the ventral-VS had the opposite effects. To examine possible mechanisms, we assessed the effects of VS DBS on the expression of the neural activity marker Fos and brain-derived neurotrophic factor (BDNF, a key mediator of extinction plasticity in prefrontal-amygdala circuits. Consistent with decreased fear expression, DBS of dorsal-VS increased Fos expression in prelimbic and infralimbic prefrontal cortices and in the lateral division of the central nucleus of amygdala, an area that inhibits amygdala output. Consistent with improved extinction memory, we found that DBS of dorsal-VS, but not ventral-VS, increased neuronal BDNF expression in prelimbic and infralimbic prefrontal cortices. These rodent findings are consistent with the idea that clinical DBS of VC/VS may augment fear extinction through an increase in BDNF expression.

  20. Deep brain stimulation of the ventral striatum increases BDNF in the fear extinction circuit.

    Science.gov (United States)

    Do-Monte, Fabricio H; Rodriguez-Romaguera, Jose; Rosas-Vidal, Luis E; Quirk, Gregory J

    2013-01-01

    Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces the symptoms of treatment-resistant obsessive compulsive disorder (OCD), and improves response to extinction-based therapies. We recently reported that DBS-like stimulation of a rat homologue of VC/VS, the dorsal-VS, reduced conditioned fear and enhanced extinction memory (Rodriguez-Romaguera et al., 2012). In contrast, DBS of the ventral-VS had the opposite effects. To examine possible mechanisms of these effects, we assessed the effects of VS DBS on the expression of the neural activity marker Fos and brain-derived neurotrophic factor (BDNF), a key mediator of extinction plasticity in prefrontal-amygdala circuits. Consistent with decreased fear expression, DBS of dorsal-VS increased Fos expression in prelimbic and infralimbic prefrontal cortices and in the lateral division of the central nucleus of amygdala, an area that inhibits amygdala output. Consistent with improved extinction memory, we found that DBS of dorsal-VS, but not ventral-VS, increased neuronal BDNF expression in prelimbic and infralimbic prefrontal cortices. These rodent findings are consistent with the idea that clinical DBS of VC/VS may augment fear extinction through an increase in BDNF expression. PMID:23964215

  1. A selective histone deacetylase-6 inhibitor improves BDNF trafficking in hippocampal neurons from Mecp2 knockout mice:implications for Rett syndrome

    Directory of Open Access Journals (Sweden)

    Xin eXu

    2014-03-01

    Full Text Available Rett syndrome (RTT is a neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2. One of the most prominent gene targets of MeCP2 is brain-derived neurotrophic factor (Bdnf, a potent modulator of activity-dependent synaptic development, function and plasticity. Dysfunctional BDNF signaling has been demonstrated in several pathophysiological mechanisms of RTT disease progression. To evaluate whether the dynamics of BDNF trafficking is affected by Mecp2 deletion, we analyzed movements of BDNF tagged with yellow fluorescent protein (YFP in cultured hippocampal neurons by time-lapse fluorescence imaging. We found that both anterograde and retrograde vesicular trafficking of BDNF-YFP are significantly impaired in Mecp2 knockout hippocampal neurons. Selective inhibitors of histone deacetylase 6 (HDAC6 show neuroprotective effects in neurodegenerative diseases and stimulate microtubule-dependent vesicular trafficking of BDNF-containing dense core vesicles. Here, we show that the selective HDAC6 inhibitor Tubastatin-A increased the velocity of BDNF-YFP vesicles in Mecp2 knockout neurons in both directions by increasing αtubulin acetylation. Tubastatin-A also restored activity-dependent BDNF release from Mecp2 knockout neurons to levels comparable to those shown by wildtype neurons. These findings demonstrate that a selective HDAC6 inhibitor is a potential pharmacological strategy to reverse cellular and synaptic impairments in RTT resulting from impaired BDNF signaling.

  2. Role of accumbens BDNF and TrkB in cocaine-induced psychomotor sensitization, conditioned-place preference, and reinstatement in rats

    OpenAIRE

    Bahi, Amine; Boyer, Frederic; Vijay, Chandrasekar; Dreyer, Jean-Luc

    2008-01-01

    Background Brain-derived neurotrophic factor (BDNF) is involved in the survival and function of midbrain DA neurons. BDNF action is mediated by the TrkB receptor–tyrosine kinase, and both BDNF and TrkB transcripts are widely expressed in the rat mesolimbic pathway, including the nucleus accumbens (NAc) and the ventral tegmentum area (VTA). Objective BDNF was previously shown to be involved in cocaine reward and relapse, as assessed in rat models. The goal of this study is to explore the role ...

  3. 49 CFR 215.121 - Defective car body.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Car Bodies § 215.121 Defective car body. A railroad may not place or continue in service a car, if: (a) Any portion of... 49 Transportation 4 2010-10-01 2010-10-01 false Defective car body. 215.121 Section...

  4. 49 CFR 215.119 - Defective freight car truck.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defective freight car truck. 215.119 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.119 Defective freight car truck. A railroad may not place or continue in service...

  5. The CB₁ cannabinoid receptor signals striatal neuroprotection via a PI3K/Akt/mTORC1/BDNF pathway.

    Science.gov (United States)

    Blázquez, C; Chiarlone, A; Bellocchio, L; Resel, E; Pruunsild, P; García-Rincón, D; Sendtner, M; Timmusk, T; Lutz, B; Galve-Roperh, I; Guzmán, M

    2015-10-01

    The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. In particular, the CB1 receptor is highly expressed in the basal ganglia, mostly on terminals of medium-sized spiny neurons, where it plays a key neuromodulatory function. The CB1 receptor also confers neuroprotection in various experimental models of striatal damage. However, the assessment of the physiological relevance and therapeutic potential of the CB1 receptor in basal ganglia-related diseases is hampered, at least in part, by the lack of knowledge of the precise mechanism of CB1 receptor neuroprotective activity. Here, by using an array of pharmacological, genetic and pharmacogenetic (designer receptor exclusively activated by designer drug) approaches, we show that (1) CB1 receptor engagement protects striatal cells from excitotoxic death via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin complex 1 pathway, which, in turn, (2) induces brain-derived neurotrophic factor (BDNF) expression through the selective activation of BDNF gene promoter IV, an effect that is mediated by multiple transcription factors. To assess the possible functional impact of the CB1/BDNF axis in a neurodegenerative-disease context in vivo, we conducted experiments in the R6/2 mouse, a well-established model of Huntington's disease, in which the CB1 receptor and BDNF are known to be severely downregulated in the dorsolateral striatum. Adeno-associated viral vector-enforced re-expression of the CB1 receptor in the dorsolateral striatum of R6/2 mice allowed the re-expression of BDNF and the concerted rescue of the neuropathological deficits in these animals. Collectively, these findings unravel a molecular link between CB1 receptor activation and BDNF expression, and support the relevance of the CB1/BDNF axis in promoting striatal neuron survival. PMID:25698444

  6. Serum BDNF levels before and after the development of mood disorders: a case-control study in a population cohort.

    Science.gov (United States)

    Ihara, K; Yoshida, H; Jones, P B; Hashizume, M; Suzuki, Y; Ishijima, H; Kim, H K; Suzuki, T; Hachisu, M

    2016-01-01

    Serum levels of brain-derived neurotrophic factor (BDNF) are low in major depressive disorder (MDD), and were recently shown to decrease in chronic depression, but whether this is a trait or state marker of MDD remains unclear. We investigated whether serum BDNF levels decrease before or after the developments of MDD and other mood disorders through a case-control study nested in a cohort of 1276 women aged 75-84 years in 2008. Psychiatrists using the Structured Clinical Interview for DSM-IV identified incident cases of mood disorders at follow-up surveys in 2010 and 2012: 28 of MDDs, 39 of minor depressive disorders (minDDs) and 8 of minor depressive episodes with a history of major depressive episodes (minDEs with MDE history). A total of 106 representative non-depressed controls were also identified in the 2012 follow-up. We assayed BDNF levels in preserved sera of cases and controls at baseline and at follow-up. Serum BDNF levels at baseline in cases of MDD, minDD or minDE with MDE history were no lower than those in controls. The decrease in the serum BDNF level from baseline to follow-up was greater in cases of MDD or minDE with MDE history than in controls or cases of minDD. These results show that serum BDNF levels are not a trait marker of MDD in old women but appeared to be a state marker. The different changes in BDNF levels among diagnostic groups suggest that MDD has a pathophysiologic relation to minDE with MDE history, rather than to minDD. PMID:27070410

  7. Interactive actions of Bdnf methylation and cell metabolism for building neural resilience under the influence of diet.

    Science.gov (United States)

    Tyagi, Ethika; Zhuang, Yumei; Agrawal, Rahul; Ying, Zhe; Gomez-Pinilla, Fernando

    2015-01-01

    Quality nutrition during the period of brain formation is a predictor of brain functional capacity and plasticity during adulthood; however it is not clear how this conferred plasticity imparts long-term neural resilience. Here we report that early exposure to dietary omega-3 fatty acids orchestrates key interactions between metabolic signals and Bdnf methylation creating a reservoir of neuroplasticity that can protect the brain against the deleterious effects of switching to a Western diet (WD). We observed that the switch to a WD increased Bdnf methylation specific to exon IV, in proportion to anxiety-like behavior, in Sprague Dawley rats reared in low omega-3 fatty acid diet, and these effects were abolished by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. Blocking methylation also counteracted the reducing action of WD on the transcription regulator CTCF binding to Bdnf promoter IV. In vitro studies confirmed that CTCF binding to Bdnf promoter IV is essential for the action of DHA on BDNF regulation. Diet is also intrinsically associated to cell metabolism, and here we show that the switch to WD downregulated cell metabolism (NAD/NADH ratio and SIRT1). The fact that DNA methyltransferase inhibitor did not alter these parameters suggests they occur upstream to methylation. In turn, the methylation inhibitor counteracted the action of WD on PGC-1α, a mitochondrial transcription co-activator and BDNF regulator, suggesting that PGC-1α is an effector of Bdnf methylation. Results support a model in which diet can build an "epigenetic memory" during brain formation that confers resilience to metabolic perturbations occurring in adulthood. PMID:25283985

  8. Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X-linked mental retardation in two unrelated Dutch families.

    Science.gov (United States)

    Mancini, G M S; Catsman-Berrevoets, C E; de Coo, I F M; Aarsen, F K; Kamphoven, J H J; Huijmans, J G; Duran, M; van der Knaap, M S; Jakobs, C; Salomons, G S

    2005-01-30

    Four Dutch male patients, two brothers from unrelated families were referred for investigation of psychomotor and severe language/speech delay. All four patients showed growth deficiency over the years. Facial features and poor body habitus were quite similar in the patients and in their mothers. Brain MRI showed nonspecific periventricular white matter lesions. In all the patients neuropsychological tests revealed moderate mental retardation, attention deficit and hyperactivity with impulsivity, a semantic-pragmatic language disorder, and oral dyspraxia. This specific cognitive profile is different from other children with mental retardation syndromes and seems to be unique. Excretion of creatine to creatinine ratio in urine of the four boys was increased compared to controls and their creatine uptake in fibroblasts was deficient. In the two brothers from the first pedigree, DNA sequence analysis revealed a novel mutation in the splice donor site in intron 10 (IVS10 + 5G>C, c.1495 + 5G>C) of the SLC6A8 gene leading to skipping of exon 10. In the other sib pair a novel missense mutation (c. 1361C>T; p.Pro544Leu) was found. These are the first families reported, in which the clinical suspicion of a creatine transporter disorder was raised on clinical grounds, before a brain 1H-MRS suggested the diagnosis. Screening of apparently X-linked mental retarded patients with this somatic and behavioral phenotype by the biochemical assay of creatine to creatinine ratio in the urine or DNA sequence analysis of SLC6A8 is worthwhile even when 1H-MRS is not available. PMID:15690373

  9. Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment.

    Science.gov (United States)

    Rossi, Chiara; Angelucci, Andrea; Costantin, Laura; Braschi, Chiara; Mazzantini, Mario; Babbini, Francesco; Fabbri, Maria Elena; Tessarollo, Lino; Maffei, Lamberto; Berardi, Nicoletta; Caleo, Matteo

    2006-10-01

    Neurogenesis continues to occur in the adult mammalian hippocampus and is regulated by both genetic and environmental factors. It is known that exposure to an enriched environment enhances the number of newly generated neurons in the dentate gyrus. However, the mechanisms by which enriched housing produces these effects are poorly understood. To test a role for neurotrophins, we used heterozygous knockout mice for brain-derived neurotrophic factor (BDNF+/-) and mice lacking neurotrophin-4 (NT-4-/-) together with their wild-type littermates. Mice were either reared in standard laboratory conditions or placed in an enriched environment for 8 weeks. Animals received injections of the mitotic marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild-type and enriched NT-4-/- mice showed a two-fold increase in hippocampal neurogenesis as assessed by stereological counting of BrdU-positive cells in the dentate gyrus and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this enhancement of hippocampal neurogenesis was not seen in enriched BDNF+/- mice. Failure to up-regulate BDNF accompanied the lack of a neurogenic response in enriched BDNF heterozygous mice. We conclude that BDNF but not NT-4 is required for the environmental induction of neurogenesis. PMID:17040481

  10. Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase

    Science.gov (United States)

    Borrell-Pagès, Maria; Canals, Josep M.; Cordelières, Fabrice P.; Parker, J. Alex; Pineda, José R.; Grange, Ghislaine; Bryson, Elzbieta A.; Guillermier, Martine; Hirsch, Etienne; Hantraye, Philippe; Cheetham, Michael E.; Néri, Christian; Alberch, Jordi; Brouillet, Emmanuel; Saudou, Frédéric; Humbert, Sandrine

    2006-01-01

    There is no treatment for the neurodegenerative disorder Huntington disease (HD). Cystamine is a candidate drug; however, the mechanisms by which it operates remain unclear. We show here that cystamine increases levels of the heat shock DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits polyQ-huntingtin–induced death of striatal neurons and neuronal dysfunction in Caenorhabditis elegans. This neuroprotective effect involves stimulation of the secretory pathway through formation of clathrin-coated vesicles containing brain-derived neurotrophic factor (BDNF). Cystamine increases BDNF secretion from the Golgi region that is blocked by reducing HSJ1b levels or by overexpressing transglutaminase. We demonstrate that cysteamine, the FDA-approved reduced form of cystamine, is neuroprotective in HD mice by increasing BDNF levels in brain. Finally, cysteamine increases serum levels of BDNF in mouse and primate models of HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels can be used as a biomarker for drug efficacy. PMID:16604191

  11. Brain BDNF levels elevation induced by physical training is reduced after unilateral common carotid artery occlusion in rats.

    Science.gov (United States)

    Banoujaafar, Hayat; Van Hoecke, Jacques; Mossiat, Claude M; Marie, Christine

    2014-10-01

    We investigated the contribution of blood flow elevation in the cerebrovasculature to physical training-induced brain-derived neurotrophic factor (BDNF) levels elevation in the brain. Brain-derived neurotrophic factor protein levels were measured in the motor cortex 24 h after the last session of a forced treadmill walking (30 minutes a day, 18 m/minute for 7 consecutive days). Unilateral common carotid artery occlusion and modulation of exercise intensity (0 versus -10% inclination of the treadmill) were used as strategies to reduce the (normal) elevation of flow in the cerebrovasculature occurring during exercise. Administration of N-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg before each exercise sessions) and genetic hypertension (spontaneously hypertensive rats) were used as approaches to reduce stimulation of nitric oxide production in response to shear stress elevation. Vascular occlusion totally and partially abolished the effect of physical training on BDNF levels in the hemisphere ipsilateral and contralateral to occlusion, respectively. BDNF levels were higher after high than low exercise intensity. In addition, both genetic hypertension and L-NAME treatment blunted the effects of physical training on BDNF. From these results, we propose that elevation of brain BDNF levels elicited by physical training involves changes in cerebral hemodynamics. PMID:25052557

  12. Comparison of high-intensity vs. high-volume resistance training on the BDNF response to exercise.

    Science.gov (United States)

    Church, David D; Hoffman, Jay R; Mangine, Gerald T; Jajtner, Adam R; Townsend, Jeremy R; Beyer, Kyle S; Wang, Ran; La Monica, Michael B; Fukuda, David H; Stout, Jeffrey R

    2016-07-01

    This study compared the acute and chronic response of circulating plasma brain-derived neurotrophic factor (BDNF) to high-intensity low-volume (HI) and low-intensity high volume (HV) resistance training. Twenty experienced resistance-trained men (23.5 ± 2.6 y, 1.79 ± 0.05 m, 75.7 ± 13.8 kg) volunteered for this study. Before the resistance training program (PRE), participants performed an acute bout of exercise using either the HI [3-5 reps; 90% of one repetition maximum (1RM)] or HV (10-12 reps; 70% 1RM) training paradigm. The acute exercise protocol was repeated after 7 wk of training (POST). Blood samples were obtained at rest (BL), immediately (IP), 30 min (30P), and 60 min (60P) post exercise at PRE and POST. A three-way repeated measure ANOVA was used to analyze acute changes in BDNF concentrations during HI and HV resistance exercise and the effect of 7 wk of training. No training × time × group interaction in BDNF was noted (P = 0.994). Significant main effects for training (P = 0.050) and time (P effect were noted in the BDNF area under the curve response. Results indicate that BDNF concentrations are increased after an acute bout of resistance exercise, regardless of training paradigm, and are further increased during a 7-wk training program in experienced lifters. PMID:27231312

  13. Increased Olfactory Bulb BDNF Expression Does Not Rescue Deficits in Olfactory Neurogenesis in the Huntington's Disease R6/2 Mouse.

    Science.gov (United States)

    Smail, Shamayra; Bahga, Dalbir; McDole, Brittnee; Guthrie, Kathleen

    2016-03-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder caused by expansion of CAG trinucleotide repeats in the huntingtin gene. Mutant huntingtin protein (mhtt) interferes with the actions of brain-derived neurotrophic factor (BDNF), and BDNF signaling is reduced in the diseased striatum. Loss of this trophic support is thought to contribute to loss of striatal medium spiny neurons in HD. Increasing BDNF in the adult striatum or ventricular ependyma slows disease progression in HD mouse models, and diverts subventricular zone (SVZ)-derived neuroblasts from their normal destination, the olfactory bulb, to the striatum, where some survive and develop features of mature neurons. Most neuroblasts that migrate to the olfactory bulb differentiate as granule cells, with approximately half surviving whereas others undergo apoptosis. In the R6/2 HD mouse model, survival of adult-born granule cells is reduced. Newly maturing cells express the BDNF receptor TrkB, suggesting that mhtt may interfere with normal BDNF trophic activity, increasing their loss. To determine if augmenting BDNF counteracts this, we examined granule cell survival in R6/2 mice that overexpress BDNF in olfactory bulb. Although we detected a decline in apoptosis, increased BDNF was not sufficient to normalize granule cell survival within their normal target in R6/2 mice. PMID:26783111

  14. Aging and depression vulnerability interaction results in decreased serotonin innervation associated with reduced BDNF levels in hippocampus of rats bred for learned helplessness

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders B; Santini, Martin A;

    2010-01-01

    density. Hippocampal BDNF protein levels were measured by ELISA. An exacerbated age-related loss of serotonin fiber density specific for the CA1 area was observed in the cLH animals, whereas reduced hippocampal BDNF levels were seen in young and old cLH when compared with age-matched cNLH controls...

  15. Potentiation of Methylmercury-Induced Death in Rat Cerebellar Granular Neurons Occurs by Further Decrease of Total Intracellular GSH with BDNF via TrkB in Vitro.

    Science.gov (United States)

    Sakaue, Motoharu; Maki, Takehiro; Kaneko, Takuya; Hemmi, Natsuko; Sekiguchi, Hitomi; Horio, Tomoyo; Kadowaki, Erina; Ozawa, Aisa; Yamamoto, Masako

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is a principal factor for neurogenesis, neurodevelopment and neural survival through a BDNF receptor, tropomyosin-related kinase (Trk) B, while BDNF can also cause a decrease in the intracellular glutathione (GSH) level. We investigated the exacerbation of methylmercury-induced death of rat cerebellar granular neurons (CGNs) by BDNF in vitro. Since methylmercury can decrease intracellular GSH levels, we hypothesized that a further decrease of the intracellular GSH level is involved in the process of the exacerbation of neuronal cell death. In the present study, we established that in CGN culture, a decrease of the intracellular GSH level was further potentiated with BDNF in the process of the methylmercury-induced neuronal death and also in GSH reducer-induced neuronal death. BDNF treatment promoted the decrease in GSH levels induced by methylmercury and also by L-buthionine sulfoximine (BSO) and diethyl maleate (DEM). The promoting effect of BDNF was observed in a TrkB-vector transformant of the rat neuroblastoma B35 cell line but not in the mock-vector transformant. These results indicate that the exacerbating effect of BDNF on methylmercury-induced neuronal death in cultures of CGNs includes a further decrease of intracellular GSH levels, for which TrkB is essential. PMID:27251509

  16. Association of COMT (Val158Met) and BDNF (Val66Met) Gene Polymorphisms with Anxiety, ADHD and Tics in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Gadow, Kenneth D.; Roohi, Jasmin; Devincent, Carla J.; Kirsch, Sarah; Hatchwell, Eli

    2009-01-01

    The aim of the study is to examine rs4680 ("COMT") and rs6265 ("BDNF") as genetic markers of anxiety, ADHD, and tics. Parents and teachers completed a DSM-IV-referenced rating scale for a total sample of 67 children with autism spectrum disorder (ASD). Both "COMT" (p = 0.06) and "BDNF" (p = 0.07) genotypes were marginally significant for teacher…

  17. Defects of organization in rendering medical aid

    Directory of Open Access Journals (Sweden)

    Shavkat Islamov

    2010-09-01

    Full Text Available The defects of organization at the medical institution mean disturbance of rules, norms and order of rendering of medical aid. The number of organization defects in Uzbekistan increased from 20.42%, in 1999 to 25.46% in 2001 with gradual decrease to 19.9% in 2003 and 16.66%, in 2006 and gradual increase to 21.95% and 28.28% (P<0.05 in 2005 and 2008. Among the groups of essential defects of organization there were following: disturbance of transportation rules, lack of dispensary care, shortcomings in keeping medical documentation.

  18. Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A2A receptor-dependent manner: A2A receptor blockade prevents BDNF release and proliferation of microglia

    OpenAIRE

    Gomes Catarina; Ferreira Raquel; George Jimmy; Sanches Rui; Rodrigues Diana I; Gonçalves Nélio; Cunha Rodrigo A

    2013-01-01

    Abstract Background Brain-derived neurotrophic factor (BDNF) has been shown to control microglial responses in neuropathic pain. Since adenosine A2A receptors (A2ARs) control neuroinflammation, as well as the production and function of BDNF, we tested to see if A2AR controls the microglia-dependent secretion of BDNF and the proliferation of microglial cells, a crucial event in neuroinflammation. Methods Murine N9 microglial cells were challenged with lipopolysaccharide (LPS, 100 ng/mL) in the...

  19. Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

    Science.gov (United States)

    Martínez-Levy, G A; Rocha, L; Lubin, F D; Alonso-Vanegas, M A; Nani, A; Buentello-García, R M; Pérez-Molina, R; Briones-Velasco, M; Recillas-Targa, F; Pérez-Molina, A; San-Juan, D; Cienfuegos, J; Cruz-Fuentes, C S

    2016-02-01

    A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (pTPM) (N=3) was associated to a decrease in BDNFVI expression (pTPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs. PMID:26621122

  20. BDNF Val66met and 5-HTTLPR polymorphisms predict a human in vivo marker for brain serotonin levels

    DEFF Research Database (Denmark)

    Fisher, Patrick M; Holst, Klaus K; Adamsen, Dea; Klein, Anders Bue; Frokjaer, Vibe G; Jensen, Peter S; Svarer, Claus; Gillings, Nic; Baare, William F C; Mikkelsen, Jens D; Knudsen, Gitte M

    2015-01-01

    BDNF val66met significantly predicted a LV reflecting [(11) C]SB207145 binding across regions (P = 0.005). BDNF val66met met-carriers showed 2-9% higher binding relative to val/val homozygotes. In contrast, 5-HTTLPR did not predict the LV but S-carriers showed 7% lower neocortical binding relative to...... LL homozygotes (P = 7.3 × 10(-6) ). We observed no evidence for genetic interaction. Our findings indicate that BDNF val66met significantly predicts a common regulator of brain [(11) C]SB207145 binding, which we hypothesize reflects brain serotonin levels. In contrast, our data indicate that 5-HTTLPR...

  1. A pilot study on the effect of cognitive training on BDNF serum levels in individuals with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Francesco Angelucci

    2015-03-01

    Thus, in this pilot study we evaluated the effect of a cognitive rehabilitation protocol focused on the training of executive functioning and measured BDNF serum levels in a group of PD patients with mild cognitive impairment, as compared to the effect of a placebo treatment (n=7/8 group. The results showed that PD patients undergoing the cognitive rehabilitation, besides improving their cognitive performance as measured with the Zoo Map test, also displayed increased serum BDNF levels as compared to the placebo group. These findings suggest that BDNF serum levels may represent a biomarker of the effects of cognitive rehabilitation in PD patients affected by MCI. However, the functional significance of this increase in PD as well as other neuropathological conditions remains to be determined.

  2. 49 CFR 215.9 - Movement of defective cars for repair.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of defective cars for repair. 215.9... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS General § 215.9 Movement of defective cars for repair. (a) A railroad freight car which has any component described as defective in...

  3. Noopept stimulates the expression of NGF and BDNF in rat hippocampus.

    Science.gov (United States)

    Ostrovskaya, R U; Gudasheva, T A; Zaplina, A P; Vahitova, Ju V; Salimgareeva, M H; Jamidanov, R S; Seredenin, S B

    2008-09-01

    We studied the effect of original dipeptide preparation Noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) with nootropic and neuroprotective properties on the expression of mRNA for neurotropic factors NGF and BDNF in rat hippocampus. Expression of NGF and BDNF mRNA in the cerebral cortex and hippocampus was studied by Northern blot analysis. Taking into account the fact that pharmacological activity of Noopept is realized after both acute and chronic treatment, we studied the effect of single and long-term treatment (28 days) with this drug. Expression of the studied neurotropic factors in the cerebral cortex was below the control after single administration of Noopept, while chronic administration caused a slight increase in BDNF expression. In the hippocampus, expression of mRNA for both neurotrophins increased after acute administration of Noopept. Chronic treatment with Noopept was not followed by the development of tolerance, but even potentiated the neurotrophic effect. These changes probably play a role in neuronal restoration. We showed that the nootropic drug increases expression of neurotrophic factors in the hippocampus. Our results are consistent with the hypothesis that neurotrophin synthesis in the hippocampus determines cognitive function, particularly in consolidation and delayed memory retrieval. Published data show that neurotrophic factor deficiency in the hippocampus is observed not only in advanced Alzheimer's disease, but also at the stage of mild cognitive impairment (pre-disease state). In light of this our findings suggest that Noopept holds much promise to prevent the development of Alzheimer's disease in patients with mild cognitive impairment. Moreover, therapeutic effectiveness of Noopept should be evaluated at the initial stage of Alzheimer's disease. PMID:19240853

  4. Hydroxysafflor yellow A increases BDNF and NMDARs in the hippocampus in a vascular dementia rat model.

    Science.gov (United States)

    Xing, Mengya; Sun, Qingna; Wang, Yiyi; Cheng, Yan; Zhang, Nan

    2016-07-01

    Hydroxysafflor yellow A (HSYA) is a drug that exerts angiogenesis regulatory and neuroprotective effects and has become an effective therapy for brain and heart ischemic disorders. There is no definite evidence supporting a therapeutic effect of HSYA in vascular dementia (VaD). We used HSYA in a rat model of chronic cerebral ischemia to determine its potential therapeutic effects in VaD. The Morris water maze (MWM) was used to evaluate spatial cognitive function, and long-term potentiation (LTP) was tested as a marker of synaptic plasticity. The expression levels of brain-derived neurotrophic factor (BDNF) and two subunits of N-methyl-d-aspartate receptor (NMDAR; GluN2A and GluN2B) in the hippocampus were measured via western blotting. The MWM results showed that the experimental VaD group had longer escape latencies than the sham group, whereas the HSYA group had a decreased escape latency compared with the VaD group (P<0.05). The LTP at CA3-CA1 synapses in the hippocampus was also enhanced in the HSYA compared with the VaD group (P<0.05). The western blotting results revealed lower hippocampal BDNF and GluN2B expression in the VaD group compared with the sham group and significantly higher hippocampal expression in the HSYA group compared with the VaD group. No significant change in GluN2A expression was detected. The results indicate that HSYA may enhance the endogenous expression of BDNF and GluN2B, which are associated with the synaptic plasticity of the hippocampus, and may improve spatial learning and memory abilities in a rat model of VaD. PMID:27086971

  5. Metabotropic glutamate receptor 2 and corticotrophin-releasing factor receptor-1 gene expression is differently regulated by BDNF in rat primary cortical neurons

    DEFF Research Database (Denmark)

    Jørgensen, Christinna V; Klein, Anders B; El-Sayed, Mona;

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and plasticity. Incorporation of matured receptor proteins is an integral part of synapse formation. However, whether BDNF increases synthesis and integration of receptors in functional synapses directly is unclear. We are...... after neuronal depolarization produced by high potassium. This study emphasizes the role of BDNF as an important regulator of receptor compositions in the synapse and provides further evidence that BDNF directly regulates important drug targets involved in cognition and mood. Synapse 67:794-800, 2013...... expression for all these receptors, as well as a number of immediate-early genes, was pharmacologically characterized in primary neurons from rat frontal cortex. BDNF increased CRF-R1 mRNA levels up to fivefold, whereas mGluR2 mRNA levels were proportionally downregulated. No effect on 5-HT2A R mRNA was seen...

  6. Defect chemistry and defect engineering of TiO2-based semiconductors for solar energy conversion.

    Science.gov (United States)

    Nowotny, Janusz; Alim, Mohammad Abdul; Bak, Tadeusz; Idris, Mohammad Asri; Ionescu, Mihail; Prince, Kathryn; Sahdan, Mohd Zainizan; Sopian, Kamaruzzaman; Mat Teridi, Mohd Asri; Sigmund, Wolfgang

    2015-12-01

    This tutorial review considers defect chemistry of TiO2 and its solid solutions as well as defect-related properties associated with solar-to-chemical energy conversion, such as Fermi level, bandgap, charge transport and surface active sites. Defect disorder is discussed in terms of defect reactions and the related charge compensation. Defect equilibria are used in derivation of defect diagrams showing the effect of oxygen activity and temperature on the concentration of both ionic and electronic defects. These defect diagrams may be used for imposition of desired semiconducting properties that are needed to maximize the performance of TiO2-based photoelectrodes for the generation of solar hydrogen fuel using photo electrochemical cells (PECs) and photocatalysts for water purification. The performance of the TiO2-based semiconductors is considered in terms of the key performance-related properties (KPPs) that are defect related. It is shown that defect engineering may be applied for optimization of the KPPs in order to achieve optimum performance. PMID:26446476

  7. Stage-dependent association of BDNF and TGF-β1 with lung function in stable COPD

    Directory of Open Access Journals (Sweden)

    Stoll Paul

    2012-12-01

    Full Text Available Abstract Background Chronic Obstructive Pulmonary Disease (COPD is characterised by complex inflammatory, neuronal and fibrotic changes. Brain-derived Neurotrophic Factor (BDNF is a key regulator of neuronal plasticity, whereas Transforming Growth Factor-β1 (TGF-β1 plays a crucial role in tissue repair and emphysema pathogenesis. Both mediators are stored in platelets and released from platelets in inflammatory conditions and during serum preparation. In patients with asthma, it was previously shown that elevated serum BDNF concentrations correlate with disease severity, whereas TGF-β1 concentrations were normal. Methods In the present study, 63 patients with stable COPD (spirometric GOLD stages 2–4 and 17 age- and comorbidity-matched controls were studied. Lung function, smoking history, medication, platelet concentrations in peripheral blood and serum concentrations of BDNF, TGF-β1 and Serotonin (5-HT were assessed in all participants. Results Serum levels of both BDNF and TGF-β1 (but not concentrations of platelets in peripheral blood were significantly elevated in all stages of COPD as compared to controls. Highest BDNF concentrations were found in spirometric GOLD stage 3, whereas highest TGF-β1 serum levels were found in spirometric GOLD stage 4. There were specific, stage-dependent correlations of these mediators with lung function parameters of the patients. Conclusions Taken together, we show that, in contrast to asthma, COPD is characterised by elevated concentrations of both BDNF and TGF-β1 in serum. The stage-dependent association with lung function supports the hypothesis that these platelet mediators may play a role in the pathogenesis of COPD.

  8. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy

    DEFF Research Database (Denmark)

    Klein, Anders B; Jennum, Poul; Knudsen, Stine;

    2013-01-01

    Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction in...... hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesised that...

  9. Facts about Birth Defects

    Science.gov (United States)

    ... Us Information For... Media Policy Makers Facts about Birth Defects Language: English Español (Spanish) Recommend on Facebook Tweet ... having a baby born without a birth defect. Birth Defects Are Common Every 4 ½ minutes, a baby ...

  10. BDNF up-regulates evoked GABAergic transmission in developing hippocampus by potentiating presynaptic N- and P/Q-type Ca2+ channels signalling.

    Science.gov (United States)

    Baldelli, P; Novara, M; Carabelli, V; Hernández-Guijo, J M; Carbone, E

    2002-12-01

    Chronic application of brain-derived neurotrophic factor (BDNF) induces new selective synthesis of non-L-type Ca2+ channels (N, P/Q, R) at the soma of cultured hippocampal neurons. As N- and P/Q-channels support neurotransmitter release in the hippocampus, this suggests that BDNF-treatment may enhance synaptic transmission by increasing the expression of presynaptic Ca2+ channels as well. To address this issue we studied the long-term effects of BDNF on miniature and stimulus-evoked GABAergic transmission in rat embryo hippocampal neurons. We found that BDNF increased the frequency of miniature currents (mIPSCs) by approximately 40%, with little effects on their amplitude. BDNF nearly doubled the size of evoked postsynaptic currents (eIPSCs) with a marked increase of paired-pulse depression, which is indicative of a major increase in presynaptic activity. The potentiation of eIPSCs was more relevant during the first two weeks in culture, when GABAergic transmission is depolarizing. BDNF action was mediated by TrkB-receptors and had no effects on: (i) the amplitude and dose-response of GABA-evoked IPSCs and (ii) the number of GABA(A) receptor clusters and the total functioning synapses, suggesting that the neurotrophin unlikely acted postsynaptically. In line with this, BDNF affected the contribution of voltage-gated Ca2+ channels mediating evoked GABAergic transmission. BDNF drastically increased the fraction of evoked IPSCs supported by N- and P/Q-channels while it decreased the contribution associated with R- and L-types. This selective action resembles the previously observed up-regulatory effects of BDNF on somatic Ca2+ currents in developing hippocampus, suggesting that potentiation of presynaptic N- and P/Q-channel signalling belongs to a manifold mechanism by which BDNF increases the efficiency of stimulus-evoked GABAergic transmission. PMID:12492424

  11. [Anxiety and polymorphism Val66Met of BDNF gene--predictors of depression severity in ischemic heart disease].

    Science.gov (United States)

    Golimbet, V E; Volel', B A; Kopylov, F Iu; Dolzhikov, A V; Korovaitseva, G I; Kasparov, S V; Isaeva, M I

    2015-01-01

    In a framework of search for early predictors of depression in patients with ischemic heart disease (IHD) we studied effect of molecular-genetic factors (polymorphism of brain-derived neirotrophic factor--BDNF), personality traits (anxiety, neuroticism), IHD severity, and psychosocial stressors on manifestations of depression in men with verified diagnosis of IHD. Severity of depression was assessed by Hamilton Depression Rating Scale 21-item (HAMD 21), anxiety and neuroticism were evaluated by the Spielberger State-Trait Anxiety Inventory and "Big Five" questionnaire, respectively. It wa shown that personal anxiety and ValVal genotype of BDNF gene appeared to be predictors of moderate and severe depression. PMID:26050483

  12. Differential brain and spinal cord cytokine and BDNF levels in experimental autoimmune encephalomyelitis are modulated by prior and regular exercise.

    Science.gov (United States)

    Bernardes, Danielle; Oliveira-Lima, Onésia Cristina; Silva, Thiago Vitarelli da; Faraco, Camila Cristina Fraga; Leite, Hércules Ribeiro; Juliano, Maria Aparecida; Santos, Daniel Moreira dos; Bethea, John R; Brambilla, Roberta; Orian, Jacqueline M; Arantes, Rosa Maria Esteves; Carvalho-Tavares, Juliana

    2013-11-15

    The interactions between a prior program of regular exercise and the development of experimental autoimmune encephalomyelitis (EAE)-mediated responses were evaluated. In the exercised EAE mice, although there was no effect on infiltrated cells, the cytokine and derived neurotrophic factor (BDNF) levels were altered, and the clinical score was attenuated. Although, the cytokine levels were decreased in the brain and increased in the spinal cord, BDNF was elevated in both compartments with a tendency of lesser demyelization volume in the spinal cord of the exercised EAE group compared with the unexercised. PMID:24054000

  13. Defect production in ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J. [Oak Ridge National Lab., TN (United States); Kinoshita, C. [Kyushu Univ. (Japan)

    1997-08-01

    A review is given of several important defect production and accumulation parameters for irradiated ceramics. Materials covered in this review include alumina, magnesia, spinel silicon carbide, silicon nitride, aluminum nitride and diamond. Whereas threshold displacement energies for many ceramics are known within a reasonable level of uncertainty (with notable exceptions being AIN and Si{sub 3}N{sub 4}), relatively little information exists on the equally important parameters of surviving defect fraction (defect production efficiency) and point defect migration energies for most ceramics. Very little fundamental displacement damage information is available for nitride ceramics. The role of subthreshold irradiation on defect migration and microstructural evolution is also briefly discussed.

  14. Defect production in ceramics

    International Nuclear Information System (INIS)

    A review is given of several important defect production and accumulation parameters for irradiated ceramics. Materials covered in this review include alumina, magnesia, spinel silicon carbide, silicon nitride, aluminum nitride and diamond. Whereas threshold displacement energies for many ceramics are known within a reasonable level of uncertainty (with notable exceptions being AIN and Si3N4), relatively little information exists on the equally important parameters of surviving defect fraction (defect production efficiency) and point defect migration energies for most ceramics. Very little fundamental displacement damage information is available for nitride ceramics. The role of subthreshold irradiation on defect migration and microstructural evolution is also briefly discussed

  15. Defect production in ceramics

    International Nuclear Information System (INIS)

    A review is given of several important defect production and accumulation parameters for irradiated ceramics. Materials covered in this review include alumina, magnesia, spinel, silicon carbide, silicon nitride, aluminum nitride and diamond. Whereas threshold displacement energies for many ceramics are known within a reasonable level of uncertainty (with notable exceptions being AlN and Si3N4), relatively little information exists on the equally important parameters of surviving defect fraction (defect production efficiency) and point defect migration energies for most ceramics. Very little fundamental displacement damage information is available for nitride ceramics. The role of subthreshold irradiation on defect migration and microstructural evolution is also briefly discussed. (orig.)

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

    Directory of Open Access Journals (Sweden)

    HarishBabu

    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.

  17. Association Study between BDNF Gene Polymorphisms and Autism by Three-Dimensional Gel-Based Microarray

    Directory of Open Access Journals (Sweden)

    Zuhong Lu

    2009-06-01

    Full Text Available Single nucleotide polymorphisms (SNPs are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (χ2 = 7.809, p = 0.005 and genotype (χ2 = 7.800, p = 0.020. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (χ2 = 28.19,p = 3.44e-005. We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high-throughput method for SNPs genotyping, and can be used for association study of susceptible gene with disorders in large samples.

  18. Nature vs. nurture: can enrichment rescue the behavioural phenotype of BDNF heterozygous mice?

    Science.gov (United States)

    Chourbaji, Sabine; Brandwein, Christiane; Vogt, Miriam A; Dormann, Christof; Hellweg, Rainer; Gass, Peter

    2008-10-10

    In earlier experiments we have demonstrated that group-housing in a rather impoverished "standard" environment can be a crucial stress factor in male C57Bl/6 mice. The present study aimed at investigating the effect of combining a probable genetic vulnerability--postulated by the "Neurotrophin Hypothesis of Depression"--with the potentially modulating influence of a stressful environment such as "impoverished" standard housing conditions. For that purpose mice with a partial deletion of brain-derived neurotrophic factor (BDNF) were group-housed under standard and enriched housing conditions and analysed in a well-established test battery for emotional behaviours. Standard group-housing affected emotional behaviour in male and female BDNF heterozygous mice, causing an increase in anxiety, changes in exploration as well as nociception. Providing the animals' cages with supplementary enrichment, however, led to a rescue of emotional alterations, which emphasises the significance of external factors and their relevance for a valid investigation of genetic aspects in these mutants as well as others, which may be examined in terms of stress-responsiveness or emotionality. PMID:18538870

  19. CREB-BDNF Pathway Influences Alcohol Cue-Elicited Hyperactivation in Drinkers

    Science.gov (United States)

    Chen, Jiayu; Hutchison, Kent E.; Calhoun, Vince D.; Claus, Eric; Turner, Jessica A.; Sui, Jing; Liu, Jingyu

    2016-01-01

    Alcohol dependence (AD) is suggested to have polygenic risk factors and also exhibits neurological complications, strongly encouraging a translational study to explore the associations between aggregates of genetic variants and brain function alterations related to alcohol use. In this study, we used a semiblind multivariate approach, parallel independent component analysis with multiple references (pICA-MR) to investigate relationships of genome-wide single nucleotide polymorphisms (SNPs) with alcohol cue elicited brain activations in 326 healthy drinkers. The genetic component derived from the CREB-BDNF pathway reference was significantly associated (r = −0.36, p = 2.98×10−11) with an imaging component reflecting hyperactivation in precuneus, superior parietal lobule, and posterior cingulate for drinkers with more severe AD scores. The highlighted brain regions participate in many cognitive processes and have been robustly implicated in craving-related studies. The genetic factor highlighted the CREB and BDNF references, as well as other genes including GRM5, GRM7, GRID1, GRIN2A, PRKCA and PRKCB. Ingenuity Pathway Analysis indicated that the genetic component was enriched in synaptic plasticity, GABA and protein kinase A signaling. In summary, our findings suggest genetic variations in various neural plasticity and signaling pathways partially explain the variance of precuneus reactivity to alcohol cue which appears to be associated with AD severity. PMID:25939814

  20. Gradually Increased Training Intensity Benefits Rehabilitation Outcome after Stroke by BDNF Upregulation and Stress Suppression

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    Jing Sun

    2014-01-01

    Full Text Available Physical training is necessary for effective rehabilitation in the early poststroke period. Animal studies commonly use fixed training intensity throughout rehabilitation and without adapting it to the animals' recovered motor ability. This study investigated the correlation between training intensity and rehabilitation efficacy by using a focal ischemic stroke rat model. Eighty male Sprague-Dawley rats were induced with middle cerebral artery occlusion/reperfusion surgery. Sixty rats with successful stroke were then randomly assigned into four groups: control (CG, n=15, low intensity (LG, n=15, gradually increased intensity (GIG, n=15, and high intensity (HG, n=15. Behavioral tests were conducted daily to evaluate motor function recovery. Stress level and neural recovery were evaluated via plasma corticosterone and brain-derived neurotrophic factor (BDNF concentration, respectively. GIG rats significantly (P<0.05 recovered motor function and produced higher hippocampal BDNF (112.87 ± 25.18 ng/g. GIG and LG rats exhibited similar stress levels (540.63 ± 117.40 nM/L and 508.07 ± 161.30 nM/L, resp., which were significantly lower (P<0.05 than that (716.90 ± 156.48 nM/L of HG rats. Training with gradually increased intensity achieved better recovery with lower stress. Our observations indicate that a training protocol that includes gradually increasing training intensity should be considered in both animal and clinical studies for better stroke recovery.

  1. Holographic Experiments on Defects

    CERN Document Server

    Wapler, Matthias C

    2009-01-01

    Using the AdS/CFT correspondence, we study the anisotropic charge transport properties of both supersymmetric and non-supersymmetric matter fields on (2+1)-dimensional defects coupled to a (3+1)-dimensional ${\\cal N}=4$ SYM "heat bath". We focus on the case of a finite external background magnetic field, finite net charge density and finite mass. At high frequencies, we discover a spectrum of quasiparticle resonances due to the magnetic field and finite density and at small frequencies, we perform a Drude-like expansion around the DC limit. Both of these regimes display many generic features and some features that we attribute to strong coupling, such as a minimum DC conductivity and an unusual behavior of the "cyclotron" and plasmon frequencies, which become related to the resonances found in the conformal case in an earlier paper. We further study the hydrodynamic regime and the relaxation properties, from which the system displays a set of different possible transitions to the collisionless regime. The mas...

  2. Advances in the research of BDNF with cerebral ischemia%脑源性神经营养因子与脑缺血的研究进展

    Institute of Scientific and Technical Information of China (English)

    付美红; 李海涛

    2012-01-01

    脑源性神经营养因子(brain derived neurotrophic factor,BDNF)是在脑内形成的一类神经营养因子.BDNF通过作用于其特异性受体TrkB、P75促进神经元的生长发育同时修复受损的神经元.BDNF对缺血性脑损伤的保护机制是通过下调钙离子浓度,减小Bax/Bcl-2比值,对抗NO毒性等途径实现的.该文介绍了BDNF的基本作用及其与脑缺血的相关作用研究,综述了BDNF的应用方法研究.%Brain derived neurotrophic factor ( BDNF ) is a class of neurotrophic factor formed within the brain. BDNF promotes the growth and development of the neurons and repair the damaged neurons acting on its specific receptors TrkB and P75. BDNF plays a key role in ischemic damage protection mainly by eliminating oxygen-derived free radicals, reducing Bax/Bcl-2 ratio, regulating the low levels of ca2 + and against NO toxicity as well. This paper introduces the basic function of BDNF and the related research of BDNF on ischemic damage. The article reviews the research of the application methods of BDNF.

  3. Music exposure improves spatial cognition by enhancing the BDNF level of dorsal hippocampal subregions in the developing rats.

    Science.gov (United States)

    Xing, Yingshou; Chen, Wenxi; Wang, Yanran; Jing, Wei; Gao, Shan; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-03-01

    Previous research has shown that dorsal hippocampus plays an important role in spatial memory process. Music exposure can enhance brain-derived neurotrophic factor (BDNF) expression level in dorsal hippocampus (DH) and thus enhance spatial cognition ability. But whether music experience may affect different subregions of DH in the same degree remains unclear. Here, we studied the effects of exposure to Mozart K.448 on learning behavior in developing rats using the classical Morris water maze task. The results showed that early music exposure could enhance significantly learning performance of the rats in the water maze test. Meanwhile, the BDNF/TrkB level of dorsal hippocampus CA3 (dCA3) and dentate gyrus (dDG) was significantly enhanced in rats exposed to Mozart music as compared to those without music exposure. In contrast, the BDNF/TrkB level of dorsal hippocampus CA1 (dCA1) was not affected. The results suggest that the spatial memory improvement by music exposure in rats may be associated with the enhanced BDNF/TrkB level of dCA3 and dDG. PMID:26802511

  4. Activation of the cAMP Pathway Induces RACK1-Dependent Binding of β-Actin to BDNF Promoter

    Science.gov (United States)

    Neasta, Jeremie; Fiorenza, Anna; He, Dao-Yao; Phamluong, Khanhky; Kiely, Patrick A.; Ron, Dorit

    2016-01-01

    RACK1 is a scaffolding protein that contributes to the specificity and propagation of several signaling cascades including the cAMP pathway. As such, RACK1 participates in numerous cellular functions ranging from cell migration and morphology to gene transcription. To obtain further insights on the mechanisms whereby RACK1 regulates cAMP-dependent processes, we set out to identify new binding partners of RACK1 during activation of the cAMP signaling using a proteomics strategy. We identified β-actin as a direct RACK1 binding partner and found that the association between β-actin and RACK1 is increased in response to the activation of the cAMP pathway. Furthermore, we show that cAMP-dependent increase in BDNF expression requires filamentous actin. We further report that β-actin associates with the BDNF promoter IV upon the activation of the cAMP pathway and present data to suggest that the association of β-actin with BDNF promoter IV is RACK1-dependent. Taken together, our data suggest that β-actin is a new RACK1 binding partner and that the RACK1 and β-actin association participate in the cAMP-dependent regulation of BDNF transcription. PMID:27505161

  5. The BDNF Val66Met polymorphism is associated with the functional connectivity dynamics of pain modulatory systems in primary dysmenorrhea.

    Science.gov (United States)

    Wei, Shyh-Yuh; Chao, Hsiang-Tai; Tu, Cheng-Hao; Lin, Ming-Wei; Li, Wei-Chi; Low, Intan; Shen, Horng-Der; Chen, Li-Fen; Hsieh, Jen-Chuen

    2016-01-01

    Primary dysmenorrhea (PDM), menstrual pain without an organic cause, is a prevailing problem in women of reproductive age. We previously reported alterations of structure and functional connectivity (FC) in the periaqueductal gray (PAG) of PDM subjects. Given that the brain derived neurotrophic factor (BDNF) acts as a pain modulator within the PAG and the BDNF Val66Met polymorphism contributes towards susceptibility to PDM, the present study of imaging genetics set out to investigate the influence of, firstly, the BDNF Val66Met single nucleotide polymorphism and, secondly, the genotype-pain interplays on the descending pain modulatory systems in the context of PAG-seeded FC patterning. Fifty-six subjects with PDM and 60 controls participated in the current study of resting-state functional magnetic resonance imaging (fMRI) during the menstruation and peri-ovulatory phases; in parallel, blood samples were taken for genotyping. Our findings indicate that the BDNF Val66Met polymorphism is associated with the diverse functional expressions of the descending pain modulatory systems. Furthermore, PAG FC patterns in pain-free controls are altered in women with PDM in a genotype-specific manner. Such resilient brain dynamics may underpin the individual differences and shed light on the vulnerability for chronic pain disorders of PDM subjects. PMID:27010666

  6. The BDNF gene Val66Met polymorphism as a modifier of psychiatric disorder susceptibility: progress and controversy.

    Science.gov (United States)

    Notaras, M; Hill, R; van den Buuse, M

    2015-08-01

    Brain-derived neurotrophic factor (BDNF) has a primary role in neuronal development, differentiation and plasticity in both the developing and adult brain. A single-nucleotide polymorphism in the proregion of BDNF, termed the Val66Met polymorphism, results in deficient subcellular translocation and activity-dependent secretion of BDNF, and has been associated with impaired neurocognitive function in healthy adults and in the incidence and clinical features of several psychiatric disorders. Research investigating the Val66Met polymorphism has increased markedly in the past decade, and a gap in integration exists between and within academic subfields interested in the effects of this variant. Here we comprehensively review the role and relevance of the Val66Met polymorphism in psychiatric disorders, with emphasis on suicidal behavior and anxiety, eating, mood and psychotic disorders. The cognitive and molecular neuroscience of the Val66Met polymorphism is also concisely reviewed to illustrate the effects of this genetic variant in healthy controls, and is complemented by a commentary on the behavioral neuroscience of BDNF and the Val66Met polymorphism where relevant to specific disorders. Lastly, a number of controversies and unresolved issues, including small effect sizes, sampling of allele inheritance but not genotype and putative ethnicity-specific effects of the Val66Met polymorphism, are also discussed to direct future research. PMID:25824305

  7. Spirulina non-protein components induce BDNF gene transcription via HO-1 activity in C6 glioma cells.

    Science.gov (United States)

    Morita, Kyoji; Itoh, Mari; Nishibori, Naoyoshi; Her, Song; Lee, Mi-Sook

    2015-01-01

    Blue-green algae are known to contain biologically active proteins and non-protein substances and considered as useful materials for manufacturing the nutritional supplements. Particularly, Spirulina has been reported to contain a variety of antioxidants, such as flavonoids, carotenoids, and vitamin C, thereby exerting their protective effects against the oxidative damage to the cells. In addition to their antioxidant actions, polyphenolic compounds have been speculated to cause the protection of neuronal cells and the recovery of neurologic function in the brain through the production of brain-derived neurotrophic factor (BDNF) in glial cells. Then, the protein-deprived extract was prepared by removing the most part of protein components from aqueous extract of Spirulina platensis, and the effect of this extract on BDNF gene transcription was examined in C6 glioma cells. Consequently, the protein-deprived extract was shown to cause the elevation of BDNF mRNA levels following the expression of heme oxygenase-1 (HO-1) in the glioma cells. Therefore, the non-protein components of S. platensis are considered to stimulate BDNF gene transcription through the HO-1 induction in glial cells, thus proposing a potential ability of the algae to indirectly modulate the brain function through the glial cell activity. PMID:25349086

  8. CART attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion.

    Science.gov (United States)

    Qiu, Bin; Hu, Shengdi; Liu, Libing; Chen, Man; Wang, Lai; Zeng, Xianwei; Zhu, Shigong

    2013-07-12

    Cocaine and amphetamine regulated transcript (CART), a neuropeptide, has shown strong neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury in vivo and in vitro. Here, we report a new effect of CART on ER stress which is induced by cerebral I/R in a rat model of middle cerebral artery occlusion (MCAO) or by oxygen and glucose deprivation (OGD) in cultured cortical neurons, as well as a new functionality of BDNF in the neuroprotection by CART against the ER stress in cerebral I/R. The results showed that CART was effective in reducing the neuronal apoptosis and expression of ER stress markers (GRP78, CHOP and cleaved caspase12), and increasing the BDNF expression in I/R injury rat cortex both in vivo and in vitro. In addition, the effects of CART on ischemia-induced neuronal apoptosis and ER stress were suppressed by tyrosine receptor kinase B (TrkB) IgG, whereas the effects of CART on BDNF transcription, synthesis and secretion were abolished by CREB siRNA. This work suggests that CART is functional in inhibiting the cerebral I/R-induced ER stress and neuronal apoptosis by facilitating the transcription, synthesis and secretion of BDNF in a CREB-dependent way. PMID:23770418

  9. Predicting Response Trajectories during Cognitive-Behavioural Therapy for Panic Disorder: No Association with the BDNF Gene or Childhood Maltreatment.

    Directory of Open Access Journals (Sweden)

    Martí Santacana

    Full Text Available Anxiety disorders are highly prevalent and result in low quality of life and a high social and economic cost. The efficacy of cognitive-behavioural therapy (CBT for anxiety disorders is well established, but a substantial proportion of patients do not respond to this treatment. Understanding which genetic and environmental factors are responsible for this differential response to treatment is a key step towards "personalized medicine". Based on previous research, our objective was to test whether the BDNF Val66Met polymorphism and/or childhood maltreatment are associated with response trajectories during exposure-based CBT for panic disorder (PD.We used Growth Mixture Modeling to identify latent classes of change (response trajectories in patients with PD (N = 97 who underwent group manualized exposure-based CBT. We conducted logistic regression to investigate the effect on these trajectories of the BDNF Val66Met polymorphism and two different types of childhood maltreatment, abuse and neglect.We identified two response trajectories ("high response" and "low response", and found that they were not significantly associated with either the genetic (BDNF Val66Met polymorphism or childhood trauma-related variables of interest, nor with an interaction between these variables.We found no evidence to support an effect of the BDNF gene or childhood trauma-related variables on CBT outcome in PD. Future studies in this field may benefit from looking at other genotypes or using different (e.g. whole-genome approaches.

  10. Exposure to sub-chronic unpredictable stress accounts for antidepressant-like effects in hamsters treated with BDNF and CNQX.

    Science.gov (United States)

    Alò, Raffaella; Mele, Maria; Fazzari, Gilda; Avolio, Ennio; Canonaco, Marcello

    2015-09-01

    Recent evidences indicate that cerebral neurotrophic factors like vascular endothelial growth factor plus signaling pathways of the glutamatergic neuroreceptor system (L-Glu) are determinant modulators of depression-like states. In the present study, the type of interaction(s) exerted by the AMPAergic antagonist, 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) and the brain derived neurotrophic factor (BDNF) on depression-like behaviors in hamsters (Mesocricetus auratus) were investigated. Sub-chronic administration of BDNF in the hippocampal dentate gyrus (DG) of stressed hamsters was responsible for very evident (pdepression states, were reduced following treatment with both compounds. Contextually, marked mRNA expression levels of the BDNF receptor (tropomyosin-related kinase B; TrkB) were detected in DG and the oriens-pyramidalis of HIP (Or-Py) while a moderate (pcaused moderate increases of the major stress protein (Hsp70) in DG and Or-Py. Conversely, while CNQX induced similar TrkB expression levels, it instead accounted for a moderate reduction of Hsp70 mRNAs in the same brain areas. Overall these results support crucial roles played by BDNF and AMPAergic neurosignaling mechanisms during distinct adaptive responses of depression- and anxiety-like states in hamsters. PMID:26409118

  11. Predicting Response Trajectories during Cognitive-Behavioural Therapy for Panic Disorder: No Association with the BDNF Gene or Childhood Maltreatment

    Science.gov (United States)

    Santacana, Martí; Arias, Bárbara; Mitjans, Marina; Bonillo, Albert; Montoro, María; Rosado, Sílvia; Guillamat, Roser; Vallès, Vicenç; Pérez, Víctor; Forero, Carlos G.; Fullana, Miquel A.

    2016-01-01

    Background Anxiety disorders are highly prevalent and result in low quality of life and a high social and economic cost. The efficacy of cognitive-behavioural therapy (CBT) for anxiety disorders is well established, but a substantial proportion of patients do not respond to this treatment. Understanding which genetic and environmental factors are responsible for this differential response to treatment is a key step towards “personalized medicine”. Based on previous research, our objective was to test whether the BDNF Val66Met polymorphism and/or childhood maltreatment are associated with response trajectories during exposure-based CBT for panic disorder (PD). Method We used Growth Mixture Modeling to identify latent classes of change (response trajectories) in patients with PD (N = 97) who underwent group manualized exposure-based CBT. We conducted logistic regression to investigate the effect on these trajectories of the BDNF Val66Met polymorphism and two different types of childhood maltreatment, abuse and neglect. Results We identified two response trajectories (“high response” and “low response”), and found that they were not significantly associated with either the genetic (BDNF Val66Met polymorphism) or childhood trauma-related variables of interest, nor with an interaction between these variables. Conclusions We found no evidence to support an effect of the BDNF gene or childhood trauma-related variables on CBT outcome in PD. Future studies in this field may benefit from looking at other genotypes or using different (e.g. whole-genome) approaches. PMID:27355213

  12. Curcumin Improves Amyloid β-Peptide (1-42 Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    Full Text Available Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer's disease (AD. However, the molecular mechanisms underlying curcumin's effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42, representing a rodent model of Alzheimer's disease (AD. The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day but not acute (once a day curcumin treatments (50, 100, and 200 mg/kg improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

  13. Involvement of BDNF/ERK signaling in spontaneous recovery from trimethyltin-induced hippocampal neurotoxicity in mice.

    Science.gov (United States)

    Lee, Sueun; Yang, Miyoung; Kim, Juhwan; Son, Yeonghoon; Kim, Jinwook; Kang, Sohi; Ahn, Wooseok; Kim, Sung-Ho; Kim, Jong-Choon; Shin, Taekyun; Wang, Hongbing; Moon, Changjong

    2016-03-01

    Trimethyltin (TMT) toxicity causes histopathological damage in the hippocampus and induces seizure behaviors in mice. The lesions and symptoms recover spontaneously over time; however, little is known about the precise mechanisms underlying this recovery from TMT toxicity. We investigated changes in the brain-derived neurotrophic factor/extracellular signal-regulated kinases (BDNF/ERK) signaling pathways in the mouse hippocampus following TMT toxicity. Mice (7 weeks old, C57BL/6) administered TMT (2.6mg/kg intraperitoneally) showed acute and severe neurodegeneration with increased TUNEL-positive cells in the dentate gyrus (DG) of the hippocampus. The mRNA and protein levels of BDNF in the hippocampus were elevated by TMT treatment. Immunohistochemical analysis showed that TMT treatment markedly increased phosphorylated ERK1/2 expression in the mouse hippocampus 1-4 days after TMT treatment, although the intensity of ERK immunoreactivity in mossy fiber decreased at 1-8 days post-treatment. In addition, ERK-immunopositive cells were localized predominantly in doublecortin-positive immature progenitor neurons in the DG. In primary cultured immature hippocampal neurons (4 days in vitro), BDNF treatment alleviated TMT-induced neurotoxicity, via activation of the ERK signaling pathway. Thus, we suggest that BDNF/ERK signaling pathways may be associated with cell differentiation and survival of immature progenitor neurons, and will eventually lead to spontaneous recovery in TMT-induced hippocampal neurodegeneration. PMID:26772626

  14. Comparing clinical responses and the biomarkers of BDNF and cytokines between subthreshold bipolar disorder and bipolar II disorder.

    Science.gov (United States)

    Wang, Tzu-Yun; Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Wang, Liang-Jen; Chen, Po See; Chen, Shih-Heng; Chu, Chun-Hsien; Huang, San-Yuan; Tzeng, Nian-Sheng; Li, Chia-Ling; Chung, Yi-Lun; Hsieh, Tsai-Hsin; Lee, I Hui; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2016-01-01

    Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naïve patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacological treatment (valproic acid, fluoxetine, risperidone, lorazepam). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical responses at baseline and at weeks 0, 1, 2, 4, 8, and 12. Inflammatory cytokines (tumour necrosis factor [TNF]-α, transforming growth factor [TGF]-β1, interleukin [IL]-6, IL-8 and IL-1β) and BDNF levels were also measured. Mixed models repeated measurement was used to examine the therapeutic effect and changes in BDNF and cytokine levels between the groups. HDRS and YMRS scores significantly (P < 0.001) declined in both groups, the SBP group had significantly lower levels of BDNF (P = 0.005) and TGF-β1 (P = 0.02). Patients with SBP and BP-II respond similarly to treatment, but SBP patients may have different neuroinflammation marker expression. PMID:27270858

  15. Does PGC1α/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders?

    Science.gov (United States)

    Jodeiri Farshbaf, Mohammad; Ghaedi, Kamran; Megraw, Timothy L; Curtiss, Jennifer; Shirani Faradonbeh, Mahsa; Vaziri, Pooneh; Nasr-Esfahani, Mohammad Hossein

    2016-03-01

    Neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases have high prevalence among the elderly. Many strategies have been established to alleviate the symptoms experienced by affected individuals. Recent studies have shown that exercise helps patients with neurological disorders to regain lost physical abilities. PGC1α/FNDC5/BDNF has emerged recently as a critical pathway for neuroprotection. PGC1α is a highly conserved co-activator of transcription factors that preserves and protects neurons against destruction. PGC1α regulates FNDC5 and its processed and secreted peptide Irisin, which has been proposed to play a critical role in energy expenditure and to promote neural differentiation of mouse embryonic stem cells. FNDC5 may also increase the expression of the neurotrophic factor BDNF, a neuroprotective agent, in the hippocampus. BDNF is secreted from hippocampus, amygdala, cerebral cortex and hypothalamus neurons and initiates intracellular signaling pathways through TrkB receptors. These pathways have positive feedback on CREB activities and lead to enhancement in PGC1α expression in neurons. Therefore, FNDC5 could behave as a key regulator in neuronal survival and development. This review presents recent findings on the PGC1α/FNDC5/BDNF pathway and its role in neuroprotection, and discusses the controversial promise of irisin as a mediator of the positive benefits of exercise. PMID:26611102

  16. Histone deacetylase activity and brain-derived neurotrophic factor (BDNF levels in a pharmacological model of mania

    Directory of Open Access Journals (Sweden)

    Laura Stertz

    2014-03-01

    Full Text Available Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH exposure, a well-accepted animal model of acute mania in bipolar disorder (BD, and histone deacetylase (HDAC inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC and peripheral blood mononuclear cells (PBMCs of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li, 200 mg/kg sodium valproate (VPT, 2 mg/kg sodium butyrate (SB, or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity.

  17. Association of Polymorphisms in BDNF, MTHFR, and Genes Involved in the Dopaminergic Pathway with Memory in a Healthy Chinese Population

    Science.gov (United States)

    Yeh, Ting-Kuang; Hu, Chung-Yi; Yeh, Ting-Chi; Lin, Pei-Jung; Wu, Chung-Hsin; Lee, Po-Lei; Chang, Chun-Yen

    2012-01-01

    The contribution of genetic factors to the memory is widely acknowledged. Research suggests that these factors include genes involved in the dopaminergic pathway, as well as the genes for brain-derived neurotrophic factor (BDNF) and methylenetetrahydrofolate reductase (MTHFR). The activity of the products of these genes is affected by single…

  18. Topological defect dynamics in operando battery nanoparticles

    Science.gov (United States)

    Ulvestad, A.; Singer, A.; Clark, J. N.; Cho, H. M.; Kim, J. W.; Harder, R.; Maser, J.; Meng, Y. S.; Shpyrko, O. G.

    2015-06-01

    Topological defects can markedly alter nanomaterial properties. This presents opportunities for “defect engineering,” where desired functionalities are generated through defect manipulation. However, imaging defects in working devices with nanoscale resolution remains elusive. We report three-dimensional imaging of dislocation dynamics in individual battery cathode nanoparticles under operando conditions using Bragg coherent diffractive imaging. Dislocations are static at room temperature and mobile during charge transport. During the structural phase transformation, the lithium-rich phase nucleates near the dislocation and spreads inhomogeneously. The dislocation field is a local probe of elastic properties, and we find that a region of the material exhibits a negative Poisson’s ratio at high voltage. Operando dislocation imaging thus opens a powerful avenue for facilitating improvement and rational design of nanostructured materials.

  19. Changes in the BDNF-immunopositive cell population of neocortical layers I and II/III after focal cerebral ischemia in rats.

    Science.gov (United States)

    Choi, Yongwon; Kang, Sung Goo; Kam, Kyung-Yoon

    2015-04-24

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is widely distributed in the central nervous system, including the cerebral cortex. BDNF plays an important role in normal neural development, survival of existing neurons, and activity-dependent neuroplasticity. BDNF can also be neuroprotective and evoke neurogenesis in certain pathological conditions, such as cerebral ischemia. Neocortical layer I is an important region that can integrate feedforward and feedback information from other cortical areas and subcortical regions. In addition, it has recently been proposed as a possible source of neuronal progenitor cells after ischemia. Therefore, we investigated changes in the BDNF-immunoreactive cell population of neocortical layers I and II/III after middle cerebral artery occlusion (MCAO)-induced cerebral ischemia in rats. In unaffected condition, the number of BDNF(+) cells in layer I was significantly less than in layer II/III in the cingulate cortex and in the motor and sensory areas. The increase in the number of BDNF(+) cells in layer I 8 days after MCAO was more remarkable than layer II/III, in all regions except the area of cingulate cortex farthest from the infarct core. Only BDNF(+)-Ox-42(+) cells showed a tendency to increase consistently toward the infarct core in both layers I and II/III, implying a major source of BDNF for response to ischemic injury. The present study suggests that some beneficial effects during recovery from ischemic injury, such as increased supportive microglia/macrophages, occur owing to a sensitive response of BDNF in layer I. PMID:25681548

  20. Exploring atomic defects in molybdenum disulphide monolayers

    KAUST Repository

    Hong, Jinhua

    2015-02-19

    Defects usually play an important role in tailoring various properties of two-dimensional materials. Defects in two-dimensional monolayer molybdenum disulphide may be responsible for large variation of electric and optical properties. Here we present a comprehensive joint experiment-theory investigation of point defects in monolayer molybdenum disulphide prepared by mechanical exfoliation, physical and chemical vapour deposition. Defect species are systematically identified and their concentrations determined by aberration-corrected scanning transmission electron microscopy, and also studied by ab-initio calculation. Defect density up to 3.5 × 10 13 cm \\'2 is found and the dominant category of defects changes from sulphur vacancy in mechanical exfoliation and chemical vapour deposition samples to molybdenum antisite in physical vapour deposition samples. Influence of defects on electronic structure and charge-carrier mobility are predicted by calculation and observed by electric transport measurement. In light of these results, the growth of ultra-high-quality monolayer molybdenum disulphide appears a primary task for the community pursuing high-performance electronic devices.

  1. Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice.

    Science.gov (United States)

    Pedrón, Valeria T; Varani, André P; Balerio, Graciela N

    2016-05-01

    In previous studies we have shown that baclofen, a selective GABAB receptor agonist, prevents the somatic expression and reestablishes the dopamine and μ-opioid receptors levels, modified during naloxone-precipitated morphine withdrawal syndrome in male and female mice. There are no previous reports regarding sex differences in the elevated plus maze (EPM) and the expression of BDNF in morphine-withdrawn mice. The present study analyses the behavioral and biochemical variations during morphine withdrawal in mice of both sexes, and whether these variations are prevented with baclofen. Swiss-Webster albino prepubertal mice received morphine (2 mg/kg, i.p.) twice daily, for 9 consecutive days. On the 10th day, one group of morphine-treated mice received naloxone (opioid receptor antagonist; 6 mg/kg, i.p.) 1 h after the last dose of morphine to precipitate withdrawal. A second group received baclofen (2 mg/kg, i.p.) before naloxone administration. The EPM behavior was measured during 15 min after naloxone injection. The expression of BDNF-positive cells was determined by immunohistochemistry. Withdrawn male mice showed a higher percentage of time spent and number of entries to the open arms compared to withdrawn female mice. Baclofen prevented this behavior in both sexes. BDNF expression decreased in the AcbC, BNST, CeC, and CA3 of the hippocampus while increased in the BLA of morphine withdrawn male. Baclofen pretreatment prevented the BDNF expression observed in morphine withdrawn male mice in all the brain areas studied except in the CeC. Baclofen prevention of the EPM behavior associated to morphine withdrawal could be partially related to changes in BDNF expression. PMID:26789010

  2. Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction.

    Science.gov (United States)

    Kim, D-M; Leem, Y-H

    2016-06-01

    Chronic stress has a detrimental effect on neurological insults, psychiatric deficits, and cognitive impairment. In the current study, chronic stress was shown to impair learning and memory functions, in addition to reducing in hippocampal Adenosine monophosphate-activated protein kinase (AMPK) activity. Similar reductions were also observed for brain-derived neurotrophic factor (BDNF), synaptophysin, and post-synaptic density-95 (PSD-95) levels, all of which was counter-regulated by a regime of regular and prolonged exercise. A 21-day restraint stress regimen (6 h/day) produced learning and memory deficits, including reduced alternation in the Y-maze and decreased memory retention in the water maze test. These effects were reversed post-administration by a 3-week regime of treadmill running (19 m/min, 1 h/day, 6 days/week). In hippocampal primary culture, phosphorylated-AMPK (phospho-AMPK) and BDNF levels were enhanced in a dose-dependent manner by 5-amimoimidazole-4-carboxamide riboside (AICAR) treatment, and AICAR-treated increase was blocked by Compound C. A 7-day period of AICAR intraperitoneal injections enhanced alternation in the Y-maze test and reduced escape latency in water maze test, along with enhanced phospho-AMPK and BDNF levels in the hippocampus. The intraperitoneal injection of Compound C every 4 days during exercise intervention diminished exercise-induced enhancement of memory improvement during the water maze test in chronically stressed mice. Also, chronic stress reduced hippocampal neurogenesis (lower Ki-67- and doublecortin-positive cells) and mRNA levels of BDNF, synaptophysin, and PSD-95. Our results suggest that regular and prolonged exercise can alleviate chronic stress-induced hippocampal-dependent memory deficits. Hippocampal AMPK-engaged BDNF induction is at least in part required for exercise-induced protection against chronic stress. PMID:26975895

  3. Imaging defects and dopants

    Directory of Open Access Journals (Sweden)

    H.Philipp Ebert

    2003-06-01

    With the invention of the transistor, a revolution in the development of semiconductor-based electronic devices began. However, even in the very early stages, the importance of defects and dopant atoms became obvious. In fact, if one incorporates the right defects and dopant atoms into semiconductor materials, one can tune their electrical properties such that optimal device characteristics are achieved. Unfortunately, counteractive defects are often also formed unintentionally during semiconductor processing, leading to unfavorable electronic properties. Considerable research efforts have, therefore, focused on understanding the nanoscale physics that governs the formation of point defects, the incorporation behavior of impurities, and their respective electronic properties.

  4. Defects in semiconductors

    CERN Document Server

    Romano, Lucia; Jagadish, Chennupati

    2015-01-01

    This volume, number 91 in the Semiconductor and Semimetals series, focuses on defects in semiconductors. Defects in semiconductors help to explain several phenomena, from diffusion to getter, and to draw theories on materials' behavior in response to electrical or mechanical fields. The volume includes chapters focusing specifically on electron and proton irradiation of silicon, point defects in zinc oxide and gallium nitride, ion implantation defects and shallow junctions in silicon and germanium, and much more. It will help support students and scientists in their experimental and theoret

  5. AT2-receptor stimulation enhances axonal plasticity after spinal cord injury by upregulating BDNF expression

    DEFF Research Database (Denmark)

    Namsolleck, Pawel; Boato, Francesco; Schwengel, Katja;

    2013-01-01

    21). Complementary experiments in primary neurons and organotypic cultures served to identify underlying mechanisms. Functional recovery and plasticity of corticospinal tract (CST) fibers following SCI were monitored after application of C21 (0,3mg/kg/dayi.p.) or vehicle for 4weeks. Organotypic co...... recovery after SCI compared to controls, and this significantly correlated with the increased the number of CST fibers caudal to the lesion site. In vitro, C21 significantly promoted reinnervation in organotypic brain slice co-cultures (+50%) and neurite outgrowth of primary neurons (+25%). C21-induced...... neurite outgrowth was absent in neurons derived from AT2R-KO mice. In primary neurons, treatment with C21 further induced RNA expression of anti-apoptotic Bcl-2 (+75.7%), brain-derived neurotrophic factor (BDNF) (+53.7%), the neurotrophin receptors TrkA (+57.4%) and TrkB (+67.9%) and a marker for neurite...

  6. Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Demontis, Ditte; Ollendorff, Mathias Kaas;

    2015-01-01

    was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which......Neurotrophic factors have been investigated in relation to depression. The aim of the present study was to widen this focus to sortilin, a receptor involved in neurotrophic signalling. The serum sortilin level was investigated in 152 individuals with depression and 216 control individuals, and...... eight genetic markers located within the SORT1 gene were successfully analysed for association with depression. Genotyping was performed using the Sequenom MassARRAY platform. All the individuals returned a questionnaire and participated in a semi-structured diagnostic interview. Sortilin levels were...

  7. School Building Defect Pattern

    Directory of Open Access Journals (Sweden)

    Mahli M.

    2014-01-01

    Full Text Available In providing a conducive learning environment for the student, the school building must be in good condition. This paper is evaluating the existing condition of primary school building in Sarawak, Malaysia. It focuses on building defects pattern for school building. The primary data collection is from the school building condition survey with involvement of 24 primary schools. The schools have been selected using simple random sampling and stratified sampling (of school age as the variable of selection. The reporting method is based on Condition Survey Protocol (CSP 1 Matrix. Data analysis covers descriptive and inferential statistics. The analysis carried out found that the overall 4,725 defects have been identified. The building defect pattern is mainly on Ground Level of 3,176 defects, the highest number of defects components found on walls (798. 16.2% defects are cracks from 11 common defects and most of all the highest score of defects based on age of the building were the building in the range of 11 to 20 years.

  8. Genetic susceptibility to family environment: BDNF Val66met and 5-HTTLPR influence depressive symptoms.

    Science.gov (United States)

    Dalton, Elizabeth D; Hammen, Constance L; Najman, Jake M; Brennan, Patricia A

    2014-12-01

    Functional genetic polymorphisms associated with Brain-Derived Neurotrophic Factor (BDNF) and serotonin (5-HTTLPR) have demonstrated associations with depression in interaction with environmental stressors. In light of evidence for biological connections between BDNF and serotonin, it is prudent to consider genetic epistasis between variants in these genes in the development of depressive symptoms. The current study examined the effects of val66met, 5-HTTLPR, and family environment quality on youth depressive symptoms in adolescence and young adulthood in a longitudinal sample oversampled for maternal depression history. A differential susceptibility model was tested, comparing the effects of family environment on depression scores across different levels of a cumulative plasticity genotype, defined as presence of both, either, or neither plasticity alleles (defined here as val66met Met and 5-HTTLPR 'S'). Cumulative plasticity genotype interacted with family environment quality to predict depression among males and females at age 15. After age 15, however, the interaction of cumulative plasticity genotype and early family environment quality was only predictive of depression among females. Results supported a differential susceptibility model at age 15, such that plasticity allele presence was associated with more or less depressive symptoms depending on valence of the family environment, and a diathesis-stress model of gene-environment interaction after age 15. These findings, although preliminary because of the small sample size, support prior results indicating interactive effects of 5-HTTLPR, val66met, and environmental stress, and suggest that family environment may have a stronger influence on genetically susceptible women than men. PMID:25347540

  9. Exercise therapy normalizes BDNF upregulation and glial hyperactivity in a mouse model of neuropathic pain.

    Science.gov (United States)

    Almeida, Cayo; DeMaman, Aline; Kusuda, Ricardo; Cadetti, Flaviane; Ravanelli, Maria Ida; Queiroz, André L; Sousa, Thais A; Zanon, Sonia; Silveira, Leonardo R; Lucas, Guilherme

    2015-03-01

    Treatment of neuropathic pain is a clinical challenge likely because of the time-dependent changes in many neurotransmitter systems, growth factors, ionic channels, membrane receptors, transcription factors, and recruitment of different cell types. Conversely, an increasing number of reports have shown the ability of extended and regular physical exercise in alleviating neuropathic pain throughout a wide range of mechanisms. In this study, we investigate the effect of swim exercise on molecules associated with initiation and maintenance of nerve injury-induced neuropathic pain. BALB/c mice were submitted to partial ligation of the sciatic nerve followed by a 5-week aerobic exercise program. Physical training reversed mechanical hypersensitivity, which lasted for an additional 4 weeks after exercise interruption. Swim exercise normalized nerve injury-induced nerve growth factor, and brain-derived neurotrophic factor (BDNF) enhanced expression in the dorsal root ganglion, but had no effect on the glial-derived neurotrophic factor. However, only BDNF remained at low levels after exercise interruption. In addition, exercise training significantly reduced the phosphorylation status of PLCγ-1, but not CREB, in the spinal cord dorsal horn in response to nerve injury. Finally, prolonged swim exercise reversed astrocyte and microglia hyperactivity in the dorsal horn after nerve lesion, which remained normalized after training cessation. Together, these results demonstrate that exercise therapy induces long-lasting analgesia through various mechanisms associated with the onset and advanced stages of neuropathy. Moreover, the data support further studies to clarify whether appropriate exercise intensity, volume, and duration can also cause long-lasting pain relief in patients with neuropathic pain. PMID:25687543

  10. Defects at oxide surfaces

    CERN Document Server

    Thornton, Geoff

    2015-01-01

    This book presents the basics and characterization of defects at oxide surfaces. It provides a state-of-the-art review of the field, containing information to the various types of surface defects, describes analytical methods to study defects, their chemical activity and the catalytic reactivity of oxides. Numerical simulations of defective structures complete the picture developed. Defects on planar surfaces form the focus of much of the book, although the investigation of powder samples also form an important part. The experimental study of planar surfaces opens the possibility of applying the large armoury of techniques that have been developed over the last half-century to study surfaces in ultra-high vacuum. This enables the acquisition of atomic level data under well-controlled conditions, providing a stringent test of theoretical methods. The latter can then be more reliably applied to systems such as nanoparticles for which accurate methods of characterization of structure and electronic properties ha...

  11. Cosmic defects and cosmology

    CERN Document Server

    Magueijo, J; Magueijo, Joao; Brandenberger, Robert

    2000-01-01

    We provide a pedagogical overview of defect models of structure formation. We first introduce the concept of topological defect, and describe how to classify them. We then show how defects might be produced in phase transitions in the Early Universe and approach non-pathological scaling solutions. A very heuristic account of structure formation with defects is then provided, following which we introduce the tool box required for high precision calculations of CMB and LSS power spectra in these theories. The decomposition into scalar vector and tensor modes is reviewed, and then we introduce the concept of unequal-time correlator. We use isotropy and causality to constrain the form of these correlators. We finally show how these correlators may be decomposed into eigenmodes, thereby reducing a defect problem to a series of ``inflation'' problems. We conclude with a short description of results in these theories and how they fare against observations. We finally describe yet another application of topological d...

  12. Defect chemistry and oxygen transport of (La0.6Sr0.4 − xMx)0.99Co0.2Fe0.8O3 − δ, M = Ca (x = 0.05, 0.1), Ba (x = 0.1, 0.2), Sr: Part II: Oxygen transport

    DEFF Research Database (Denmark)

    Dalslet, Bjarke Thomas; Søgaard, Martin; Hendriksen, Peter Vang

    This paper is the second part of a two part series, where the effects of varying the A-site dopant on the defect chemistry and transport properties of the materials (La0.6Sr0.4 − xMx)0.99Co0.2Fe0.8O3 − δ, M = Sr, Ca (x = 0.05, 0.1), Ba (x = 0.1, 0.2) (LSMFC) have been investigated. In part I, the...... electrolyte probe were used to extract the permeability and surface resistance, rs. The highest permeability was found for (La0.6Sr0.3Ca0.1)0.99Co0.2Fe0.8O3 − δ. The apparent activation energy of the permeability was 78 kJ/mol. The inverse surface resistance, rs− 1, also had an activated behavior with an...... activation energy close to 180 kJ/mol for most of the materials. A reversible transition to an abnormally low rs was found in (La0.6Sr0.3Ca0.1)0.99Co0.2Fe0.8O3 − δ at T > 1223 K....

  13. Glycyrrhiza uralensis flavonoids inhibit brain microglial cell TNF-α secretion, p-IκB expression, and increase brain-derived neurotropic factor (BDNF secretion

    Directory of Open Access Journals (Sweden)

    Sangita P. Patil

    2014-07-01

    Conclusion: ASHMI and its effective flavonoid, isoliquiritigenin, inhibited TNF-α production by LPS stimulated microglial cells and elevated BDNF levels, which may prove to have anti-CNS inflammatory and anti-anxiety effects.

  14. Aging and depression vulnerability interaction results in decreased serotonin innervation associated with reduced BDNF levels in hippocampus of rats bred for learned helplessness

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders B; Santini, Martin A;

    2010-01-01

    Epidemiological studies have revealed a strong genetic contribution to the risk for depression. Both reduced hippocampal serotonin neurotransmission and brain-derived neurotrophic factor (BDNF) levels have been associated with increased depression vulnerability and are also regulated during aging...

  15. Expression of BDNF and TrkB Phosphorylation in the Rat Frontal Cortex During Morphine Withdrawal are NO Dependent.

    Science.gov (United States)

    Peregud, Danil I; Yakovlev, Alexander A; Stepanichev, Mikhail Yu; Onufriev, Mikhail V; Panchenko, Leonid F; Gulyaeva, Natalia V

    2016-08-01

    Nitric oxide (NO) mediates pharmacological effects of opiates including dependence and abstinence. Modulation of NO synthesis during the induction phase of morphine dependence affects manifestations of morphine withdrawal syndrome, though little is known about mechanisms underlying this phenomenon. Neurotrophic and growth factors are involved in neuronal adaptation during opiate dependence. NO-dependent modulation of morphine dependence may be mediated by changes in expression and activity of neurotrophic and/or growth factors in the brain. Here, we studied the effects of NO synthesis inhibition during the induction phase of morphine dependence on the expression of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and insulin-like growth factor 1 (IGF1) as well as their receptors in rat brain regions after spontaneous morphine withdrawal in dependent animals. Morphine dependence in rats was induced within 6 days by 12 injections of morphine in increasing doses (10-100 mg/kg), and NO synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) (10 mg/kg) was given 1 h before each morphine injection. The expression of the BDNF, GDNF, NGF, IGF1, and their receptors in the frontal cortex, striatum, hippocampus, and midbrain was assessed 40 h after morphine withdrawal. L-NAME treatment during morphine intoxication resulted in an aggravation of the spontaneous morphine withdrawal severity. Morphine withdrawal was accompanied by upregulation of BDNF, IGF1, and their receptors TrkB and IGF1R, respectively, on the mRNA level in the frontal cortex, and only BDNF in hippocampus and midbrain. L-NAME administration during morphine intoxication decreased abstinence-induced upregulation of these mRNAs in the frontal cortex, hippocampus and midbrain. L-NAME prevented from abstinence-induced elevation of mature but not pro-form of BDNF polypeptide in the frontal cortex. While morphine abstinence did not affect Trk

  16. Dysregulation of BDNF-TrkB Signaling in Developing Hippocampal Neurons by Pb2+: Implications for an Environmental Basis of Neurodevelopmental Disorders

    OpenAIRE

    Stansfield, Kirstie H.; Pilsner, J. Richard; Lu, Quan; Wright, Robert O.; Guilarte, Tomás R.

    2012-01-01

    Dysregulation of synaptic development and function has been implicated in the pathophysiology of neurodegenerative disorders and mental disease. A neurotrophin that has an important function in neuronal and synaptic development is brain-derived neurotrophic factor (BDNF). In this communication, we examined the effects of lead (Pb2+) exposure on BDNF-tropomyosin-related kinase B (TrkB) signaling during the period of synaptogenesis in cultured neurons derived from embryonic rat hippocampi. We s...

  17. Abnormal hippocampal BDNF and miR-16 expression is associated with depression-like behaviors induced by stress during early life.

    Directory of Open Access Journals (Sweden)

    Mei Bai

    Full Text Available Some environmental stressors lead to the onset of depression via inhibiting hippocampal BDNF expression, but other environmental stressors-induced depression exhibits no change in BDNF expression. The underlying mechanisms behind the divergence remain unknown. In this study, depression-like behaviors were induced in rats by maternal deprivation (MD and chronic unpredictable stress (CUPS. Depression-like behaviors were tested by open field test, forced swimming test, and sucrose consumption test. BDNF and miR-16 expressions in the hippocampus were examined by real-time PCR. MD and CUPS rats crawled less distance, exhibited decreased vertical activity, and produced more fecal pellets than control rats in the open field test. However, MD rats crawled less distance and produced significantly less fecal pellets than CUPS rats. In the forced swimming and sucrose consumption tests, CUPS and MD rats exhibited longer floating time and consumed less sucrose than control rats, but MD rats exhibited shorter floating time and consumed less sucrose than CUPS rats. MD but not CUPS rats showed lower BDNF mRNA and higher miR-16 expression than control rats. In MD rats, BDNF mRNA expression negatively correlated with the expression of miR-16. BDNF expression positively correlated with the total distance rats crawled and vertical activity in the open field test while miR-16 expression negatively correlated the two behaviors. BDNF positively correlated with sucrose preference rate while miR-16 negatively correlated with sucrose preference rate of the sucrose consumption test. Our study suggests that MD and CUPS induced different depression-like behaviors in rats. Depression induced by MD but not CUPS was significantly associated with upregulation of miR-16 and possibly subsequent downregulation of BDNF in hippocampus.

  18. 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders

    OpenAIRE

    Liu, Chaoyang; Chan, Chi Bun; Ye, Keqiang

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates a variety of biological processes predominantly via binding to the transmembrane receptor tyrosine kinase TrkB. It is a potential therapeutic target in numerous neurological, mental and metabolic disorders. However, the lack of efficient means to deliver BDNF into the body imposes an insurmountable hurdle to its clinical application. To address this challenge, we initiated a cell-based drug screening to search for small molecules that act as ...

  19. Brain-derived neurotrophic factor (BDNF) gene: a gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?

    OpenAIRE

    Laing, Katharine R.; Mitchell, David; Wersching, Heike; Czira, Maria E.; Berger, Klaus; Baune, Bernhard T

    2011-01-01

    Cognitive aging processes are underpinned by multiple processes including genetic factors. The brain-derived neurotrophic factor (BDNF) has been suggested to be involved in age-related cognitive decline in otherwise healthy individuals. The gender-specific role of the BDNF gene in cognitive aging remains unclear. The identification of genetic biomarkers might be a useful approach to identify individuals at risk of cognitive decline during healthy aging processes. The aim of this study was to ...

  20. GLIA DETERMINE THE COURSE OF BDNF-MEDIATED DENDRITOGENESIS AND PROVIDE A SOLUBLE INHIBITORY CUE TO DENDRITIC GROWTH IN THE BRAINSTEM

    Science.gov (United States)

    Martin, Jessica L.; Brown, Alexandra L.; Balkowiec, Agnieszka

    2012-01-01

    Cardiorespiratory control neurons in the brainstem nucleus tractus solitarius (NTS) undergo dramatic expansion of dendritic arbors during the early postnatal period, when functional remodeling takes place within the NTS circuitry. However, the underlying molecular mechanisms of morphological maturation of NTS neurons are largely unknown. Our previous studies point to the neurotrophin brain-derived neurotrophic factor (BDNF), which is abundantly expressed by NTS-projecting primary sensory neurons, as a candidate mediator of NTS dendritogenesis. In the current study, we used neonatal rat NTS neurons in vitro to examine the role of BDNF in the dendritic development of neurochemically-identified subpopulations of NTS neurons. In the presence of abundant glia, BDNF promoted NTS dendritic outgrowth and complexity, with the magnitude of the BDNF effect dependent on neuronal phenotype. Surprisingly, BDNF switched from promoting to inhibiting NTS dendritogenesis upon glia depletion. Moreover, glia depletion alone led to a significant increase in NTS dendritic outgrowth. Consistent with this result, astrocyte-conditioned medium (ACM), which promoted hippocampal dendritogenesis, inhibited dendritic growth of NTS neurons. The latter effect was abolished by heat-inactivation of ACM, pointing to a diffusible astrocyte-derived negative regulator of NTS dendritic growth. Together, these data demonstrate a role for BDNF in the postnatal development of NTS neurons, and reveal novel effects of glia on this process. Moreover, previously documented dramatic increases in NTS glial proliferation in victims of sudden infant death syndrome (SIDS) underscore the importance of our findings and the need to better understand the role of glia and their interactions with BDNF during NTS circuit maturation. Furthermore, while it has previously been demonstrated that the specific effects of BDNF on dendritic growth are context-dependent, the role of glia in this process is unknown. Thus, our data

  1. Software Defect Association Mining and Defect Correction Effort Prediction

    OpenAIRE

    Song, Q; Shepperd, MJ; Cartwright, MH; Mair, C.

    2006-01-01

    Much current software defect prediction work concentrates on the number of defects remaining in software system. In this paper, we present association rule mining based methods to predict defect associations and defect-correction effort. This is to help developers detect software defects and assist project managers in allocating testing resources more effectively. We applied the proposed methods to the SEL defect data consisting of more than 200 projects over more than 15 years. The results s...

  2. Assessment of fuel defects in Darlington NGS

    International Nuclear Information System (INIS)

    This paper outlines a safety analysis of the defect status of Darlington-1 during the operating period August to October 1991. The models used are outlined, and their implementation is described. The results of the analysis indicate that the number of defected fuel elements never exceeded three in the north primary heat transport loop, and the mass of tramp uranium was ∼2 grams during the period in question. These results are within Ontario Hydro's experience with new reactors. 6 refs., 3 figs., 2 tabs

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

    Directory of Open Access Journals (Sweden)

    Emmanouil Rizos

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

  4. Conditioned taste aversion prevents the long-lasting BDNF-induced enhancement of synaptic transmission in the insular cortex: A metaplastic effect.

    Science.gov (United States)

    Rivera-Olvera, Alejandro; Rodríguez-Durán, Luis F; Escobar, Martha L

    2016-04-01

    Homeostatic plasticity mechanisms dynamically adjust synaptic strengths to promote stability that is crucial for memory storage. Metaplasticity is an example of these forms of plasticity that modify the capacity of synapses to experience subsequent Hebbian modifications. In particular, training in several behavioral tasks modifies the ability to induce long-term potentiation (LTP). Recently, we have reported that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP generated by high frequency stimulation in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC). One of the key molecular players that underlie long-term synaptic plasticity is brain-derived neurotrophic factor (BDNF). Previous studies from our group reported that acute microinfusion of BDNF in the IC induces a lasting potentiation of synaptic efficacy at the Bla-IC projection. Thus, the aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent BDNF-induced potentiation of synaptic transmission in the Bla-IC projection in vivo. Accordingly, CTA trained rats received intracortical microinfusion of BDNF in order to induce lasting potentiation 48h after the aversion test. Our results show that CTA training prevents the induction of in vivo BDNF-LTP in the Bla-IC projection. The present results provide evidence that CTA modulates BDNF-dependent changes in IC synaptic strength. PMID:26854904

  5. BDNF polymorphisms are linked to poorer working memory performance, reduced cerebellar and hippocampal volumes and differences in prefrontal cortex in a Swedish elderly population.

    Directory of Open Access Journals (Sweden)

    Samantha J Brooks

    Full Text Available BACKGROUND: Brain-derived neurotrophic factor (BDNF links learning, memory and cognitive decline in elderly, but evidence linking BDNF allele variation, cognition and brain structural differences is lacking. METHODS: 367 elderly Swedish men (n = 181 and women (n = 186 from Prospective Investigation of the Vasculature in Uppsala seniors (PIVUS were genotyped and the BDNF functional rs6265 SNP was further examined in subjects who completed the Trail Making Task (TMT, verbal fluency task, and had a magnetic resonance imaging (MRI scan. Voxel-based morphometry (VBM examined brain structure, cognition and links with BDNF. RESULTS: The functional BDNF SNP (rs6265, predicted better working memory performance on the TMT with positive association of the Met rs6265, and was linked with greater cerebellar, precuneus, left superior frontal gyrus and bilateral hippocampal volume, and reduced brainstem and bilateral posterior cingulate volumes. CONCLUSIONS: The functional BDNF polymorphism influences brain volume in regions associated with memory and regulation of sensorimotor control, with the Met rs6265 allele potentially being more beneficial to these functions in the elderly.

  6. Hydrogen Sulfide Protects against Chronic Unpredictable Mild Stress-Induced Oxidative Stress in Hippocampus by Upregulation of BDNF-TrkB Pathway

    Science.gov (United States)

    Zou, Wei; Wang, Chun-Yan; Tan, Hui-Ying; Zeng, Hai-Ying; Zhang, Ping; Gu, Hong-Feng

    2016-01-01

    Chronic unpredictable mild stress (CUMS) induces hippocampal oxidative stress. H2S functions as a neuroprotectant against oxidative stress in brain. We have previously shown the upregulatory effect of H2S on BDNF protein expression in the hippocampus of rats. Therefore, we hypothesized that H2S prevents CUMS-generated oxidative stress by upregulation of BDNF-TrkB pathway. We showed that NaHS (0.03 or 0.1 mmol/kg/day) ameliorates the level of hippocampal oxidative stress, including reduced levels of malondialdehyde (MDA) and 4-hydroxy-2-trans-nonenal (4-HNE), as well as increased level of glutathione (GSH) and activity of superoxide dismutase (SOD) in the hippocampus of CUMS-treated rats. We also found that H2S upregulated the level of BDNF and p-TrkB protein in the hippocampus of CUMS rats. Furthermore, inhibition of BDNF signaling by K252a, an inhibitor of the BDNF receptor TrkB, blocked the antioxidant effects of H2S on CUMS-induced hippocampal oxidative stress. These results reveal the inhibitory role of H2S in CUMS-induced hippocampal oxidative stress, which is through upregulation of BDNF/TrkB pathway. PMID:27525050

  7. Neural tube defects

    OpenAIRE

    M.E. Marshall

    1981-01-01

    Neural tube defects refer to any defect in the morphogenesis of the neural tube, the most common types being spina bifida and anencephaly. Spina bifida has been recognised in skeletons found in north-eastern Morocco and estimated to have an age of almost 12 000 years. It was also known to the ancient Greek and Arabian physicians who thought that the bony defect was due to the tumour. The term spina bifida was first used by Professor Nicolai Tulp of Amsterdam in 1652. Many other terms have bee...

  8. Defect solitons in photonic lattices.

    Science.gov (United States)

    Yang, Jianke; Chen, Zhigang

    2006-02-01

    Nonlinear defect modes (defect solitons) and their stability in one-dimensional photonic lattices with focusing saturable nonlinearity are investigated. It is shown that defect solitons bifurcate out from every infinitesimal linear defect mode. Low-power defect solitons are linearly stable in lower bandgaps but unstable in higher bandgaps. At higher powers, defect solitons become unstable in attractive defects, but can remain stable in repulsive defects. Furthermore, for high-power solitons in attractive defects, we found a type of Vakhitov-Kolokolov (VK) instability which is different from the usual VK instability based on the sign of the slope in the power curve. Lastly, we demonstrate that in each bandgap, in addition to defect solitons which bifurcate from linear defect modes, there is also an infinite family of other defect solitons which can be stable in certain parameter regimes. PMID:16605473

  9. Screening Tests for Birth Defects

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Screening Tests for Birth Defects Home For Patients Search ... for Birth Defects FAQ165, April 2014 PDF Format Screening Tests for Birth Defects Pregnancy What is a ...

  10. Defect forces, defect couples and path integrals

    International Nuclear Information System (INIS)

    Definition and meaning of concepts like 'J integral' are given without any assumption about material behaviour. The key of the work is the field of 'defect forces' and 'defect couples' in a continuous media. These forces and couples, which can also be called 'material forces' and 'material couples' are related to the work done by a particle moving through a solid. It is shown that the resultant of all the defect forces included in a volume is the Jsub(k) integral computer on the surface surrounding this volume. A similar result is obtained about the moment resultant. Conventional form of the principle of virtual work is not applicable to fractures mechanics because equations of compatibility are not satisfied. A generalized form is given, which is valid when (virtual) crack propagation is considered. The virtual work of 'material' forces is included in the generalized form, and can be used as a new definition of J concept. As an illustration application, a simple procedure is described which allows to obtain the curve J-Δa (the so called J-R curve) from only one experimental test

  11. Defect Prevention Based on 5 Dimensions of Defect Origin

    Directory of Open Access Journals (Sweden)

    Sakthi Kumaresh

    2012-08-01

    Full Text Available “Discovering the unexpected is more important than confirming the known [7]. In software development,the “unexpected” one relates to defects. These defects when unattended would cause failure to the productand risk to the users. The increasing dependency of society on software and the crucial consequences that afailure can cause requires the need to find out the defects at the origin itself. Based on the lessons learntfrom the earlier set of projects, a defect framework highlighting the 5 Dimensions (Ds of defect origin isproposed in this work. The defect framework is based on analyzing the defects that had emerged fromvarious stages of software development like Requirements, Design, Coding, Testing and Timeline (defectsdue to lack of time during development. This study is not limited to just identifying the origin of defects atvarious phases of software development but also finds out the reasons for such defects, and defectpreventive (DP measures are proposed for each type of defect. This work can help practitioners chooseeffective defect avoidance measures.In addition to arriving at defect framework, this work also proposes a defect injection metric based onseverity of the defect rather than just defect count, which gives the number of adjusted defects produced bya project at various phases. The defect injection metric value, once calculated, serves as a yardstick tomake a comparison in the improvements made in the software process development between similar set ofprojects

  12. Behavioral phenotype and BDNF differences related to apoE isoforms and sex in young transgenic mice

    DEFF Research Database (Denmark)

    Reverte, Ingrid; Klein, Anders Bue; Ratner, Cecilia;

    2012-01-01

    , very little information is available on apoE2 genotype. In the present study, we have characterized behavioral and learning phenotypes in young transgenic mice apoE2, apoE3 and apoE4 of both sexes. We have also determined the levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in...... exploration of an open-field, which is compatible with a hyperactive behavior, was found in apoE2 females, while a decreased activity was observed in apoE4 mice. Increased BDNF levels in the frontal cortex were observed in apoE2 mice compared to apoE3. These results underscore behavioral differences between...

  13. Electronic properties of multi-defected zigzag carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Electronic properties of multi-defected zigzag single-walled carbon nanotubes are investigated by use of the tight-binding Green’s function method. The Stone-Wales defects and the vacancies are considered. We find that the conductance sensitively depends on the realistic defect configurations for the metallic zigzag carbon nanotubes. Interestingly, the electronic transport properties of the nanotubes with three vacancies can be considered as the sum effect of two double-vacancies, while those with Stone-Wales defects can not. The electron interference along the longitudinal axis and the transport blocking are observed, which may be useful for understanding the electron transport behavior of carbon nanotube in experiments.

  14. Birth Defects (For Parents)

    Science.gov (United States)

    ... KidsHealth in the Classroom What Other Parents Are Reading Upsetting News Reports? What to Say Vaccines: Which ... there is a problem with a baby's body chemistry, it is called a metabolic birth defect. Metabolic ...

  15. Neural tube defects

    Directory of Open Access Journals (Sweden)

    M.E. Marshall

    1981-09-01

    Full Text Available Neural tube defects refer to any defect in the morphogenesis of the neural tube, the most common types being spina bifida and anencephaly. Spina bifida has been recognised in skeletons found in north-eastern Morocco and estimated to have an age of almost 12 000 years. It was also known to the ancient Greek and Arabian physicians who thought that the bony defect was due to the tumour. The term spina bifida was first used by Professor Nicolai Tulp of Amsterdam in 1652. Many other terms have been used to describe this defect, but spina bifida remains the most useful general term, as it describes the separation of the vertebral elements in the midline.

  16. Point defects in platinum

    International Nuclear Information System (INIS)

    An investigation was made of the mobility and types of point defect introduced in platinum by deformation in liquid nitrogen, quenching into water from 1600oC, or reactor irradiation at 50oC. In all cases the activation energy for motion of the defect was determined from measurements of electrical resistivity. Measurements of density, hardness, and x-ray line broadening were also made there applicable. These experiments indicated that the principal defects remaining in platinum after irradiation were single vacant lattice sites and after quenching were pairs of vacant lattice sites. Those present after deformation In liquid nitrogen were single vacant lattice sites and another type of defect, perhaps interstitial atoms. (author)

  17. Quantum computing with defects

    OpenAIRE

    Weber, J R; Koehl, W. F.; Varley, J. B.; Janotti, A.; Buckley, B. B.; Van de Walle, C. G.; Awschalom, D. D.

    2010-01-01

    Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV-1) center stands out for its robustness - its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar qua...

  18. Anomalies and developmental defects

    International Nuclear Information System (INIS)

    Amonalies and developmental defects in trachea and bronchi (tracheal bronch us, diverticulum of trachea or bronchus, defects due to atresia of bronchial tre e, tracheobronchomegaly), lung vessels (aneurisms of pulmonary artery, agenesia, aplasia and hypoplasia of pulmonary artery,anomalies of pulmonary veins, varico sis of pulmonary veins), pulmonary tissue (lung sequestration, congenital lobar pulmonary emphysema, essential hemosiderosis), have beendescribed. The problems of the diagnosis of the above-mentioned diseases using roentgenograms are consid ered

  19. Neural Tube Defects

    OpenAIRE

    Greene, Nicholas D. E.; Copp, Andrew J.

    2014-01-01

    Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechani...

  20. Signatures of Topological Defects

    OpenAIRE

    Berezinsky, V. S.; P. Blasi(INAF Arcetri); Vilenkin, A.

    1998-01-01

    We argue that due to various restrictions cosmic strings and monopole-string networks are not likely to produce the observed flux of ultra-high energy cosmic rays (UHECR). Among the topological defects studied so far, the most promising UHECR sources are necklaces and monopolonia. Other viable sources which are similar to topological defects are relic superheavy particles. All these sources have an excess of pions (and thus photons) over nucleons at production. We demonstrate that in the case...

  1. Brain-Derived Neurotrophic Factor (BDNF) Promotes Cochlear Spiral Ganglion Cell Survival and Function in Deafened, Developing Cats

    OpenAIRE

    Leake, Patricia A.; Hradek, Gary T.; Hetherington, Alexander M.; Stakhovskaya, Olga

    2011-01-01

    Postnatal development and survival of spiral ganglion (SG) neurons depend upon both neural activity and neurotrophic support. Our previous studies showed that electrical stimulation from a cochlear implant only partly prevents SG degeneration after early deafness. Thus, neurotrophic agents that might be combined with an implant to improve neural survival are of interest. Recent studies reporting that BDNF promotes SG survival after deafness, have been conducted in rodents and limited to relat...

  2. Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression

    OpenAIRE

    Gómez-Casati, Maria E; MURTIE, JOSHUA C.; Rio, Carlos; Stankovic, Konstantina; Liberman, M. Charles; Corfas, Gabriel

    2010-01-01

    Recent studies indicate that molecules released by glia can induce synapse formation. However, what induces glia to produce such signals, their identity, and their in vivo relevance remain poorly understood. Here we demonstrate that supporting cells of the vestibular organ—cells that have many characteristics of glia—promote synapse formation only when induced by neuron-derived signals. Furthermore, we identify BDNF as the synaptogenic signal produced by these nonneuronal cells. Mice in which...

  3. Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK-801 Administration

    OpenAIRE

    Chunmei Guo; Yang Yang; Yun'ai Su; Tianmei Si

    2010-01-01

    Neonatal blockade of N-methyl-D-aspartic acid (NMDA) receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF) expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND) 5 through 14. Open-field test was perfo...

  4. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF

    OpenAIRE

    Laura L. Hurley; Akinfiresoye, Luli; Nwulia, Evaristus; Kamiya, Atsushi; Kulkarni, Amol; Tizabi, Yousef

    2012-01-01

    Curcumin is the principal active ingredient found in turmeric (Curcuma longa), a plant used in traditional Asian diets and herbal medicines. It is known to have a wide range of biological actions including antidepressant-like effects which have been observed in stress-induced depression models. This study was designed to investigate the antidepressant potential of curcumin in a non-induced model of depression. Moreover, since brain derived neurotrophic factor (BDNF) has been implicated in ant...

  5. BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress.

    Science.gov (United States)

    Wang, Jun-Ming; Yang, Lian-He; Zhang, Yue-Yue; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

    2015-11-01

    Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain. PMID:26255123

  6. Neuropeptide S and BDNF gene expression in the amygdala are influenced by social decision-making under stress.

    Science.gov (United States)

    Smith, Justin P; Achua, Justin K; Summers, Tangi R; Ronan, Patrick J; Summers, Cliff H

    2014-01-01

    In a newly developed conceptual model of stressful social decision-making, the Stress-Alternatives Model (SAM; used for the 1st time in mice) elicits two types of response: escape or remain submissively. Daily (4d) aggressive social interaction in a neutral arena between a C57BL6/N test mouse and a larger, novel aggressive CD1 mouse, begin after an audible tone (conditioned stimulus; CS). Although escape holes (only large enough for smaller test animals) are available, and the aggressor is unremittingly antagonistic, only half of the mice tested utilize the possibility of escape. During training, for mice that choose to leave the arena and social interaction, latency to escape dramatically decreases over time; this is also true for control C57BL6/N mice which experienced no aggression. Therefore, the open field of the SAM apparatus is intrinsically anxiogenic. It also means that submission to the aggressor is chosen despite this anxiety and the high intensity of the aggressive attacks and defeat. While both groups that received aggression displayed stress responsiveness, corticosterone levels were significantly higher in animals that chose submissive coexistence. Although both escaping and non-escaping groups of animals experienced aggression and defeat, submissive animals also exhibited classic fear conditioning, freezing in response to the CS alone, while escaping animals did not. In the basolateral amygdala (BLA), gene expression of brain-derived neurotrophic factor (BDNF) was diminished, at the same time neuropeptide S (NPS) expression was significantly elevated, but only in submissive animals. This increase in submission-evoked NPS mRNA expression was greatest in the central amygdala (CeA), which coincided with decreased BDNF expression. Reduced expression of BDNF was only found in submissive animals that also exhibit elevated NPS expression, despite elevated corticosterone in all socially interacting animals. The results suggest an interwoven relationship

  7. Neuropeptide S and BDNF gene expression in the amygdala are influenced by social decision-making under stress

    Directory of Open Access Journals (Sweden)

    Justin P. Smith

    2014-04-01

    Full Text Available In a newly developed conceptual model of stressful social decision making, the Stress-Alternatives Model (SAM; used for the 1st time in mice elicits two types of response: escape or remain submissively. Daily (4d aggressive social interaction in a neutral arena between a C57BL6/N test mouse and a larger, novel aggressive CD1 mouse, begin after an audible tone (conditioned stimulus; CS. Although escape holes (only large enough for smaller test animals are available, and the aggressor is unremittingly antagonistic, only half of the mice tested utilize the possibility of escape. During training, for mice that choose to leave the arena and social interaction, latency to escape dramatically decreases over time; this is also true for control C57BL6/N mice which experienced no aggression. Therefore, the open field of the SAM apparatus is intrinsically anxiogenic. It also means that submission to the aggressor is chosen despite this anxiety and the high intensity of the aggressive attacks and defeat. While both groups that received aggression displayed stress responsiveness, corticosterone levels were significantly higher in animals that chose submissive coexistence. Although both escaping and non-escaping groups of animals experienced aggression and defeat, submissive animals also exhibited classic fear conditioning, freezing in response to the CS alone, while escaping animals did not. In the basolateral amygdala, gene expression of BDNF was diminished, but NPS expression was significantly elevated, but only in submissive animals. This increase in submission-evoked NPS mRNA expression was greatest in the central amygdala, which coincided with decreased BDNF expression. Reduced expression of BDNF is only in submissive animals that also exhibit elevated NPS expression, despite elevated corticosterone in all socially interacting animals. The results suggest an interwoven relationship, linked by social context, between amygdalar BDNF, NPS and plasma

  8. Comparing clinical responses and the biomarkers of BDNF and cytokines between subthreshold bipolar disorder and bipolar II disorder

    OpenAIRE

    Tzu-Yun Wang; Sheng-Yu Lee; Shiou-Lan Chen; Yun-Hsuan Chang; Liang-Jen Wang; Po See Chen; Shih-Heng Chen; Chun-Hsien Chu; San-Yuan Huang; Nian-Sheng Tzeng; Chia-Ling Li; Yi-Lun Chung; Tsai-Hsin Hsieh; I Hui Lee; Kao Chin Chen

    2016-01-01

    Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naïve patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacologica...

  9. Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis

    OpenAIRE

    Hosang, Georgina M; Shiles, Celia; Tansey, Katherine E; McGuffin, Peter; Uher, Rudolf

    2014-01-01

    Background Major depression is a disabling psychiatric illness with complex origins. Life stress (childhood adversity and recent stressful events) is a robust risk factor for depression. The relationship between life stress and Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has received much attention. The aim of the present work was to review and conduct a meta-analysis on the results from published studies examining this interaction. Methods A literatur...

  10. NC-03POLYMORPHISMS IN THE COMT, BDNF AND DTNBP1 GENES AND COGNITIVE FUNCTIONS IN PATIENTS WITH BRAIN TUMORS

    OpenAIRE

    Correa, Denise; Satagopan, Jaya; Baser, Raymond; Cheung, Kenneth; DeAngelis, Lisa; Orlow, Irene

    2014-01-01

    BACKGROUND: Cognitive dysfunction is prevalen among brain tumor patients treated with radiotherapy (RT) and chemotherapy (CT). However, little is known about genetic risk factors that may moderate their vulnerability for developing cognitive impairment. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in three genes, Catechol-O-Methyl-Transferase (COMT), Brain-Derived-Neurotrophic-Factor (BDNF), and dystrobrevin binding protein 1 (DTNBP1), and cognitive fun...

  11. Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms

    OpenAIRE

    Erickson, Kirk I.; Suever, Barbara L.; B. Magnus Francis; Kramer, Arthur F.

    2008-01-01

    Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single-nucleotide polymorphism (SNP) in the COMT (Val158/108Met) gene affects the concentration of d...

  12. Effect of Chronic Restraint Stress on HPA Axis Activity and Expression of BDNF and Trkb in the Hippocampus of Pregnant Rats: Possible Contribution in Depression during Pregnancy and Postpartum Period

    OpenAIRE

    Maghsoudi, Nader; Ghasemi, Rasoul; Ghaempanah, Zahra; Ardekani, Ali M.; Nooshinfar, Elahe; Tahzibi, Abbas

    2014-01-01

    Introduction Brain-Derived Neurotrophic Factor (BDNF) and its receptor, TrkB, in the hippocampus are targets for adverse effects of stress paradigms; in addition, BDNF and its receptor play key role in the pathology of brain diseases like depression. In the present study, we evaluated the possible role of hippocampal BDNF in depression during pregnancy, Methods To achieve the purpose, repeated restrain stress (1 or 3 hours daily for 7 days) during the last week of pregnancy was used and alter...

  13. Higher reward value of starvation imagery in anorexia nervosa and association with the Val66Met BDNF polymorphism.

    Science.gov (United States)

    Clarke, J; Ramoz, N; Fladung, A-K; Gorwood, P

    2016-01-01

    Recent studies support the idea that abnormalities of the reward system contribute to onset and maintenance of anorexia nervosa (AN). Next to cues coding for overweight, other research suggest cues triggering the proposed starvation dependence to be pivotally involved in the AN pathogenesis. We assessed the characteristics of the cognitive, emotional and physiologic response toward disease-specific pictures of female body shapes, in adult AN patients compared with healthy control (HC) women. Frequency and amplitude of skin conductance response (SCR) in 71 patients with AN and 20 HC were registered during processing of stimuli of three weight categories (over-, under- and normal weight). We then assessed the role of the Val66Met BDNF polymorphism as a potential intermediate factor. AN patients reported more positive feelings during processing of underweight stimuli and more negative feelings for normal- and overweight stimuli. The SCR showed a group effect (P=0.007), AN patients showing overall higher frequency of the response. SCR within patients was more frequent during processing of underweight stimuli compared with normal- and overweight stimuli. The Met allele of the BDNF gene was not more frequent in patients compared with controls, but was associated to an increased frequency of SCR (P=0.008) in response to cues for starvation. A higher positive value of starvation, rather than more negative one of overweight, might more accurately define females with AN. The Met allele of the BDNF gene could partly mediate the higher reward value of starvation observed in AN. PMID:27271855

  14. Effects of maternal hypothyroidism during pregnancy on learning, memory and hippocampal BDNF in rat pups: Beneficial effects of exercise.

    Science.gov (United States)

    Shafiee, Seyed Morteza; Vafaei, Abbas Ali; Rashidy-Pour, Ali

    2016-08-01

    Hypothyroidism during early development leads to numerous morphological, biochemical and functional changes in developing brain. In this study, we investigated the effects of voluntary and treadmill exercise on learning, memory and hippocampal BDNF levels in both hypothyroid male and female rat pups. To induce hypothyroidism in the mothers, 6-propyl-2-thiouracil (PTU) was added to their drinking water (100mg/L) from their embryonic day 6 to their postnatal day (PND) 21. For 14days, from PNDs 31 to 44, the rat pups were trained with one of the two different exercise protocols, namely the mild treadmill exercise and the voluntary wheel exercise. On PNDs 45-52, a water maze was used for testing their learning and memory ability. The rats were sacrificed one day later and their BDNF levels were then measured in the hippocampus. The findings of the present study indicate that hypothyroidism during the fetal period and the early postnatal period is associated with the impairment of spatial learning and memory and reduced hippocampal BDNF levels in both male and female rat offspring. Both the short-term treadmill exercise and the voluntary wheel exercise performed during the postnatal period reverse the behavioral and neurochemical deficits induced by developmental thyroid hormone insufficiency in both male and female rat offspring. The findings of this study thus demonstrate a marked reversibility of both behavioral and neurochemical disorders induced by developmental thyroid hormone insufficiency through the performance of exercise. PMID:27181637

  15. Effects of the BDNF Val66Met Polymorphism on Gray Matter Volume in Typically Developing Children and Adolescents.

    Science.gov (United States)

    Hashimoto, Teruo; Fukui, Kento; Takeuchi, Hikaru; Yokota, Susumu; Kikuchi, Yoshie; Tomita, Hiroaki; Taki, Yasuyuki; Kawashima, Ryuta

    2016-04-01

    The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) is associated with psychiatric disorders and regional gray matter volume (rGMV) in adults. However, the relationship between BDNF and rGMV in children has not been clarified. In this 3-year cross-sectional/longitudinal (2 time points) study, we investigated the effects of BDNF genotypes on rGMV in 185 healthy Japanese children aged 5.7-18.4 using magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analyses. We found that the volume of the right cuneus in Met homozygotes (Met/Met) was greater than in Val homozygotes (Val/Val) in both exams, and the left insula and left ventromedial prefrontal cortex volumes were greater in Val homozygotes versus Met homozygotes in Exam l. In addition, Met homozygous subjects exhibited higher processing speed in intelligence indices than Val homozygotes and Val/Met heterozygotes at both time points. Longitudinal analysis showed that the left temporoparietal junction volume of Val/Met heterozygotes increased more substantially over the 3-year study period than in Val homozygotes, and age-related changes were observed for the Val/Met genotype. Our findings suggest that the presence of 2 Met alleles may have a positive effect on rGMV at the developmental stages analyzed in this study. PMID:26830347

  16. Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology.

    Science.gov (United States)

    Liu, Gele; Rustom, Nazneen; Litteljohn, Darcy; Bobyn, Jessica; Rudyk, Chris; Anisman, Hymie; Hayley, Shawn

    2014-01-01

    Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced pluripotent stem cells (iPSCs), and then subsequently transformed these cells into neural cells which over-expressed brain derived neurotrophic factor (BDNF). Importantly, the infusion of iPSC derived neural cells (as a cell replacement and gene delivery tool) and BDNF (as a protective factor) influenced neuronal outcomes. Specifically, intracerebroventricular transplantation of iPSC-derived neural progenitors that over-expressed BDNF reversed the impact of immune (lipopolysaccharide) and chronic stressor challenges upon subventricular zone adult neurogenesis, and the iPSC-derived neural progenitor cells alone blunted the stressor-induced corticosterone response. Moreover, our findings indicate that mature dopamine producing neurons can be generated using iPSC procedures and appear to be viable when infused in vivo. Taken together, these data could have important implications for using gene-plus-cell replacement methods to modulate stressor related pathology. PMID:25352778

  17. Use of induced pluripotent stem cell derived neurons engineered to express BDNF for modulation of stressor related pathology.

    Directory of Open Access Journals (Sweden)

    Hymie Anisman

    2014-10-01

    Full Text Available Combined cell and gene-based therapeutic strategies offer potential in the treatment of neurodegenerative and psychiatric conditions that have been associated with structural brain disturbances. In the present investigation, we used a novel virus-free re-programming method to generate induced pluripotent stem cells (iPSCs, and then subsequently transformed these cells into neural cells which over-expressed brain derived neurotrophic factor (BDNF. Importantly, the infusion of iPSC derived neural cells (as a cell replacement and gene delivery tool and BDNF (as a protective factor influenced neuronal outcomes Specifically, intracerebroventricular transplantation of iPSC-derived neural progenitors that over-expressed BDNF reversed the impact of immune (lipopolysaccharide and chronic stressor challenges upon subventricular zone adult neurogenesis and the iPSC-derived neural progenitor cells alone blunted the stressor induced corticosterone response. Moreover, our findings also indicate that mature dopamine producing neurons can also be generated using iPSC procedures and these cells appeared to be viable when infused in vivo. Taken together, these data could have important implications for using gene-plus-cell replacement methods to modulate stressor related pathology.

  18. Effect of 8 weeks Resistance Training on BDNF and TrkB in the Hippocampus of Adult Male Rats

    Directory of Open Access Journals (Sweden)

    S Mojtahedi

    2014-08-01

    Full Text Available Background & aim: Exercise enhances the synaptic plasticity and neuroprotective effects in the adult brain. However, it remains unknown that how plasticity molecules change following types of training. The purpose of this study was to determine the effect of eight weeks resistance training on protein levels of Brain Derived Neurotrophic Factor(BDNF and receptor of TrkB, in the hippocampus of adult male rats. Methods: In this experimental study, twelve adult male rats, 8 weeks of age, with an average weight of 200 to 225 grams were randomly divided into two groups, control and exercise respectively. The exercise was to increase the weight on the ladder. 24 hours after their last training session. The animals were killed and the hippocampus was removed for further testing. ELISA determined changes in protein levels. Data were analyzed by independent t test. Results: There was a significant difference between train and control groups In protein level of variables statically (p≤0.05. In addition, protein levels of BDNF and TrkB in the hippocampus of rats increased. Conclusion: Resistance training is beneficial for promoting hippocampal plasticity associated with BDNF signaling and consequently functional and cognitive benefits.

  19. The BDNF Val66Met polymorphism predicts rumination and depression differently in young adolescent girls and their mothers.

    Science.gov (United States)

    Hilt, Lori M; Sander, Lisa C; Nolen-Hoeksema, Susan; Simen, Arthur A

    2007-12-11

    A single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene Val66Met has been associated with depression. However, the relationship between this SNP and depression has been mixed, especially when comparing studies of child and adult depression. We examined whether Val66Met would predict depression differentially in mothers versus their daughters. We also examined whether rumination, the tendency to brood and repetitively think about negative information, might serve as a mediator in the path between genotype and depressive symptoms. Participants included 200 individuals (100 mother-daughter pairs) from a high-risk population. The BDNF Val66Met polymorphism was examined in DNA samples from the mothers and daughters, and measures of depressive symptoms and rumination were also obtained. Among the young adolescent girls (ages 10-14), the Val/Val genotype was associated with more depressive symptoms and higher rumination scores compared to the Val/Met genotype. Furthermore, rumination mediated the relationship between genotype and depressive symptoms. However, in the mothers with adult-onset depression the Val/Met genotype was associated with more depressive symptoms, and rumination again mediated the relationship between genotype and depression. Rumination may be an endophenotype in the pathway from the BDNF Val66Met polymorphism to depression. Future work should further explore this mechanism and pursue explanations for its effects at different times in development. PMID:17959306

  20. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF

    Science.gov (United States)

    Hurley, Laura L.; Akinfiresoye, Luli; Nwulia, Evaristus; Kamiya, Atsushi; Kulkarni, Amol; Tizabi, Yousef

    2012-01-01

    Curcumin is the principal active ingredient found in turmeric (Curcuma longa), a plant used in traditional Asian diets and herbal medicines. It is known to have a wide range of biological actions including antidepressant-like effects which have been observed in stress-induced depression models. This study was designed to investigate the antidepressant potential of curcumin in a non-induced model of depression. Moreover, since brain derived neurotrophic factor (BDNF) has been implicated in antidepressant effects of many drugs, we also evaluated the effects of curcumin on BDNF in the hippocampus. Adult male Wistar Kyoto (WKY) rats, a putative model of depression, were injected acutely or chronically (10 d) with 50, 100, and 200mg/kg curcumin. Open field locomotor activity (OFLA) and forced swim test (FST), a measure of helplessness, were measured 1 hour after acute and 18–20 hours after last chronic injection. Results showed a dose-dependent reduction of immobility in the FST by curcumin in both acute and chronic studies, without any significant effect on OFLA. The effect of higher chronic curcumin dose in FST was still evident a week later. Chronic curcumin also resulted in a dose-dependent increase in hippocampal BDNF. This data provides evidence for an antidepressant-like effect of curcumin, possibly through increased neurotrophic activity, in the WKY model of depression, and support the notion that curcumin may prove an effective and lasting natural antidepressant. PMID:23142609

  1. Higher reward value of starvation imagery in anorexia nervosa and association with the Val66Met BDNF polymorphism

    Science.gov (United States)

    Clarke, J; Ramoz, N; Fladung, A-K; Gorwood, P

    2016-01-01

    Recent studies support the idea that abnormalities of the reward system contribute to onset and maintenance of anorexia nervosa (AN). Next to cues coding for overweight, other research suggest cues triggering the proposed starvation dependence to be pivotally involved in the AN pathogenesis. We assessed the characteristics of the cognitive, emotional and physiologic response toward disease-specific pictures of female body shapes, in adult AN patients compared with healthy control (HC) women. Frequency and amplitude of skin conductance response (SCR) in 71 patients with AN and 20 HC were registered during processing of stimuli of three weight categories (over-, under- and normal weight). We then assessed the role of the Val66Met BDNF polymorphism as a potential intermediate factor. AN patients reported more positive feelings during processing of underweight stimuli and more negative feelings for normal- and overweight stimuli. The SCR showed a group effect (P=0.007), AN patients showing overall higher frequency of the response. SCR within patients was more frequent during processing of underweight stimuli compared with normal- and overweight stimuli. The Met allele of the BDNF gene was not more frequent in patients compared with controls, but was associated to an increased frequency of SCR (P=0.008) in response to cues for starvation. A higher positive value of starvation, rather than more negative one of overweight, might more accurately define females with AN. The Met allele of the BDNF gene could partly mediate the higher reward value of starvation observed in AN. PMID:27271855

  2. Environmental and Genetic Activation of Hypothalamic BDNF Modulates T-cell Immunity to Exert an Anticancer Phenotype.

    Science.gov (United States)

    Xiao, Run; Bergin, Stephen M; Huang, Wei; Slater, Andrew M; Liu, Xianglan; Judd, Ryan T; Lin, En-Ju D; Widstrom, Kyle J; Scoville, Steven D; Yu, Jianhua; Caligiuri, Michael A; Cao, Lei

    2016-06-01

    Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) providing complex stimuli confers an anticancer phenotype in mice mediated, in part by a specific neuroendocrine axis, with brain-derived neurotrophic factor (BDNF) as the key brain mediator. Here, we investigated how an EE modulated T-cell immunity and its role in the EE-induced anticancer effects. Our data demonstrated that CD8 T cells were required to mediate the anticancer effects of an EE in an orthotropic model of melanoma. In secondary lymphoid tissue (SLT), an EE induced early changes in the phenotype of T-cell populations, characterized by a decrease in the ratio of CD4 T helper to CD8 cytotoxic T lymphocytes (CTL). Overexpression of hypothalamic BDNF reproduced EE-induced T-cell phenotypes in SLT, whereas knockdown of hypothalamic BDNF inhibited EE-induced immune modulation in SLT. Both propranolol and mifepristone blocked the EE-associated modulation of CTLs in SLT, suggesting that both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis were involved. Our results demonstrated that enhanced anticancer effect of an EE was mediated at least in part through modulation of T-cell immunity and provided support to the emerging concept of manipulating a single gene in the brain to improve cancer immunotherapy. Cancer Immunol Res; 4(6); 488-97. ©2016 AACR. PMID:27045020

  3. Lactoferrin Promotes Early Neurodevelopment and Cognition in Postnatal Piglets by Upregulating the BDNF Signaling Pathway and Polysialylation.

    Science.gov (United States)

    Chen, Yue; Zheng, Zhiqiang; Zhu, Xi; Shi, Yujie; Tian, Dandan; Zhao, Fengjuan; Liu, Ni; Hüppi, Petra S; Troy, Frederic A; Wang, Bing

    2015-08-01

    Lactoferrin (Lf) is a sialic acid (Sia)-rich, iron-binding milk glycoprotein that has multifunctional health benefits. Its potential role in neurodevelopment and cognition remains unknown. To test the hypothesis that Lf may function to improve neurodevelopment and cognition, the diet of postnatal piglets was supplemented with Lf from days 3 to 38. Expression levels of selected genes and their cognate protein profiles were quantitatively determined. The importance of our new findings is that Lf (1) upregulated several canonical signaling pathways associated with neurodevelopment and cognition; (2) influenced ~10 genes involved in the brain-derived neurotrophin factor (BDNF) signaling pathway in the hippocampus and upregulated the expression of polysialic acid, a marker of neuroplasticity, cell migration and differentiation of progenitor cells, and the growth and targeting of axons; (3) upregulated transcriptional and translational levels of BDNF and increased phosphorylation of the cyclic adenosine monophosphate (cAMP) response element-binding protein, CREB, a downstream target of the BDNF signaling pathway, and a protein of crucial importance in neurodevelopment and cognition; and (4) enhanced the cognitive function and learning of piglets when tested in an eight-arm radial maze. The finding that Lf can improve neural development and cognition in postnatal piglets has not been previously described. PMID:25146846

  4. Electronic structure of point defects in semiconductors

    International Nuclear Information System (INIS)

    This 'Habilitation a diriger des Recherches' memoir presents most of my scientific activities during the past 7 years, in the field of electronic structure calculations of defects in solids. Point defects (vacancies, interstitials, impurities) in functional materials are a key parameter to determine if these materials will actually fill the role they have been assigned or not. Indeed, the presence of defects cannot be avoided when the temperature is increased or when the material is subjected to external stresses, such as irradiation in the nuclear reactors and in artificial satellites with solar radiations. However, in many cases, defects are introduced in the materials on purpose to tune the electronic transport, optical or even magnetic properties. This procedure is called the doping of semiconductors, which is the foundation technique for transistors, diodes, or photovoltaic cells. However, doping is not always straightforward and unexpected features may occur, such as doping asymmetry or Fermi level pinning, which can only be explained by complex phenomena involving different types of defects or complexes of defects. In this context, the calculations of electronic structure ab initio is an ideal tool to complement the experimental observations, to gain the understanding of phenomena at the atomic level, and even to predict the properties of defects. The power of the ab initio calculations comes from their ability to describe any system of electrons and nuclei without any specific adjustment. But although there is a strong need for numerical simulations in this field, the ab initio calculations for defects are still under development as of today. The work presented in this memoir summarizes my contributions to methodological developments on this subject. These developments have followed two main tracks. The first topic is the better understanding of the unavoidable finite size effects. Indeed, defects in semiconductors or insulators are generally present in

  5. Serum brain-derived neurotrophic factor (BDNF) levels in patients with panic disorder: as a biological predictor of response to group cognitive behavioral therapy.

    Science.gov (United States)

    Kobayashi, Keisuke; Shimizu, Eiji; Hashimoto, Kenji; Mitsumori, Makoto; Koike, Kaori; Okamura, Naoe; Koizumi, Hiroki; Ohgake, Shintaro; Matsuzawa, Daisuke; Zhang, Lin; Nakazato, Michiko; Iyo, Masaomi

    2005-06-01

    Little is known about biological predictors of treatment response in panic disorder. Our previous studies show that the brain-derived neurotrophic factor (BDNF) may play a role in the pathophysiology of major depressive disorders and eating disorders. Assuming that BDNF may be implicated in the putative common etiologies of depression and anxiety, the authors examined serum BDNF levels of the patients with panic disorder, and its correlation with therapeutic response to group cognitive behavioral therapy (CBT). Group CBT (10 consecutive 1 h weekly sessions) was administered to the patients with panic disorder after consulting the panic outpatient special service. Before treatment, serum concentrations of BDNF and total cholesterol were measured. After treatment, we defined response to therapy as a 40% reduction from baseline on Panic Disorder Severity Scale (PDSS) score as described by [Barlow, D.H., Gorman, J.M., Shear, M.K., Woods, S.W., 2000. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. JAMA. 283, 2529-2536]. There were 26 good responders and 16 poor responders. 31 age- and sex-matched healthy normal control subjects were also recruited in this study. The serum BDNF levels of the patients with poor response (25.9 ng/ml [S.D. 8.7]) were significantly lower than those of the patients with good response (33.7 ng/ml [S.D. 7.5]). However, there were no significant differences in both groups of the patients, compared to the normal controls (29.1 ng/ml [S.D. 7.1]). No significant differences of other variables including total cholesterol levels before treatment were detected between good responders and poor responders. These results suggested that BDNF might contribute to therapeutic response of panic disorder. A potential link between an increased risk of secondary depression and BDNF remains to be investigated in the future. PMID:15905010

  6. Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain--a resting-state fMRI pilot study.

    Science.gov (United States)

    Mueller, Karsten; Arelin, Katrin; Möller, Harald E; Sacher, Julia; Kratzsch, Jürgen; Luck, Tobias; Riedel-Heller, Steffi; Villringer, Arno; Schroeter, Matthias L

    2016-02-01

    Brain-derived neurotrophic factor (BDNF) has been discussed to be involved in plasticity processes in the human brain, in particular during aging. Recently, aging and its (neurodegenerative) diseases have increasingly been conceptualized as disconnection syndromes. Here, connectivity changes in neural networks (the connectome) are suggested to be the most relevant and characteristic features for such processes or diseases. To further elucidate the impact of aging on neural networks, we investigated the interaction between plasticity processes, brain connectivity, and healthy aging by measuring levels of serum BDNF and resting-state fMRI data in 25 young (mean age 24.8 ± 2.7 (SD) years) and 23 old healthy participants (mean age, 68.6 ± 4.1 years). To identify neural hubs most essentially related to serum BDNF, we applied graph theory approaches, namely the new data-driven and parameter-free approach eigenvector centrality (EC) mapping. The analysis revealed a positive correlation between serum BDNF and EC in the premotor and motor cortex in older participants in contrast to young volunteers, where we did not detect any association. This positive relationship between serum BDNF and EC appears to be specific for older adults. Our results might indicate that the amount of physical activity and learning capacities, leading to higher BDNF levels, increases brain connectivity in (pre)motor areas in healthy aging in agreement with rodent animal studies. Pilot results have to be replicated in a larger sample including behavioral data to disentangle the cause for the relationship between BDNF levels and connectivity. PMID:26827656

  7. Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence

    International Nuclear Information System (INIS)

    Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions

  8. Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence

    Energy Technology Data Exchange (ETDEWEB)

    Xu, R.; Duan, S.R.; Zhao, J.W.; Wang, C.Y. [Neurology Ward of Internal Medicine, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province (China)

    2015-06-23

    Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.

  9. Birth Defects. Matrix No. 2.

    Science.gov (United States)

    Brent, Robert L.

    This report discusses the magnitude of the problem of birth defects, outlines advances in the birth defects field in the past decade, and identifies those areas where research is needed for the prevention, treatment, and management of birth defects. The problem of birth defects has consumed a greater portion of our health care resources because of…

  10. Defect Management Strategies in Software Development

    OpenAIRE

    V, Suma; T.R., Gopalakrishnan Nair

    2012-01-01

    Software is a unique entity that has laid a strong impact on all other fields either related or not related to software. These include medical, scientific, business, educational, defence, transport, telecommunication to name a few. State-of-the-art professional domain activities demands the development of high quality software. High quality software attributes to a defect-free product, which is competent of producing predictable results and remains deliverable within time and cost constraints...

  11. Trophic mechanisms for exercise-induced stress resilience: Potential role of interactions between BDNF and galanin

    Directory of Open Access Journals (Sweden)

    Philip V Holmes

    2014-07-01

    Full Text Available Current concepts of the neurobiology of stress-related disorders such as anxiety and depression emphasize disruptions in neural plasticity and neurotrophins. The potent trophic actions of exercise therefore represent not only an effective means for prevention and treatment of these disorders, they also afford the opportunity to employ exercise paradigms as a basic research tool to uncover the neurobiological mechanisms underlying these disorders. Novel approaches to studying stress-related disorders focus increasingly on trophic factor signaling in corticolimbic circuits that both mediate and regulate cognitive, behavioral, and physiological responses to deleterious stress. Recent evidence demonstrates that the neural plasticity supported by these trophic mechanisms is vital for establishing and maintaining resilience to stress. Therapeutic interventions that promote these mechanisms, be they pharmacological, behavioral, or environmental, may therefore prevent or reverse stress-related mental illness by enhancing resilience. The present paper will provide an overview of trophic mechanisms responsible for the enhancement of resilience by voluntary exercise with an emphasis on BDNF, galanin, and interactions between these two trophic factors.

  12. Antidepressant Effects of AMPA and Ketamine Combination: Role of Hippocampal BDNF, Synapsin, and mTOR

    Science.gov (United States)

    Akinfiresoye, Luli; Tizabi, Yousef

    2013-01-01

    Rationale A number of preclinical and clinical studies suggest ketamine, a glutamate NMDA (N-methyl-D-aspartate) receptor antagonist, has a rapid and lasting antidepressant effect when administered either acutely or chronically. It has been postulated that this effect is due to stimulation of AMPA (alpha-amino-3-hydroxy-5-methyl–4-isoxazolepropionic acid) receptors. Objective In this study, we tested whether AMPA alone has an antidepressant effect and if the combination of AMPA and ketamine provides added benefit in Wistar-Kyoto (WKY) rats, a putative animal model of depression. Results Chronic AMPA treatment resulted in a dose dependent antidepressant effect in both the forced swim test (FST) and sucrose preference test. Moreover, chronic administration (10–11d) of combinations of AMPA and ketamine, at doses that were ineffective on their own, resulted in a significant antidepressant effect. The behavioral effects were associated with increases in hippocampal brain derived neurotrophic factor (BDNF), synapsin, and mammalian target of rapamycin (mTOR). Conclusion These findings are the first to provide evidence for an antidepressant effect of AMPA, and suggest the usefulness of AMPA-ketamine combination in treatment of depression. Furthermore, these effects appear to be associated with increases in markers of hippocampal neurogenesis and synaptogenesis, suggesting a mechanism of their action. PMID:23732839

  13. Physical exercise neuroprotects ovariectomized 3xTg-AD mice through BDNF mechanisms.

    Science.gov (United States)

    García-Mesa, Yoelvis; Pareja-Galeano, Helios; Bonet-Costa, Vicent; Revilla, Susana; Gómez-Cabrera, M Carmen; Gambini, Juan; Giménez-Llort, Lydia; Cristòfol, Rosa; Viña, José; Sanfeliu, Coral

    2014-07-01

    Postmenopausal women may be more vulnerable to cognitive loss and Alzheimer's disease (AD) than premenopausal women because of their deficiency in estrogens, in addition to their usually older age. Aerobic physical exercise has been proposed as a therapeutic approach for maintaining health and well-being in postmenopausal women, and for improving brain health and plasticity in populations at high risk for AD. To study the neuroprotective mechanisms of physical exercise in a postmenopausal animal model, we submitted previously ovariectomized, six-month old non-transgenic and 3xTg-AD mice to three months of voluntary exercise in a running wheel. At nine months of age, we observed lower grip strength and some exacerbation of the behavioral and psychological symptoms of dementia (BPSD)-like involving active exploratory activities. A similar major cognitive impairment was observed of ovariectomized 3xTg-AD mice in comparison with sham-operated 3xTg-AD mice. A reduction of bodily fitness and lack of retention of memory were observed in the ovariectomized non-transgenic mice. Physical exercise protected against all deleterious behaviors and normalized learning and memory. It also protected against body frailty, as expected. Analyses of hippocampal key markers of antioxidant and neuroplasticity signaling pathways, showed that ovariectomy impairs the activation of CREB through physical exercise. Furthermore, molecular and behavioral correlates suggested a central role of BDNF in the neuroprotection mediated by physical exercise therapy against apathy and memory loss induced by ovariectomy and the AD-genotype. PMID:24845186

  14. DEFECTS SIMULATION OF ROLLING STRIP

    OpenAIRE

    Rudolf Mišičko; Tibor Kvačkaj; Martin Vlado; Lucia Gulová; Miloslav Lupták; Jana Bidulská

    2009-01-01

    The defects in the continuous casting slabs can be developed or kept down in principle by rolling technology, especially depend to sort, size and distribution of primary defects, as well as used of rolling parameters. Scope of the article is on observation behavior artificial surface and undersurface defects (scores) without filler (surface defects) and filling by oxides and casting powder (subsurface defects). First phase of hot rolling process have been done by software simulation DEFORM 3D...

  15. Supersymmetric k-defects

    Science.gov (United States)

    Koehn, Michael; Trodden, Mark

    2016-04-01

    In supersymmetric theories, topological defects can have nontrivial behaviors determined purely by whether or not supersymmetry is restored in the defect core. A well-known example of this is that some supersymmetric cosmic strings are automatically superconducting, leading to important cosmological effects and constraints. We investigate the impact of nontrivial kinetic interactions, present in a number of particle physics models of interest in cosmology, on the relationship between supersymmetry and supercurrents on strings. We find that in some cases it is possible for superconductivity to be disrupted by the extra interactions.

  16. 宫内移植rAAV-BDNF对抑制胚胎期显性脊柱裂胎鼠神经细胞凋亡的影响%Study on uterine transplantation of rAAV-BDNF to control nerve cell apoptosis of rat fetuses with spina bifida aperta

    Institute of Scientific and Technical Information of China (English)

    田聪亮; 李慧; 赵桂锋; 刘波; 苗佳宁; 曹嵩颖; 袁正伟

    2013-01-01

    .The expression of BDNF in the treatment group was significantly increased compared with the empty vector treatment and control groups.TUNEL staining showed that the average number of apoptotic cells in each spinal cord slice in the treatment group was significantly decreased compared with the empty vector treatment and control groups.Conclusions The use of genetically-modified therapy to inject rAAV-BDNF into congenital spinal bifida fetal rat spinal cord defects significantly inhibited neuronal apoptosis,which has potential application to treat dominant spina bifida.

  17. Learning abilities, NGF and BDNF brain levels in two lines of TNF-alpha transgenic mice, one characterized by neurological disorders, the other phenotypically normal.

    Science.gov (United States)

    Aloe, L; Properzi, F; Probert, L; Akassoglou, K; Kassiotis, G; Micera, A; Fiore, M

    1999-09-01

    In this study we used two lines of transgenic mice overexpressing tumor necrosis factor alpha (TNF-alpha) in the central nervous system (CNS), one characterized by reactive gliosis, inflammatory demyelination and neurological deficits (Tg6074) the other showing no neurological or phenotypical alterations (TgK3) to investigate the effect of TNF-alpha on brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels and learning abilities. The results showed that the amount of NGF in the brain of Tg6074 and TgK3 transgenic mice is low in the hippocampus and in the spinal cord, increases in the hypothalamus of Tg6074 and showed no significant changes in the cortex. BDNF levels were low in the hippocampus and spinal cord of TgK3. BDNF increased in the hypothalamus of TgK3 and Tg6074 while in the cortex, BDNF increased only in Tg6074 mice. Transgenic mice also had memory impairments as revealed by the Morris Water Maze test. These findings indicate that TNF-alpha significantly influences BDNF and NGF synthesis, most probably in a dose-dependent manner. Learning abilities were also differently affected by overexpression of TNF-alpha, but were not associated with inflammatory activity. The possible functional implications of our findings are discussed. PMID:10517960

  18. Reduced Hippocampal Dendritic Spine Density and BDNF Expression following Acute Postnatal Exposure to Di(2-Ethylhexyl) Phthalate in Male Long Evans Rats

    Science.gov (United States)

    Smith, Catherine A.; Holahan, Matthew R.

    2014-01-01

    Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats. PMID:25295592

  19. Diurnal pattern of serum BDNF before partial sleep deprivation in stress-related mood disorders – an association with therapy response in major depression

    Directory of Open Access Journals (Sweden)

    Maria Giese

    2012-09-01

    Full Text Available Background : Depression is one of the most prevalent forms of mood disorders. Compelling evidence suggests that mood disorders are characterized by reduced neuronal plasticity, which can be brought about by exposure to stress. Furthermore, there is good agreement in considering key proteins such as the brain-derived neurotrophic factor (BDNF, as a central player for the effects of stress on brain function and plasticity and psychopathological implications. Still, there is a high non-responder rate in antidepressant therapy, which explains the need to find reliable predictors for adequate treatment. Previous studies revealed that plasma and serum BDNF levels in depressed patients were significantly lower than in healthy controls. Since the protein can cross the blood brain-barrier serum content correspondingly correlates with cortical BDNF concentrations suggesting BDNF levels as a promising candidate biomarker for depression and antidepressant treatment response. Methods : To investigate the association between serum BDNF levels and treatment outcome, blood was drawn from 28 patients with a major depressive episode (DMS-IV, ICD-10 that participated in a double-blind placebo controlled treatment study. All patients were treated with a stable mirtazapine monotherapy. Partial sleep deprivation (PSD was performed after one week. Placebo controlled additional morning treatment with the stimulant modafinil to reduce microsleep throughout the day was started during PSD and maintained over two weeks. Serum concentrations of BDNF and cortisol were assessed by an enzyme-linked immunosorbent assay (ELISA from day 1 (“before PSD” at 8 am, 2 pm, 8 pm and day 2 (“after PSD” at 8 am, 2 pm and 8 pm. Samples were appropriately diluted and detection of soluble BDNF or cortisol was carried out in an antibody sandwich format in duplicates and means were calculated for the corresponding group. Moreover, sleep EEG and microsleep episodes were

  20. Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.

    Science.gov (United States)

    Gomar, Jesus J; Conejero-Goldberg, Concepcion; Huey, Edward D; Davies, Peter; Goldberg, Terry E

    2016-03-01

    Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging. PMID:26923413

  1. Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression.

    Science.gov (United States)

    de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; Vasconcelos, Germana Silva; Silva, Márcia Calheiros Chaves; da Silva, Jéssica Calheiros; Macêdo, Danielle; de Lucena, David Freitas; Vasconcelos, Silvânia Maria Mendes

    2015-12-15

    Brain derived neurotrophic factor (BDNF) is linked to the pathophysiology of depression. We hypothesized that BDNF is one of the neurobiological pathways related to the augmentation effect of alpha-lipoic acid (ALA) when associated with antidepressants. Female mice were administered vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days the animals were divided in groups that were further administered: vehicle, desvenlafaxine (DVS) 10 or 20mg/kg, ALA 100 or 200mg/kg or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200 or DVS20+ALA200. ALA or DVS alone or in combination reversed CORT-induced increase in immobility time in the forced swimming test and decrease in sucrose preference, presenting, thus, an antidepressant-like effect. DVS10 alone reversed CORT-induced decrease in BDNF in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The same was observed in the HC and ST of ALA200 treated animals. The combination of DVS and ALA200 reversed CORT-induced alterations in BDNF and even, in some cases, increased the levels of this neurotrophin when compared to vehicle-treated animals in HC and ST. Taken together, these results suggest that the combination of the DVS+ALA may be valuable for treating conditions in which BDNF levels are decreased, such as depression. PMID:26350703

  2. Production of point defects

    International Nuclear Information System (INIS)

    Vacancies at thermodynamic equilibrium and the annealing of these defects are studied first, after which electron irradiations are dealt with. The displacement threshold energy concept is introduced. Part three concerns heavy ion and neutron irradiations. Displacement cascades and the thermal spike concept are discussed

  3. Quantum computing with defects.

    Science.gov (United States)

    Weber, J R; Koehl, W F; Varley, J B; Janotti, A; Buckley, B B; Van de Walle, C G; Awschalom, D D

    2010-05-11

    Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV(-1)) center stands out for its robustness--its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar quantum-mechanical properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate defect systems. To illustrate these points in detail, we compare electronic structure calculations of the NV(-1) center in diamond with those of several deep centers in 4H silicon carbide (SiC). We then discuss the proposed criteria for similar defects in other tetrahedrally coordinated semiconductors. PMID:20404195

  4. Topological defects in CFT

    Energy Technology Data Exchange (ETDEWEB)

    Petkova, V. B., E-mail: petkova@inrne.bas.bg [Bulgarian Academy of Sciences, Institute of Nuclear Research and Nuclear Energy (Bulgaria)

    2013-10-15

    Areview of the notion, properties and the use of topological defects in 2d conformal field theories is presented. An emphasis is made on the recent interpretation of such operators in non-rational theories, as describing Wilson-'t Hooft loop operators of N = 2 supersymmetric 4d topological theories.

  5. Effect of topological defects on "nuclear pasta" observables

    CERN Document Server

    Schneider, A S; Caplan, M E; Horowitz, C J; Lin, Z

    2016-01-01

    [Background] The "pasta" phase of nuclear matter may play an important role in the structure and evolution of neutron stars. Recent works suggest nuclear pasta has a high resistivity which could be explained by the presence of long lived topological defects. The defects act as impurities that decrease thermal and electrical conductivity of the pasta. [Purpose] To quantify how topological defects affect transport properties of nuclear pasta and estimate this effect using an impurity parameter $Q_{\\text{imp}}$. [Methods] Contrast molecular dynamics simulations of up to 409\\,600 nucleons arranged in parallel nuclear pasta slabs (perfect pasta) with simulations of pasta slabs connected by topological defects (impure pasta). From these simulations compare the viscosity and heat conductivity of perfect and impure pasta to obtain an effective impurity parameter $Q_{\\text{imp}}$ due to the presence of defects. [Results] Both the viscosity and thermal conductivity calculated for both perfect and impure pasta are aniso...

  6. Point Defect Characterization in CdZnTe

    Energy Technology Data Exchange (ETDEWEB)

    Gul,R.; Li, Z.; Bolotnikov, A.; Keeter, K.; Rodriguez, R.; James, R.

    2009-03-24

    Measurements of the defect levels and performance testing of CdZnTe detectors were performed by means of Current Deep Level Transient Spectroscopy (I-DLTS), Transient Charge Technique (TCT), Current versus Voltage measurements (I-V), and gamma-ray spectroscopy. CdZnTe crystals were acquired from different commercial vendors and characterized for their point defects. I-DLTS studies included measurements of defect parameters such as energy levels in the band gap, carrier capture cross sections, and defect densities. The induced current due to laser-generated carriers was measured using TCT. The data were used to determine the transport properties of the detectors under study. A good correlation was found between the point defects in the detectors and their performance.

  7. Graphene materials having randomly distributed two-dimensional structural defects

    Science.gov (United States)

    Kung, Harold H; Zhao, Xin; Hayner, Cary M; Kung, Mayfair C

    2013-10-08

    Graphene-based storage materials for high-power battery applications are provided. The storage materials are composed of vertical stacks of graphene sheets and have reduced resistance for Li ion transport. This reduced resistance is achieved by incorporating a random distribution of structural defects into the stacked graphene sheets, whereby the structural defects facilitate the diffusion of Li ions into the interior of the storage materials.

  8. Graphene materials having randomly distributed two-dimensional structural defects

    Energy Technology Data Exchange (ETDEWEB)

    Kung, Harold H.; Zhao, Xin; Hayner, Cary M.; Kung, Mayfair C.

    2016-05-31

    Graphene-based storage materials for high-power battery applications are provided. The storage materials are composed of vertical stacks of graphene sheets and have reduced resistance for Li ion transport. This reduced resistance is achieved by incorporating a random distribution of structural defects into the stacked graphene sheets, whereby the structural defects facilitate the diffusion of Li ions into the interior of the storage materials.

  9. Defect identification by compositional defect review using auger electron spectroscopy

    International Nuclear Information System (INIS)

    Defect identification plays an enabling role in determining the source of particles that occur during semiconductor processing and are subsequently detected by defect inspection tools. Auger electron spectroscopy provides a high spatial resolution, surface sensitive analytical probe that is well matched to examining small, thin or complex defects. A focused ion beam (FIB) can be used to cross-section buried defects and structures for subsequent Auger analysis. Such measurements have been made on defects from two wafers pulled at different process steps. One wafer was analyzed after poly-Si deposition, and the other wafer was analyzed after metal 2 etch. The defects on the poly-Si wafer are Si particles. Three types of particles were found on the metal 2 wafer: C-based, stainless steel, and Si-oxide. The majority of defects on this wafer are C-based. Auger, EDS and FIB results will be compared for representative defects on these two wafers

  10. Conductivity of epitaxial and CVD graphene with correlated line defects

    DEFF Research Database (Denmark)

    Radchenko, T. M.; Shylau, Artsem; Zozoulenko, I. V.

    2014-01-01

    Transport properties of single-layer graphene with correlated one-dimensional defects are studied theoretically using the computational model within the time-dependent real-space Kubo-Greenwood formalism. Such defects are present in epitaxial graphene, comprising atomic terraces and steps due to...... the substrate morphology, and in polycrystalline chemically vapor-deposited (CVD) graphene due to the grain boundaries, composed of a periodic array of dislocations, or quasi-periodic nanoripples originated from the metal substrate. The extended line defects are described by the long-range Lorentzian...

  11. Multimarker analysis suggests the involvement of BDNF signaling and microRNA biosynthesis in suicidal behavior.

    Science.gov (United States)

    Pulay, Attila J; Réthelyi, János M

    2016-09-01

    Despite moderate heritability estimates the genetics of suicidal behavior remains unclear, genome-wide association and candidate gene studies focusing on single nucleotide associations reported inconsistent findings. Our study explored biologically informed, multimarker candidate gene associations with suicidal behavior in mood disorders. We analyzed the GAIN Whole Genome Association Study of Bipolar Disorder version 3 (n = 999, suicidal n = 358) and the GAIN Major Depression: Stage 1 Genomewide Association in Population-Based Samples (n = 1,753, suicidal n = 245) datasets. Suicidal behavior was defined as severe suicidal ideation or attempt. Candidate genes were selected based on literature search (Geneset1, n = 35), gene expression data of microRNA genes, (Geneset2, n = 68) and their target genes (Geneset3, n = 11,259). Quality control, dosage analyses were carried out with PLINK. Gene-based associations of Geneset1 were analyzed with KGG. Polygenic profile scores of suicidal behavior were computed in the major depression dataset both with PRSice and LDpred and validated in the bipolar disorder data. Several nominally significant gene-based associations were detected, but only DICER1 associated with suicidal behavior in both samples, while only the associations of NTRK2 in the depression sample reached family wise and experiment wise significance. Polygenic profile scores negatively predicted suicidal behavior in the bipolar sample for only Geneset2, with the strongest prediction by PRSice at Pt  < 0.03 (Nagelkerke R(2)  = 0.01, P < 0.007). Gene-based association results confirmed the potential involvement of the BDNF-NTRK2-CREB pathway in the pathogenesis of suicide and the cross-disorder association of DICER1. Polygenic risk prediction of the selected miRNA genes indicates that the miRNA system may play a mediating role, but with considerable pleiotropy. © 2016 Wiley Periodicals, Inc. PMID:26921221

  12. BDNF pathway is involved in the protective effects of SS-31 on isoflurane-induced cognitive deficits in aging mice.

    Science.gov (United States)

    Wu, Jing; Zhang, Mingqiang; Li, Huihui; Sun, Xiaoru; Hao, Shuangying; Ji, Muhuo; Yang, Jianjun; Li, Kuanyu

    2016-05-15

    Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation. Behavioral tests were evaluated by the open field test and fear conditioning test 24h after the experiment. We showed that cognitive deficits induced by exposure of the aging mice to isoflurane were accompanied by mitochondrial dysfunction in hippocampus due to loss of the enzymatic activity of complex I. This loss resulted in the increase of reactive oxygen species production, decrease of ATP production and mitochondrial membrane potential, and opening of mitochondrial permeability transition pore. Further, we provided evidence that the BDNF signaling pathway was involved in this process to regulate synaptic plasticity-related proteins, for instance, downregulation of synapsin 1, PSD-95 and p-CREB, and upregulation of NR2A, NR2B, CaMKIIα and CaMKIIβ. Of note, the isoflurane-induced cognitive deficits were rescued by SS-31 through reversal of mitochondrial dysfunction, which facilitated the regulation of BDNF signaling including the expression reversal of aforementioned important synaptic-signaling proteins in aging mice. Our data demonstrate that reversing mitochondrial dysfunction by SS-31 enhances BDNF signaling pathway and synaptic plasticity, and provides protective effects on cognitive function, thereby support the notion that SS-31 may have therapeutic benefits for elderly humans undertaking anesthesia. PMID:26944333

  13. Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus.

    Science.gov (United States)

    Zheng, Yu; Fan, Weidong; Zhang, Xianquan; Dong, Erbo

    2016-01-01

    Exposure to stressful life events during pregnancy exerts profound effects on neurodevelopment and increases the risk for several neurodevelopmental disorders including major depression. The mechanisms underlying the consequences of gestational stress are complex and remain to be elucidated. This study investigated the effects of gestational stress on depressive-like behavior and epigenetic modifications in young adult offspring. Gestational stress was induced by a combination of restraint and 24-hour light disturbance to pregnant dams throughout gestation. Depressive-like and anxiety-like behaviors of young adult offspring were examined. The expression and promoter methylation of brain derived neurotrophic factor (BDNF) were measured using RT-qPCR, Western blot, methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). In addition, the expressions of histone deacetylases (HDACs) and acetylated histone H3 lysine 14 (AcH3K14) were also analyzed. Our results show that offspring from gestational stress dams exhibited depressive-like and anxiety-like behaviors. Biochemically, stress-offspring showed decreased expression of BDNF, increased expression of DNMT1, HDAC1, and HDAC2, and decreased expression of AcH3K14 in the hippocampus as compared to non-stress offspring. Data from MeDIP and ChIP assays revealed an increased methylation as well as decreased binding of AcH3K14 on specific BDNF promoters. Pearson analyses indicated that epigenetic changes induced by gestational stress were correlated with depressive-like and anxiety-like behaviors. These data suggest that gestational stress may be a suitable model for understanding the behavioral and molecular epigenetic changes observed in patients with depression. PMID:26890656

  14. Comparison of efficacy, safety and brain derived neurotrophic factor (BDNF) levels in patients of major depressive disorder, treated with fluoxetine and desvenlafaxine.

    Science.gov (United States)

    Ghosh, R; Gupta, R; Bhatia, M S; Tripathi, A K; Gupta, L K

    2015-12-01

    This randomized, open label, prospective, observational study compared clinical efficacy, safety alongwith plasma BDNF levels in outpatients of depression treated with fluoxetine and desvenlafaxine. Patients (aged 18-60 years) with moderate to severe major depressive disorder (MDD) diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥14, who were prescribed fluoxetine or desvenlafaxine were included (n=30 in each group). Patients were followed up for 12 weeks for evaluation of clinical efficacy, safety along with BDNF levels. In the fluoxetine group, HAM-D scores at the start of treatment was 19±4.09 which significantly (p<0.05) reduced to 9.24±3.98 at 12 weeks. In the desvenlafaxine group, HAM-D scores at the start of treatment was 18±3.75 which significantly (p<0.05) reduced to 10±3.75 at 12 weeks. The BDNF levels in the fluoxetine group were 775.32±30.38pg/ml at the start of treatment which significantly (p<0.05) increased to 850.3±24.92pg/ml at 12 weeks. The BDNF levels in the desvenlafaxine group were 760.5±28.53pg/ml at the start of treatment which significantly (p<0.05) increased to 845.8±32.82pg/ml at 12 weeks. Both the antidepressants were found to be safe and well tolerated. The efficacy and the safety profile of desvenlafaxine is comparable to fluoxetine in patients of MDD. BDNF levels were significantly increased post-treatment with both the antidepressive agents. Whether BDNF may have a prognostic value in predicting treatment response to antidepressant drugs needs to be investigated in a larger patient population. PMID:26514447

  15. Birth Defects Research and Tracking

    Science.gov (United States)

    ... Podcasts & Video E-Cards Flu Badge Real Stories Cleft Lip and Palate Craniosynostosis Down Syndrome Eye Defects Fetal Alcohol Syndrome ... premature birth, certain birth defects (such as cleft lip, cleft palate, or both ), and infant death. Quitting smoking before ...

  16. Impact of Congenital Heart Defects

    Science.gov (United States)

    ... High Blood Pressure Tools & Resources Stroke More The Impact of Congenital Heart Defects Updated:Oct 21,2015 ... is an important part of successful coping. The Impact of Congenital Heart Defects • Home • About Congenital Heart ...

  17. Atrial Septal Defect (For Parents)

    Science.gov (United States)

    ... Video) Going to the Hospital Your Heart & Circulatory System Quiz: Heart & Circulatory System EKG (Video) What's It Like to Have Surgery? Atrial Septal Defect Ventricular Septal Defect Heart and Circulatory System Anesthesia Basics Contact Us Print Resources Send to ...

  18. Common Types of Heart Defects

    Science.gov (United States)

    ... heart –body. More information about Single Ventricle Defects . Tetralogy of Fallot What is it? A heart defect that features ... right chamber becomes overly thickened More information about Tetralogy of Fallot . Total Anomalous Pulmonary Venous Connection (TAPVC) What is ...

  19. Striatal neurodevelopment is dysregulated in purine metabolism deficiency and impacts DARPP-32, BDNF/TrkB expression and signaling: new insights on the molecular and cellular basis of Lesch-Nyhan Syndrome.

    Directory of Open Access Journals (Sweden)

    Ghiabe-Henri Guibinga

    Full Text Available Lesch-Nyhan Syndrome (LNS is a neurodevelopmental disorder caused by mutations in the gene encoding the purine metabolic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT. This syndrome is characterized by an array of severe neurological impairments that in part originate from striatal dysfunctions. However, the molecular and cellular mechanisms underlying these dysfunctions remain largely unidentified. In this report, we demonstrate that HPRT-deficiency causes dysregulated expression of key genes essential for striatal patterning, most notably the striatally-enriched transcription factor B-cell leukemia 11b (Bcl11b. The data also reveal that the down-regulated expression of Bcl11b in HPRT-deficient immortalized mouse striatal (STHdh neural stem cells is accompanied by aberrant expression of some of its transcriptional partners and other striatally-enriched genes, including the gene encoding dopamine- and cAMP-regulated phosphoprotein 32, (DARPP-32. Furthermore, we demonstrate that components of the BDNF/TrkB signaling, a known activator of DARPP-32 striatal expression and effector of Bcl11b transcriptional activation are markedly increased in HPRT-deficient cells and in the striatum of HPRT knockout mouse. Consequently, the HPRT-deficient cells display superior protection against reactive oxygen species (ROS-mediated cell death upon exposure to hydrogen peroxide. These findings suggest that the purine metabolic defect caused by HPRT-deficiency, while it may provide neuroprotection to striatal neurons, affects key genes and signaling pathways that may underlie the neuropathogenesis of LNS.

  20. BDNF Val66Met polymorphism, energy intake and BMI: a follow-up study in schoolchildren at risk of eating disorders

    OpenAIRE

    Aranda Nuria; Ferrer-Barcala Marta; Arija Victoria; Canals Josepa

    2010-01-01

    Abstract Background Eating disorders (ED) have a multifactorial aetiology in which genetics play an important role. Several studies have found an association between the Val66Met (G196A) polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) and Eating disorders. The aim of this study was to determine the association of the Val66Met (G196A) polymorphism of the BDNF gene and its effect on eating disorders (ED), energy intake and BMI in schoolchildren. Methods Two-year cohort study (pread...