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Sample records for bdnf transport defect

  1. 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

    BDNF levels in patients with parkinsonism. Twenty-one patients with abnormal in vivo striatal dopamine transporter (DAT) binding as evidenced with [(123)I]PE2I SPECT brain scanning were included. Samples for serum BDNF levels were collected at the time of the SPECT scanning, and BDNF was measured...

  2. Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Bianca Seifert

    2016-01-01

    Full Text Available The neurotrophin brain derived neurotrophic factor (BDNF is an important growth factor in the CNS. Deficits in transport of this secretory protein could underlie neurodegenerative diseases. Investigation of disease-related changes in BDNF transport might provide insights into the cellular mechanism underlying, for example, Alzheimer’s disease (AD. To analyze the role of BDNF transport in AD, live cell imaging of fluorescently labeled BDNF was performed in hippocampal neurons of different AD model systems. BDNF and APP colocalized with low incidence in vesicular structures. Anterograde as well as retrograde transport of BDNF vesicles was reduced and these effects were mediated by factors released from hippocampal neurons into the extracellular medium. Transport of BDNF was altered at a very early time point after onset of human APP expression or after acute amyloid-beta(1-42 treatment, while the activity-dependent release of BDNF remained unaffected. Taken together, extracellular cleavage products of APP induced rapid changes in anterograde and retrograde transport of BDNF-containing vesicles while release of BDNF was unaffected by transgenic expression of mutated APP. These early transport deficits might lead to permanently impaired brain functions in the adult brain.

  3. 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(2A......)) 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...... 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....

  4. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. BDNF val66met association with serotonin transporter binding in healthy humans

    DEFF Research Database (Denmark)

    Fisher, P. M.; Ozenne, B.; Svarer, C.

    2017-01-01

    -carriers have increased subcortical 5-HTT binding. The small difference suggests limited statistical power may explain previously reported null effects. Our finding adds to emerging evidence that BDNF val66met contributes to differences in the human brain serotonin system, informing how variability in the 5-HTT......The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted...

  6. BDNF val66met association with serotonin transporter binding in healthy humans

    OpenAIRE

    Fisher, P. M.; Ozenne, B.; Svarer, C.; Adamsen, D.; Lehel, S.; Baaré, W. F. C.; Jensen, P.S.; Knudsen, G. M.

    2017-01-01

    The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted differences in 5-HTT levels in humans but with equivocal results, possibly due to limited sample sizes. Within the current study we evaluated these genetic predictors of 5-HTT binding with [11C]DASB po...

  7. BDNF val66met association with serotonin transporter binding in healthy humans.

    Science.gov (United States)

    Fisher, P M; Ozenne, B; Svarer, C; Adamsen, D; Lehel, S; Baaré, W F C; Jensen, P S; Knudsen, G M

    2017-02-14

    The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted differences in 5-HTT levels in humans but with equivocal results, possibly due to limited sample sizes. Within the current study we evaluated these genetic predictors of 5-HTT binding with [ 11 C]DASB positron emission tomography (PET) in a comparatively large cohort of 144 healthy individuals. We used a latent variable model to determine genetic effects on a latent variable (5-HTT LV ), reflecting shared correlation across regional 5-HTT binding (amygdala, caudate, hippocampus, midbrain, neocortex, putamen and thalamus). Our data supported a significant BDNF val66met effect on 5-HTT LV such that met-carriers showed 2-7% higher subcortical 5-HTT binding compared with val/val individuals (P=0.042). Our data did not support a BDNF val66met effect in neocortex and 5-HTTLPR did not significantly predict 5-HTT LV . We did not observe evidence for an interaction between genotypes. Our findings indicate that met-carriers have increased subcortical 5-HTT binding. The small difference suggests limited statistical power may explain previously reported null effects. Our finding adds to emerging evidence that BDNF val66met contributes to differences in the human brain serotonin system, informing how variability in the 5-HTT level emerges and may represent an important molecular mediator of BDNF val66met effects on behavior and related risk for neuropsychiatric illness.

  8. 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...

  9. Reduced function of the serotonin transporter is associated with decreased expression of BDNF in rodents as well as in humans.

    NARCIS (Netherlands)

    Molteni, R.; Cattaneo, A.; Calabrese, F.; Macchi, F.; Olivier, J.D.A.; Racagni, G.; Ellenbroek, A.A.; Gennarelli, M.; Riva, M.A.

    2010-01-01

    In order to identify the molecular mechanisms that may contribute to the enhanced susceptibility to depression under serotonin transporter (SERT) dysfunction, we analyzed the expression of brain-derived neurotrophic factor (BDNF), a key player in neuronal plasticity, which is implicated in the

  10. Point defects and atomic transport in crystals

    International Nuclear Information System (INIS)

    Lidiard, A.B.

    1981-02-01

    There are two principle aspects to the theory of atomic transport in crystals as caused by the action of point defects, namely (1) the calculation of relevant properties of the point defects (energies and other thermodynamic characteristics of the different possible defects, activation energies and other mobility parameters) and (2) the statistical mechanics of assemblies of defects, both equilibrium and non-equilibrium assemblies. In the five lectures given here both these aspects are touched on. The first two lectures are concerned with the calculation of relevant point defect properties, particularly in ionic crystals. The first lecture is more general, the second is concerned particularly with some recent calculations of the free volumes of formation of defects in various ionic solids; these solve a rather long-standing problem in this area. The remaining three lectures are concerned with the kinetic theory of defects mainly in relaxation, drift and diffusion situations

  11. Study of the serotonin transporter (SLC6A4) and BDNF genes in French patients with non syndromic mental deficiency.

    Science.gov (United States)

    Tabagh, Refaat; Andres, Christian R; Védrine, Sylviane; Cherpi-Antar, Catherine; Thepault, Rose-Anne; Mignon, Laurence; Dufour-Rainfray, Diane; Moraine, Claude; Vourc'h, Patrick

    2010-02-22

    Mental deficiency has been linked to abnormalities in cortical neuronal network connectivity and plasticity. These mechanisms are in part under the control of two interacting signalling pathways, the serotonergic and the brain-derived neurotrophic (BDNF) pathways. The aim of the current paper is to determine whether particular alleles or genotypes of two crucial genes of these systems, the serotonin transporter gene (SLC6A4) and the brain-derived neurotrophic factor gene (BDNF), are associated with mental deficiency (MD). We analyzed four functional polymorphisms (rs25531, 5-HTTLPR, VNTR, rs3813034) of the SLC6A4 gene and one functional polymorphism (Val66 Met) of the BDNF gene in 98 patients with non-syndromic mental deficiency (NS-MD) and in an ethnically matched control population of 251 individuals. We found no significant differences in allele and genotype frequencies in the five polymorphisms studied in the SLC6A4 and BDNF genes of NS-MD patients versus control patients. While the comparison of the patterns of linkage disequilibrium (D') in the control and NS-MD populations revealed a degree of variability it did not, however, reach significance. No significant differences in frequencies of haplotypes and genotypes for VNTR/rs3813034 and rs25531/5-HTTLPR were observed. Altogether, results from the present study do not support a role for any of the five functional polymorphisms of SLC6A4 and BDNF genes in the aetiology of NS-RM. Moreover, they suggest no epistatic interaction in NS-MD between polymorphisms in BDNF and SLC6A4. However, we suggest that further studies on these two pathways in NS-MD remain necessary.

  12. Study of the serotonin transporter (SLC6A4 and BDNF genes in French patients with non syndromic mental deficiency

    Directory of Open Access Journals (Sweden)

    Mignon Laurence

    2010-02-01

    Full Text Available Abstract Background Mental deficiency has been linked to abnormalities in cortical neuronal network connectivity and plasticity. These mechanisms are in part under the control of two interacting signalling pathways, the serotonergic and the brain-derived neurotrophic (BDNF pathways. The aim of the current paper is to determine whether particular alleles or genotypes of two crucial genes of these systems, the serotonin transporter gene (SLC6A4 and the brain-derived neurotrophic factor gene (BDNF, are associated with mental deficiency (MD. Methods We analyzed four functional polymorphisms (rs25531, 5-HTTLPR, VNTR, rs3813034 of the SLC6A4 gene and one functional polymorphism (Val66 Met of the BDNF gene in 98 patients with non-syndromic mental deficiency (NS-MD and in an ethnically matched control population of 251 individuals. Results We found no significant differences in allele and genotype frequencies in the five polymorphisms studied in the SLC6A4 and BDNF genes of NS-MD patients versus control patients. While the comparison of the patterns of linkage disequilibrium (D' in the control and NS-MD populations revealed a degree of variability it did not, however, reach significance. No significant differences in frequencies of haplotypes and genotypes for VNTR/rs3813034 and rs25531/5-HTTLPR were observed. Conclusion Altogether, results from the present study do not support a role for any of the five functional polymorphisms of SLC6A4 and BDNF genes in the aetiology of NS-RM. Moreover, they suggest no epistatic interaction in NS-MD between polymorphisms in BDNF and SLC6A4. However, we suggest that further studies on these two pathways in NS-MD remain necessary.

  13. Changes in Expression of Dopamine, Its Receptor, and Transporter in Nucleus Accumbens of Heroin-Addicted Rats with Brain-Derived Neurotrophic Factor (BDNF) Overexpression.

    Science.gov (United States)

    Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Liang, Wenmei

    2017-06-09

    BACKGROUND The aim of this study was to explore how changes in the expression of BDNF in MLDS change the effect of BDNF on dopamine (DA) neurons, which may have therapeutic implications for heroin addiction. MATERIAL AND METHODS We established a rat model of heroin addiction and observed changes in the expression of BDNF, DA, dopamine receptor (DRD), dopamine transporter (DAT), and other relevant pathways in NAc. We also assessed the effect of BDNF overexpression in the NAc, behavioral changes of heroin-conditioned place preference (CPP), and naloxone withdrawal in rats with high levels of BDNF. We established 5 adult male rat groups: heroin addiction, lentivirus transfection, blank virus, sham operation, and control. The PCR gene chip was used to study gene expression changes. BDNF lentivirus transfection was used for BDNF overexpression. A heroin CPP model and a naloxone withdrawal model of rats were established. RESULTS Expression changes were found in 20 of the 84 DA-associated genes in the NAc of heroin-addicted rats. Weight loss and withdrawal symptoms in the lentivirus group for naloxone withdrawal was less than in the blank virus and the sham operation group. These 2 latter groups also showed significant behavioral changes, but such changes were not observed in the BDNF lentivirus group before or after training. DRD3 and DAT increased in the NAc of the lentivirus group. CONCLUSIONS BDNF and DA in the NAc are involved in heroin addiction. BDNF overexpression in NAc reduces withdrawal symptoms and craving behavior for medicine induced by environmental cues for heroin-addicted rats. BDNF participates in the regulation of the dopamine system by acting on DRD3 and DAT.

  14. 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

  15. Anisotropic bias dependent transport property of defective phosphorene layer

    Science.gov (United States)

    Umar Farooq, M.; Hashmi, Arqum; Hong, Jisang

    2015-01-01

    Phosphorene is receiving great research interests because of its peculiar physical properties. Nonetheless, no systematic studies on the transport properties modified due to defects have been performed. Here, we present the electronic band structure, defect formation energy and bias dependent transport property of various defective systems. We found that the defect formation energy is much less than that in graphene. The defect configuration strongly affects the electronic structure. The band gap vanishes in single vacancy layers, but the band gap reappears in divacancy layers. Interestingly, a single vacancy defect behaves like a p-type impurity for transport property. Unlike the common belief, we observe that the vacancy defect can contribute to greatly increasing the current. Along the zigzag direction, the current in the most stable single vacancy structure was significantly increased as compared with that found in the pristine layer. In addition, the current along the armchair direction was always greater than along the zigzag direction and we observed a strong anisotropic current ratio of armchair to zigzag direction. PMID:26198318

  16. Effect of hydrophilic defects on water transport in MFI zeolites.

    Science.gov (United States)

    Humplik, Thomas; Raj, Rishi; Maroo, Shalabh C; Laoui, Tahar; Wang, Evelyn N

    2014-06-10

    The subnanometer pore structure of zeolites and other microporous materials has been proposed to act as a molecular sieve for various water separation technologies. However, due to the increased interaction between the solid and water in these nanoconfined spaces, it is unclear which type of interface, be it hydrophilic or hydrophobic, offers an advantageous medium for enhancing transport properties. In this work, we probe the role of hydrophilic defects on the transport of water inside the microporous hydrophobic MFI zeolite pore structure via combined sorption and high-pressure infiltration experiments. While the inclusion of defects was observed to increase the amount of water within the zeolite pore network by up to 7 times at the saturation pressure, the diffusivity of this infiltrated water was lowered by up to 2 orders of magnitude in comparison to that of water within the nearly defect-free hydrophobic MFI zeolite. Subsequently, the permeability of water within the more defective MFI zeolite was an order of magnitude lower than that of the nearly defect-free zeolite. The results from these experiments suggest that the intrinsic hydrophobic pore structure of MFI zeolites can facilitate faster water transport due to the decreased attraction between the water and the defect-free surface. While the strong attraction of water to the defects allows for water to infiltrate the porous network at lower pressures, the results suggest that this strong attraction decreases the mobility of the infiltrated water. The insights gained from this study can be utilized to improve the design of future membranes for water desalination and other separation techniques.

  17. Modelling of transport phenomena and defects in crystal growth ...

    Indian Academy of Sciences (India)

    A brief review of single crystal growth techniques and the associated problems is presented. Emphasis is placed on models for various transport and defect phenomena involoved in the growth process with the ultimate aim of integrating them into a comprehensive numerical model. The sources of dislocation nucleation in ...

  18. 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.

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

    International Nuclear Information System (INIS)

    Iqbal, A.; Amin, M.S.

    2002-01-01

    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 m ean 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

  20. Quantum transport in defective phosphorene nanoribbons: Effects of atomic vacancies

    Science.gov (United States)

    Li, L. L.; Peeters, F. M.

    2018-02-01

    Defects are almost inevitably present in realistic materials and defective materials are expected to exhibit very different properties than their nondefective (perfect) counterparts. Here, using a combination of the tight-binding approach and the scattering matrix formalism, we investigate the electronic transport properties of defective phosphorene nanoribbons (PNRs) containing atomic vacancies. We find that for both armchair PNRs (APNRs) and zigzag PNRs (ZPNRs), single vacancies can create quasilocalized states, which can affect their conductance. With increasing vacancy concentration, three different transport regimes are identified: ballistic, diffusive, and Anderson localized ones. In particular, ZPNRs that are known to be metallic due to the presence of edge states become semiconducting: edge conductance vanishes and transport gap appears due to Anderson localization. Moreover, we find that for a fixed vacancy concentration, both APNRs and ZPNRs of narrower width and/or longer length are more sensitive to vacancy disorder than their wider and/or shorter counterparts, and that for the same ribbon length and width, ZPNRs are more sensitive to vacancy disorder than APNRs.

  1. Harsh Parenting and Serotonin Transporter and BDNF Val66Met Polymorphisms as Predictors of Adolescent Depressive Symptoms.

    Science.gov (United States)

    Koss, Kalsea J; Cummings, E Mark; Davies, Patrick T; Hetzel, Susan; Cicchetti, Dante

    2016-10-13

    Depressive symptoms are prevalent and rise during adolescence. The present study is a prospective investigation of environmental and genetic factors that contribute to the growth in depressive symptoms and the frequency of heightened symptoms during adolescence. Participants included 206 mother-father-adolescent triads (M age at Time 1 = 13.06 years, SD = .51, 52% female). Harsh parenting was observationally assessed during a family conflict paradigm. DNA was extracted from saliva samples and genotyped for the 5-HTTLPR and BDNF Val66Met polymorphisms. Adolescents provide self-reports of depressive symptoms annually across early adolescence. The results reveal Gene × Environment interactions as predictors of adolescent depressive symptom trajectories in the context of harsh parenting as an environmental risk factor. A BDNF Val66Met × Harsh Parenting interaction predicted the rise in depressive symptoms across a 3-year period, whereas a 5-HTTLPR × Harsh Parenting interaction predicted greater frequency in elevated depressive symptoms. The findings highlight the importance of unique genetic and environmental influences in the development and course of heightened depressive symptoms during adolescence.

  2. Accurate modeling of defects in graphene transport calculations

    Science.gov (United States)

    Linhart, Lukas; Burgdörfer, Joachim; Libisch, Florian

    2018-01-01

    We present an approach for embedding defect structures modeled by density functional theory into large-scale tight-binding simulations. We extract local tight-binding parameters for the vicinity of the defect site using Wannier functions. In the transition region between the bulk lattice and the defect the tight-binding parameters are continuously adjusted to approach the bulk limit far away from the defect. This embedding approach allows for an accurate high-level treatment of the defect orbitals using as many as ten nearest neighbors while keeping a small number of nearest neighbors in the bulk to render the overall computational cost reasonable. As an example of our approach, we consider an extended graphene lattice decorated with Stone-Wales defects, flower defects, double vacancies, or silicon substitutes. We predict distinct scattering patterns mirroring the defect symmetries and magnitude that should be experimentally accessible.

  3. The electronic and transport properties of borophane with defects: A first principles study

    Science.gov (United States)

    Sun, Jie; Zhang, Yujin; Leng, Jiancai; Ma, Hong

    2018-03-01

    Recent works well confirm the stability of hydrogenated borophene, known as borophane. Here, first principles studies have performed on the electronic and transport properties of borophane with defects. The calculations indicate that the introduction of defects results in different behavior of charges redistribution along x and y directions. The intrinsic electronic structure of borophane with Dirac cone is destroyed in various degrees by each type of defect. The inducing defect states lead to the occurrence of flat bands, which are not benefit for the electronic transport properties. According to the transmission spectra and I-V characteristics, these defects decrease the transmission intensity and the current value both along two directions. However, the transport anisotropy can be efficiently tuned by defect, which may contribute to the design of functional device.

  4. 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

  5. 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...

  6. Effect of Transport Distance and Season on Some Defects of Fresh Hams Destined for DPO Production

    Science.gov (United States)

    Arduini, Agnese; Redaelli, Veronica; Luzi, Fabio; Dall’Olio, Stefania; Pace, Vincenzo; Nanni Costa, Leonardo

    2014-01-01

    Simple Summary Transport to the slaughterhouse is a stressful event for pigs. Travel duration and conditions can negatively affect animal welfare and carcass quality. Some defects in fresh hams are strictly connected to pre-slaughter transportation. Journeys with short (170 km) distances may increase damage in fresh hams and decrease Denomination Protected of Origin (DPO) Parma dry-cured ham production. Abstract Pre-slaughter handling is related to defects in fresh hams that result in exclusion from the DPO Parma chain, including hematomas, lacerations, microhaemorrhages and veining. To determine the effects of transport conditions on hams, we collected data on defects in 901,990 trimmed fresh hams from heavy pigs provided by 3,650 batches from slaughterhouse during 2012 and 2013. For all batches, transport distance (1–276 km) season and year of delivery were considered. A decrease of all defect occurrences was observed for increasing distance up to 170 km (P < 0.05). Above 170 km, however, all defects frequencies increased (P < 0.05). Season showed an effect on the incidence of defects, with an increasing of hematomas and lacerations in winter and autumn respectively (P < 0.05) and the highest percentage of veining and hemorrhages in spring (P < 0.05). Summer had the lowest incidence of defects on fresh hams. We concluded that the incidence of the examined defects and the subsequent rejection for DPO Parma ham production is lower in fresh hams transported 38–170 km during the summer. PMID:26480322

  7. Electronic transport properties of 1D-defects in graphene and other 2D-systems

    Energy Technology Data Exchange (ETDEWEB)

    Willke, P.; Wenderoth, M. [IV. Physical Institute, Solids and Nanostructures, Georg-August-University Goettingen (Germany); Schneider, M.A. [Lehrstuhl fuer Festkoerperphysik, Universitaet Erlangen-Nuernberg, Erlangen (Germany)

    2017-11-15

    The continuous progress in device miniaturization demands a thorough understanding of the electron transport processes involved. The influence of defects - discontinuities in the perfect and translational invariant crystal lattice - plays a crucial role here. For graphene in particular, they limit the carrier mobility often demanded for applications by contributing additional sources of scattering to the sample. Due to its two-dimensional nature graphene serves as an ideal system to study electron transport in the presence of defects, because one-dimensional defects like steps, grain boundaries and interfaces are easy to characterize and have profound effects on the transport properties. While their contribution to the resistance of a sample can be extracted by carefully conducted transport experiments, scanning probe methods are excellent tools to study the influence of defects locally. In this letter, the authors review the results of scattering at local defects in graphene and other 2D systems by scanning tunneling potentiometry, 4-point-probe microscopy, Kelvin probe force microscopy and conventional transport measurements. Besides the comparison of the different defect resistances important for device fabrication, the underlying scattering mechanisms are discussed giving insight into the general physics of electron scattering at defects. (copyright 2017 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

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

    Science.gov (United States)

    Appert-Rolland, C.; Ebbinghaus, M.; Santen, L.

    2015-09-01

    Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized. The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the 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. The interest for this type of question was enhanced when it was discovered that intracellular transport 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. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the

  9. BDNF-induced local protein synthesis and synaptic plasticity.

    Science.gov (United States)

    Leal, Graciano; Comprido, Diogo; Duarte, Carlos B

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and long-term potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-γ (PLC-γ) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre- and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short- and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Method to mount defect fuel elements i transport casks

    International Nuclear Information System (INIS)

    Borgers, H.; Deleryd, R.

    1996-01-01

    Leaching or otherwise failed fuel elements are mounted in special containers that fit into specially designed chambers in a transportation cask for transport to reprocessing or long-time storage. The fuel elements are entered into the container under water in a pool. The interior of the container is dried before transfer to the cask. Before closing the cask, its interior, and the exterior of the container are dried. 2 figs

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

    Energy Technology Data Exchange (ETDEWEB)

    Wampler, William R.; Myers, Samuel Maxwell,

    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.

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

    International Nuclear Information System (INIS)

    Chiodelli, G.; Consiglio Nazionale delle Ricerche, Pavia; Anselmi-Tamburini, U.; Consiglio Nazionale delle Ricerche, Pavia; Arimondi, M.; Consiglio Nazionale delle Ricerche, Pavia; Spinolo, G.; Consiglio Nazionale delle Ricerche, Pavia; Flor, G.; Consiglio Nazionale delle Ricerche, Pavia

    1995-01-01

    The charge transport properties of ''BaCuO 2 '' 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.)

  13. Point defect and transport parameters in the CsI-TlI solid solution

    International Nuclear Information System (INIS)

    Schiraldi, A.; Pezzati, E.; Rossi, P.

    1980-01-01

    Transport and point defect parameters of the solid solution CsI-TlI have been obtained through the already reported semiempirical approach. However in this case preliminary calculations concerning pure cubic TlI have been necessary: ionic migration and point defect formation energies in this salt have been attained by working out experimental data and by applying a simplified Boswara-Lidiard approach, respectively. As well as in the analogous systems, CsBr-TlBr and CsCl-TlCl, the role of the point defect concentration seems more relevant than that of the ionic mobility in determining the trend of the conductivity vs composition. (orig.) [de

  14. The electronic transport properties of defected bilayer sliding armchair graphene nanoribbons

    Science.gov (United States)

    Mohammadi, Amin; Haji-Nasiri, Saeed

    2018-04-01

    By applying non-equilibrium Green's functions (NEGF) in combination with tight-binding (TB) model, we investigate and compare the electronic transport properties of perfect and defected bilayer armchair graphene nanoribbons (BAGNRs) under finite bias. Two typical defects which are placed in the middle of top layer (i.e. single vacancy (SV) and stone wale (SW) defects) are examined. The results reveal that in both perfect and defected bilayers, the maximum current refers to β-AB, AA and α-AB stacking orders, respectively, since the intermolecular interactions are stronger in them. Moreover it is observed that a SV decreases the current in all stacking orders, but the effects of a SW defect is nearly unpredictable. Besides, we introduced a sequential switching behavior and the effects of defects on the switching performance is studied as well. We found that a SW defect can significantly improve the switching behavior of a bilayer system. Transmission spectrum, band structure, molecular energy spectrum and molecular projected self-consistent Hamiltonian (MPSH) are analyzed subsequently to understand the electronic transport properties of these bilayer devices which can be used in developing nano-scale bilayer systems.

  15. Defect-Engineered Heat Transport in Graphene: A Route to High Efficient Thermal Rectification

    Science.gov (United States)

    Zhao, Weiwei; Wang, Yanlei; Wu, Zhangting; Wang, Wenhui; Bi, Kedong; Liang, Zheng; Yang, Juekuan; Chen, Yunfei; Xu, Zhiping; Ni, Zhenhua

    2015-07-01

    Low-dimensional materials such as graphene provide an ideal platform to probe the correlation between thermal transport and lattice defects, which could be engineered at the molecular level. In this work, we perform molecular dynamics simulations and non-contact optothermal Raman measurements to study this correlation. We find that oxygen plasma treatment could reduce the thermal conductivity of graphene significantly even at extremely low defect concentration (˜83% reduction for ˜0.1% defects), which could be attributed mainly to the creation of carbonyl pair defects. Other types of defects such as hydroxyl, epoxy groups and nano-holes demonstrate much weaker effects on the reduction where the sp2 nature of graphene is better preserved. With the capability of selectively functionalizing graphene, we propose an asymmetric junction between graphene and defective graphene with a high thermal rectification ratio of ˜46%, as demonstrated by our molecular dynamics simulation results. Our findings provide fundamental insights into the physics of thermal transport in defective graphene, and two-dimensional materials in general, which could help on the future design of functional applications such as optothermal and electrothermal devices.

  16. Study of irradiation defects in bismuth by electric transport measurements

    International Nuclear Information System (INIS)

    Le Goff, M.

    1984-01-01

    Pure monocrystalline bismuth is irradiated near 4K by electrons of different energies. Irradiation effects are measured by galvanomagnetic properties at low temperature. Frenkel pairs created during irradiation have a strong effect on carrier mobilities. The data are quantitatively analyzed assuming a rigid band model. After irradiation with 1 MeV electrons, each Frankel pair created corresponds to a total charge of 0.14 electrons. This result obtained by magnetoresistance and Hall effect is confirmed by Shubnikov-de Haas experiments. There is a linear variation between the excess carrier density (p-n) and the Frenkel pair concentration. The more important step of annealing is observed around 40-50 K. This step is attributed to interstitial migration. Resistivity presents a minimum at low temperature after irradiation with electrons of energy over 1.3 MeV. This is explained by virtual bound levels near the Fermi level. The Kondo effect bound to magnetic defects is discussed [fr

  17. Ab initio phonon point defect scattering and thermal transport in graphene

    Science.gov (United States)

    Polanco, Carlos A.; Lindsay, Lucas

    2018-01-01

    We study the scattering of phonons from point defects and their effect on lattice thermal conductivity κ using a parameter-free ab initio Green's function methodology. Specifically, we focus on the scattering of phonons by boron (B), nitrogen (N), and phosphorus substitutions as well as single- and double-carbon vacancies in graphene. We show that changes of the atomic structure and harmonic interatomic force constants locally near defects govern the strength and frequency trends of the scattering of out-of-plane acoustic (ZA) phonons, the dominant heat carriers in graphene. ZA scattering rates due to N substitutions are nearly an order of magnitude smaller than those for B defects despite having similar mass perturbations. Furthermore, ZA phonon scattering rates from N defects decrease with increasing frequency in the lower-frequency spectrum in stark contrast to expected trends from simple models. ZA phonon-vacancy scattering rates are found to have a significantly softer frequency dependence (˜ω0 ) in graphene than typically employed in phenomenological models. The rigorous Green's function calculations demonstrate that typical mass-defect models do not adequately describe ZA phonon-defect scattering rates. Our ab initio calculations capture well the trend of κ vs vacancy density from experiments, though not the magnitudes. This work elucidates important insights into phonon-defect scattering and thermal transport in graphene, and demonstrates the applicability of first-principles methods toward describing these properties in imperfect materials.

  18. 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

    2016-04-07

    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.

  19. 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.

  20. Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity.

    Directory of Open Access Journals (Sweden)

    Laura Jeacock

    2017-03-01

    Full Text Available Aquaglyceroporins (AQPs transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM, octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited.

  1. Neurobiology of axonal transport defects in motor neuron diseases: Opportunities for translational research?

    Science.gov (United States)

    De Vos, Kurt J; Hafezparast, Majid

    2017-09-01

    Intracellular trafficking of cargoes is an essential process to maintain the structure and function of all mammalian cell types, but especially of neurons because of their extreme axon/dendrite polarisation. Axonal transport mediates the movement of cargoes such as proteins, mRNA, lipids, membrane-bound vesicles and organelles that are mostly synthesised in the cell body and in doing so is responsible for their correct spatiotemporal distribution in the axon, for example at specialised sites such as nodes of Ranvier and synaptic terminals. In addition, axonal transport maintains the essential long-distance communication between the cell body and synaptic terminals that allows neurons to react to their surroundings via trafficking of for example signalling endosomes. Axonal transport defects are a common observation in a variety of neurodegenerative diseases, and mutations in components of the axonal transport machinery have unequivocally shown that impaired axonal transport can cause neurodegeneration (reviewed in El-Kadi et al., 2007, De Vos et al., 2008; Millecamps and Julien, 2013). Here we review our current understanding of axonal transport defects and the role they play in motor neuron diseases (MNDs) with a specific focus on the most common form of MND, amyotrophic lateral sclerosis (ALS). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. 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

    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...... 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. (C) 2014 AIP Publishing LLC.......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...

  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 ...... positive correlation between frontal cortex and hippocampal BDNF levels in mice (r2=0.81, p=0.0139). Our data support the view that measures of blood and plasma BDNF levels reflect brain-tissue BDNF levels....

  4. Electron scattering in graphene by defects in underlying h-BN layer: First-principles transport calculations

    Science.gov (United States)

    Kaneko, Tomoaki; Ohno, Takahisa

    2018-03-01

    We investigate the electronic structure and the transport properties of graphene adsorbed onto h-BN with carbon impurities or atomic vacancies using density functional theory and the non-equilibrium Green's function method. We find that the transport properties are degraded due to carrier doping and scattering off of localized defect states in h-BN. When graphene is doped by introducing defects in h-BN, the transmission spectra become asymmetric owing to the reduction of the electronic density of states, which contributes significantly to the degradation of graphene transport properties as compared with the effect of defect levels.

  5. 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

  6. 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...... tunneling spectroscopy (IETS) of long pristine and defective armchair and zigzag nanoribbons under a range of charge carrier conditions. For the armchair ribbons we find two robust IETS signals around 169 and 196 mV corresponding to the D and G modes of Raman spectroscopy as well as additional fingerprints...... due to various types of defects in the edge passivation. For the zigzag ribbons we show that the spin state strongly influences the spectrum and thus propose IETS as an indirect proof of spin polarization....

  7. 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

    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...... positive correlation between frontal cortex and hippocampal BDNF levels in mice (r2=0.81, p=0.0139). Our data support the view that measures of blood and plasma BDNF levels reflect brain-tissue BDNF levels....

  8. BDNF in fragile X syndrome.

    Science.gov (United States)

    Castrén, Maija L; Castrén, Eero

    2014-01-01

    Fragile X syndrome (FXS) is a monogenic disorder that is caused by the absence of FMR1 protein (FMRP). FXS serves as an excellent model disorder for studies investigating disturbed molecular mechanisms and synapse function underlying cognitive impairment, autism, and behavioral disturbance. Abnormalities in dendritic spines and synaptic transmission in the brain of FXS individuals and mouse models for FXS indicate perturbations in the development, maintenance, and plasticity of neuronal network connectivity. However, numerous alterations are found during the early development in FXS, including abnormal differentiation of neural progenitors and impaired migration of newly born neurons. Several aspects of FMRP function are modulated by brain-derived neurotrophic factor (BDNF) signaling. Here, we review the evidence of the role for BDNF in the developing and adult FXS brain. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  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

    2016-08-04

    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. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Single Particle Transport Through Carbon Nanotube Wires: Effect of Defects and Polyhedral Cap

    Science.gov (United States)

    Anantram, M. P.; Govidan, T. R.

    1999-01-01

    The ability to manipulate carbon nanotubes with increasing precision has enabled a large number of successful electron transport experiments. These studies have primarily focussed on characterizing transport through both metallic and semiconducting wires. Tans et al. demonstrated ballistic transport in single-wall nanotubes for the first time, although the experimental configuration incurred large contact resistance. Subsequently, methods of producing low contact resistances have been developed and two terminal conductances smaller than 50 k-ohms have been repeatably demonstrated in single-wall and multi-wall nanotubes. In multi-wall nanotubes, Frank et al. demonstrated a resistance of approximately h/2e(exp 2) in a configuration where the outermost layer made contact to a liquid metal. This was followed by the work of de Pablo et al. where a resistance of h(bar)/27e(exp 2) (approximately 478 ohms) was measured in a configuration where electrical contact was made to many layers of a multi-wall nanotube. Frank et al. and Pablo et al. note that each conducting layer contributes a conductance of only 2e(exp 2)/h, instead of the 4e(exp 2)/h that a single particle mode counting picture yields. These small resistances have been obtained in microns long nanotubes, making them the best conducting molecular wires to date. The large conductance of nanotube wires stems from the fact that the crossing bands of nanotubes are robust to defect scattering.

  11. 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.

  12. Impact of defects on the electrical transport, optical properties and failure mechanisms of GaN nanowires.

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Andrew M.; Aubry, Sylvie; Shaner, Eric Arthur; Siegal, Michael P.; Li, Qiming; Jones, Reese E.; Westover, Tyler; Wang, George T.; Zhou, Xiao Wang; Talin, Albert Alec; Bogart, Katherine Huderle Andersen; Harris, C. Thomas; Huang, Jian Yu

    2010-09-01

    We present the results of a three year LDRD project that focused on understanding the impact of defects on the electrical, optical and thermal properties of GaN-based nanowires (NWs). We describe the development and application of a host of experimental techniques to quantify and understand the physics of defects and thermal transport in GaN NWs. We also present the development of analytical models and computational studies of thermal conductivity in GaN NWs. Finally, we present an atomistic model for GaN NW electrical breakdown supported with experimental evidence. GaN-based nanowires are attractive for applications requiring compact, high-current density devices such as ultraviolet laser arrays. Understanding GaN nanowire failure at high-current density is crucial to developing nanowire (NW) devices. Nanowire device failure is likely more complex than thin film due to the prominence of surface effects and enhanced interaction among point defects. Understanding the impact of surfaces and point defects on nanowire thermal and electrical transport is the first step toward rational control and mitigation of device failure mechanisms. However, investigating defects in GaN NWs is extremely challenging because conventional defect spectroscopy techniques are unsuitable for wide-bandgap nanostructures. To understand NW breakdown, the influence of pre-existing and emergent defects during high current stress on NW properties will be investigated. Acute sensitivity of NW thermal conductivity to point-defect density is expected due to the lack of threading dislocation (TD) gettering sites, and enhanced phonon-surface scattering further inhibits thermal transport. Excess defect creation during Joule heating could further degrade thermal conductivity, producing a viscous cycle culminating in catastrophic breakdown. To investigate these issues, a unique combination of electron microscopy, scanning luminescence and photoconductivity implemented at the nanoscale will be used in

  13. BDNF Val66Met homozygosity does not influence plasma BDNF levels in healthy human subjects

    NARCIS (Netherlands)

    Luykx, J.J.; Boks, M.P.M.; Breetvelt, E.J.; Aukes, M.F.; Strengman, E.; da Pozzo, E.; Dell'osso, L.; Marazziti, D.; van Leeuwen, A.; Vreeker, A.; Abramovic, L.; Martini, C.; Numans, M.E.; Kahn, R. S.; Ophoff, R. A.

    2013-01-01

    A putative pathway by which the BDNF Val66Met polymorphism (rs6265) leads to aberrant phenotypes is its influence on plasma BDNF. Research into the impact of rs6265 on plasma BDNF has given rise to conflicting results. Moreover, most such studies have compared Met-carriers with Val-homozygous

  14. Association Between Smoking, Nicotine Dependence, and BDNF Val(66)Met Polymorphism with BDNF Concentrations in Serum

    NARCIS (Netherlands)

    Jamal, Mumtaz; Van der Does, Willem; Elzinga, Bernet M.; Molendijk, Marc L.; Penninx, Brenda W. J. H.

    Introduction: Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers,

  15. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Measurement and modelling of the defect chemistry and transport properties of ceramic oxide mixed ionic and electronic conductors

    NARCIS (Netherlands)

    Dalslet, Bjarke Thomas

    2008-01-01

    The mixed ionic and electronic conducting fluorite and perovskite materials examined in this thesis are all oxide ion conducting materials. The defect chemistry and transport properties of a number of these materials are measured using: 1) a measurement technique using an oxygen pump and an

  17. The effect of childhood trauma on serum BDNF in bipolar depression is modulated by the serotonin promoter genotype.

    Science.gov (United States)

    Benedetti, Francesco; Ambrée, Oliver; Locatelli, Clara; Lorenzi, Cristina; Poletti, Sara; Colombo, Cristina; Arolt, Volker

    2017-08-24

    In healthy humans, both childhood trauma and the short form of the serotonin promoter transporter genotype (5-HTTLPR) are associated with lower levels of brain-derived neurotrophic factor (BDNF). In subjects with bipolar disorder (BD), lower levels of BDNF and a higher degree of childhood trauma were observed compared with healthy controls. However, is still unknown if the functional 5-HTTLPR polymorphisms exerts an effect on both abnormalities. In 40 inpatients affected by a major depressive episode in the course of BD, we genotyped 5-HTTLPR, measured serum BDNF with ELISA, and assessed early adversities by the childhood trauma questionnaire (CTQ). Data were analyzed in the context of the general linear model correcting for age, sex, ongoing lithium treatment, severity of current depression, and CTQ minimization/denial scores to investigate the effect of 5-HTTLPR polymorphism and childhood trauma on BDNF levels. Early trauma were negatively associated with BDNF serum levels (higher CTQ scores, lower BDNF; p=0.0019). 5-HTTLPR l/l homozygotes showed significantly higher BDNF levels than 5-HTTLPR*s carriers (30.57±6.13 vs 26.82±6.41; p=0.0309). A separate-slopes analysis showed that 5-HTTLPR significantly influenced the relationship between early trauma and adult BDNF (interaction of 5-HTTLPR with CTQ scores: p=0.0023), due to a significant relationship between trauma and BDNF in 5-HTTLPR*s carriers, but not among l/l homozygotes. Putatively detrimental effects of childhood trauma exposure on adult BDNF serum levels are influenced by 5-HTTLPR genotype in patients affected by BD. Possible mechanisms include epigenetic modulation of BDNF gene expression, due to different reactivity to stressors in 5-HTTLPR genotype groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Thermodynamics and transport of ionic and electronic defects in crystaline oxides

    NARCIS (Netherlands)

    Lankhorst, M.H.R.; Lankhorst, Martijn H.R.; Bouwmeester, Henricus J.M.; Verweij, H.

    1997-01-01

    The first part of this article concerns the thermodynamics of point defects. In the traditional analysis of reactions in which point defects are involved, point defects are assumed to be ideally diluted, which leads to familiar mass-action-type equations. In this article, situations in which

  19. Transport mechanisms through PE-CVD coatings: influence of temperature, coating properties and defects on permeation of water vapour

    International Nuclear Information System (INIS)

    Kirchheim, Dennis; Jaritz, Montgomery; Hopmann, Christian; Dahlmann, Rainer; Mitschker, Felix; Awakowicz, Peter; Gebhard, Maximilian; Devi, Anjana; Brochhagen, Markus; Böke, Marc

    2017-01-01

    Gas transport mechanisms through plastics are usually described by the temperature-dependent Arrhenius-model and compositions of several plastic layers are represented by the CLT. When it comes to thin films such as plasma-enhanced chemical vapour deposition (PE-CVD) or plasma-enhanced atomic layer deposition (PE-ALD) coatings on substrates of polymeric material, a universal model is lacking. While existing models describe diffusion through defects, these models presume that permeation does not occur by other means of transport mechanisms. This paper correlates the existing transport models with data from water vapour transmission experiments. (paper)

  20. 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.

  1. 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

  2. Effect of Native Defects on Transport Properties in Non-Stoichiometric CoSb₃.

    Science.gov (United States)

    Realyvázquez-Guevara, Paula R; Rivera-Gómez, Francisco J; Faudoa-Arzate, Alejandro; Botello-Zubiate, María E; Sáenz-Hernández, Renee J; Santillán-Rodríguez, Carlos R; Matutes-Aquino, José A

    2017-03-14

    The effect of native defects originated by a non-stoichiometric variation of composition in CoSb₃ on I-V curves and Hall effect was investigated. Hysteretic and a non-linear behavior of the  I-V curves at cryogenic temperatures were observed; the non-linear behavior originated from the Poole-Frenkel effect, a field-dependent ionization mechanism that lowers Coulomb barriers and increases emission of charge carriers, and the hysteresis was attributed to the drastic decrease of specific heat which produces Joule heating at cryogenic temperatures. CoSb₃ is a narrow gap semiconductor and slight variation in the synthesis process can lead to either n - or p -type conduction. The Sb-deficient CoSb₃ presented an n -type conduction. Using a single parabolic model and assuming only acoustic-phonon scattering the charge transport properties were calculated at 300 K. From this model, a carrier concentration of 1.18 × 10 18 cm -3 and a Hall factor of 1.18 were calculated. The low mobility of charge carriers, 19.11 cm²/V·s, and the high effective mass of the electrons, 0.66 m ₀, caused a high resistivity value of 2.75 × 10 -3 Ω·m. The calculated Lorenz factor was 1.50 × 10 -8 V²/K², which represents a decrease of 38% over the degenerate limit value (2.44 × 10 -8 V²/K²).

  3. HuD-mediated distinct BDNF regulatory pathways promote regeneration after nerve injury.

    Science.gov (United States)

    Sanna, Maria Domenica; Ghelardini, Carla; Galeotti, Nicoletta

    2017-03-15

    Up-regulation of brain-derived neurotrophic factor (BDNF) synthesis is an important mechanism of peripheral nerve regeneration after injury. However, the cellular and molecular mechanisms underlying this process are not fully understood. This study examines the role of BDNF in the spared nerve injury (SNI) mice model. Protein expression and cellular localization were investigated in the dorsal root ganglia (DRG) and spinal cord by western blotting and immunofluorescence experiments respectively. BDNF protein was markedly increased 3 and 7days post-injury in the spinal cord and DRG. Following nerve injury sensory neurons produce molecules to promote regeneration, such as growth-associated protein 43 (GAP-43) and cytoskeletal proteins. Our results show that the expression of GAP-43 was increased in the DRG and spinal cord while, an increased of p-NFH content was detected in the spinal cord, with no modification in the DRG. Both events were counteracted by the administration of an anti-BDNF antibody. In DRG of SNI mice we also detected an increase of HuD expression, a RNA-binding protein known to stabilize BDNF and GAP-43 mRNA. Silencing of HuD prevented the nerve injury-induced BDNF and GAP-43 enhanced expression in the DRG. HuD-mediated BDNF synthesis in the primary sensory neurons, is followed by an anterograde transport of the neurotrophin to the central terminals of the primary afferents in the spinal dorsal horn, to modulate GAP-43 and NFH activation. Our data suggest that BDNF, GAP-43 and p-NFH proteins increase are linked events required for the enhanced regeneration after nerve injury. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. BDNF Val66Met polymorphism and serum concentrations of BDNF with smoking in Thai males.

    Science.gov (United States)

    Suriyaprom, K; Tungtrongchitr, R; Thawnashom, K; Pimainog, Y

    2013-10-24

    Many studies have suggested that brain-derived neurotrophic factor (BDNF) is involved in the reward system of addiction, and that nicotine may induce alterations in BDNF gene expression and its protein level within the mesocorticolimbic system. We investigated the BDNF levels and biochemical-hematological parameters of smoker and non-smoker groups, and examined the association of the Val66Met BDNF gene polymorphism with BDNF serum levels and cigarette smoking. The study sample comprised 311 Thai volunteers (200 smokers; 111 non-smokers). The levels of serum BDNF and biochemical-hematological parameters were determined. The Val66Met BDNF polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism technique. The smoker group had significantly higher serum BDNF levels than the non-smoker group (8.3 vs 6.5 ng/mL, P smoked, and thiocyanate level (P smoking status of the Thai males in this study. Cigarette smoking may be one factor that determines the serum BDNF level, but the BDNF Val66Met polymorphism probably does not influence susceptibility to smoking among Thai males.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

    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 2 -molecules are found to significantly increase electrical conductance while the effect of 7-5-5-7 defects is practically annulled by chemisorbed O 2 -molecules. In metallic (5, 5) SWCNTs, both O 2 adsorbates and 7-5-5-7 defects are found to have a relatively small effect on electrical conductance of these nanotubes

  6. Irradiation defects in the A-15 compounds V3Si and Nb3Ge: effects on superconducting and transport properties

    International Nuclear Information System (INIS)

    Rullier-Albenque, F.

    1984-11-01

    In the first part the mechanisms of atomic displacements under electron irradiation in these diatomic ordered solids are studied. In the case of superconducting alloys, simultaneous measurements of electrical resistivity at 20 K and critical temperature allow to distinguish the influence of point defects created in each sub-lattice and antisite defects. The threshold energies have been determined. In the case of V 3 Si, Frenkel pairs have been characterized by their specific resistivities and the decrease of Tsub(c) by vanadium vacancies. The Tsub(c) results obtained on V 3 Si also reveal the existence of a threshold electron energy to produce antisite defects. The second part is a comparative study of irradiation effects in Nb 3 Ge with very different kinds of projectiles: 2.5 MeV electrons, fast neutrons or 100 MeV heavy ions (uranium fission fragments). For these three types of irradiation, resistivity and critical temperature damage can be described in terms of point defects: Frenkel pairs and antisite defects. In the third part we have studied the influence of 2.5 MeV electron or fission fragment-irradiation on the resistivity versus temperature curves of Nb 3 Ge. For both projectiles, negative temperature coefficients of resistivity drho)/dT, were measured and correlated with resistivity at 280 K and 25 K. These anomalous transport properties are related to an electron localization process assisted by electron-phonon and electron-electron interaction [fr

  7. Effect of Native Defects on Transport Properties in Non-Stoichiometric CoSb3

    Directory of Open Access Journals (Sweden)

    Paula R. Realyvázquez-Guevara

    2017-03-01

    Full Text Available The effect of native defects originated by a non-stoichiometric variation of composition in CoSb3 on I-V curves and Hall effect was investigated. Hysteretic and a non-linear behavior of the  I-V curves at cryogenic temperatures were observed; the non-linear behavior originated from the Poole-Frenkel effect, a field-dependent ionization mechanism that lowers Coulomb barriers and increases emission of charge carriers, and the hysteresis was attributed to the drastic decrease of specific heat which produces Joule heating at cryogenic temperatures. CoSb3 is a narrow gap semiconductor and slight variation in the synthesis process can lead to either n- or p-type conduction. The Sb-deficient CoSb3 presented an n-type conduction. Using a single parabolic model and assuming only acoustic-phonon scattering the charge transport properties were calculated at 300 K. From this model, a carrier concentration of 1.18 × 1018 cm−3 and a Hall factor of 1.18 were calculated. The low mobility of charge carriers, 19.11 cm2/V·s, and the high effective mass of the electrons, 0.66 m0, caused a high resistivity value of 2.75 × 10−3 Ω·m. The calculated Lorenz factor was 1.50 × 10−8 V2/K2, which represents a decrease of 38% over the degenerate limit value (2.44 × 10−8 V2/K2.

  8. Effect of Native Defects on Transport Properties in Non-Stoichiometric CoSb3

    Science.gov (United States)

    Realyvázquez-Guevara, Paula R.; Rivera-Gómez, Francisco J.; Faudoa-Arzate, Alejandro; Botello-Zubiate,  María E.; Sáenz-Hernández, Renee J.; Santillán-Rodríguez, Carlos R.; Matutes-Aquino, José A.

    2017-01-01

    The effect of native defects originated by a non-stoichiometric variation of composition in CoSb3 on I-V curves and Hall effect was investigated. Hysteretic and a non-linear behavior of the  I-V curves at cryogenic temperatures were observed; the non-linear behavior originated from the Poole-Frenkel effect, a field-dependent ionization mechanism that lowers Coulomb barriers and increases emission of charge carriers, and the hysteresis was attributed to the drastic decrease of specific heat which produces Joule heating at cryogenic temperatures. CoSb3 is a narrow gap semiconductor and slight variation in the synthesis process can lead to either n- or p-type conduction. The Sb-deficient CoSb3 presented an n-type conduction. Using a single parabolic model and assuming only acoustic-phonon scattering the charge transport properties were calculated at 300 K. From this model, a carrier concentration of 1.18 × 1018 cm−3 and a Hall factor of 1.18 were calculated. The low mobility of charge carriers, 19.11 cm2/V·s, and the high effective mass of the electrons, 0.66 m0, caused a high resistivity value of 2.75 × 10−3 Ω·m. The calculated Lorenz factor was 1.50 × 10−8 V2/K2, which represents a decrease of 38% over the degenerate limit value (2.44 × 10−8 V2/K2). PMID:28772648

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

    International Nuclear Information System (INIS)

    Liscum, L.; Ruggiero, R.M.; Faust, J.R.

    1989-01-01

    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

  10. Are BDNF and glucocorticoid activities calibrated?

    Science.gov (United States)

    Jeanneteau, Freddy; Chao, Moses V.

    2012-01-01

    One hypothesis to account for the onset and severity of neurological disorders is the loss of trophic support. Indeed, changes in the levels and activities of brain-derived neurotrophic factor (BDNF) occur in numerous neurodegenerative and neuropsychiatric diseases. A deficit promotes vulnerability whereas a gain of function facilitates recovery by enhancing survival, synapse formation and synaptic plasticity. Implementation of ‘BDNF therapies’, however, faces numerous methodological and pharmacokinetic issues. Identifying BDNF mimetics that activate the BDNF receptor or downstream targets of BDNF signaling represent an alternative approach. One mechanism that shows great promise is to study the interplay of BDNF and glucocorticoid hormones, a major class of natural steroid secreted during stress reactions and in synchrony with circadian rhythms. While small amounts of glucocorticoids support normal brain function, excess stimulation by these steroid hormones precipitate stress-related affective disorders. To date, however, because of the paucity of knowledge of underlying cellular mechanisms, deleterious effects of glucocorticoids are not prevented following extreme stress. In the present review, we will discuss the complementary roles share by BDNF and glucocorticoids in synaptic plasticity, and delineate possible signaling mechanisms mediating these effects. PMID:23022538

  11. 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…

  12. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Effect of defects on the small polaron formation and transport properties of hematite from first-principles calculations.

    Science.gov (United States)

    Smart, Tyler J; Ping, Yuan

    2017-10-04

    Hematite (α-Fe 2 O 3 ) is a promising candidate as a photoanode material for solar-to-fuel conversion due to its favorable band gap for visible light absorption, its stability in an aqueous environment and its relatively low cost in comparison to other prospective materials. However, the small polaron transport nature in α-Fe 2 O 3 results in low carrier mobility and conductivity, significantly lowering its efficiency from the theoretical limit. Experimentally, it has been found that the incorporation of oxygen vacancies and other dopants, such as Sn, into the material appreciably enhances its photo-to-current efficiency. Yet no quantitative explanation has been provided to understand the role of oxygen vacancy or Sn-doping in hematite. We employed density functional theory to probe the small polaron formation in oxygen deficient hematite, N-doped as well as Sn-doped hematite. We computed the charged defect formation energies, the small polaron formation energy and hopping activation energies to understand the effect of defects on carrier concentration and mobility. This work provides us with a fundamental understanding regarding the role of defects on small polaron formation and transport properties in hematite, offering key insights into the design of new dopants to further improve the efficiency of transition metal oxides for solar-to-fuel conversion.

  14. 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

    2009-02-01

    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-aminophenoxyethane-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.

  15. BDNF Val66Met homozygosity does not influence plasma BDNF levels in healthy human subjects.

    Science.gov (United States)

    Luykx, Jurjen J; Boks, Marco P M; Breetvelt, Elemi J; Aukes, Maartje F; Strengman, Eric; da Pozzo, Eleonora; Dell'osso, Liliana; Marazziti, Donatella; van Leeuwen, Annelies; Vreeker, Annabel; Abramovic, Lucija; Martini, Claudia; Numans, Mattijs E; Kahn, René S; Ophoff, Roel A

    2013-06-03

    A putative pathway by which the BDNF Val66Met polymorphism (rs6265) leads to aberrant phenotypes is its influence on plasma BDNF. Research into the impact of rs6265 on plasma BDNF has given rise to conflicting results. Moreover, most such studies have compared Met-carriers with Val-homozygous subjects. We therefore genotyped subjects from a population-based cohort (the Utrecht Health Project, N=2743) and assessed whether plasma BDNF differs between rs6265 homozygous groups. We maximized the number of Met-homozygous subjects in whom we measured plasma BDNF, resulting in plasma BDNF being available for 19 Met-homozygous and 42 matched Val-homozygous subjects. Mean concentrations (S.D.) were 1963.1 (750.1) and 2133.2 pg/ml (1164.3) for the Val/Val and Met/Met groups, respectively. Using ANOVA, no differences in plasma BDNF between the two groups were detected. In conclusion, these results add to a growing body of evidence indicating that allelic variation at rs6265 does not have medium to large effects on plasma BDNF concentrations. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Non-equilibrium temperatures and heat transport in nanosystems with defects, described by a tensorial internal variable

    Directory of Open Access Journals (Sweden)

    Restuccia Liliana

    2016-06-01

    Full Text Available The paper deals with the meaning of non-equilibrium temperatures in nanosystems with an internal variable, describing defects inside them, and implications on heat transport. In equilibrium all definitions of temperature lead to the same value, but in nonequilibrium steady states they lead to different values, giving information on different degrees of freedom. We discuss the caloric and entropic non-equilibrium temperatures and the relations among them, in defective nanosystems (crystals with dislocations or porous channels, carbon nanotubes in a solid matrix and so on, crossed by an external energy flux. Here, we present a model for nanocrystals with dislocation defects submitted to an external energy flux. The dislocations may have a strong influence on the effective thermal conductivity, and their own dynamics may be coupled in relevant way to the heat flux dynamics. In the linear case the constitutive relations, the rate equations for the internal variable and the heat flux are worked out and a generalized telegraphic heat equation is derived in the anisotropic and isotropic case, describing the thermal disturbances with finite velocity.

  17. 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.

  18. "Multiscale Capabilities for Exploring Transport Phenomena in Batteries": Ab Initio Calculations on Defective LiFePO4

    Energy Technology Data Exchange (ETDEWEB)

    Kanai, Yosuke [Univ. of North Carolina, Chapel Hill, NC (United States); Tang, M [Univ. of North Carolina, Chapel Hill, NC (United States); Wood, B C [Univ. of North Carolina, Chapel Hill, NC (United States)

    2013-10-25

    We have began the project “Multiscale Capability for Exploring Transport Phenomena in Battery”, which is sponsored by Laboratory Directed Research and Development Program at Lawrence Livermore National Laboratory in February 2012 as the subcontract was approved. We have been performing first-principles quantum-mechanical calculations to first establish the general modeling framework. It was found that it is essential to employ advanced Density Functional Theory (DFT) calculations with Hubbard U correction, in order to describe the battery material, in particular, LiFePO4 (Figure 1). The presence of localized d-electrons at Fe ion sites requires the better treatment of non-local correlation beyond that of standard DFT. As our aim was to first identify and investigate key transport/reaction mechanisms affecting the performance of Lithium-ion based batteries, we have began out work by characterizing the standard structures and how the defects influence the important electronic structure.

  19. 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

  20. BDNF control of adult SVZ neurogenesis.

    Science.gov (United States)

    Bath, Kevin G; Akins, Michael R; Lee, Francis S

    2012-09-01

    The sensory processing of odorants is a dynamic process that requires plasticity at multiple levels. In the olfactory bulb (OB), inhibitory interneurons undergo lifelong replacement through a process known as adult neurogenesis. These newly born cells are incorporated in a learning-dependent fashion, a process which has led some to suggest this as a primary mechanism through which the OB retains a high degree of plasticity throughout life. A continued focus of researchers in this field has been to understand the molecular mechanisms controlling adult subventricular zone (SVZ) neurogenesis and the innate functional role of these cells. Brain-derived neurotrophic factor (BDNF) has been identified as a strong candidate molecule regulating adult OB neurogenesis. We review what is known regarding the functional role of newly born cells, highlight the role of BDNF in this process, and describe preliminary findings from our lab implicating BDNF in the process of selecting of newly born cells for survival. Copyright © 2011 Wiley Periodicals, Inc.

  1. 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

  2. Effect of Native Defects on Transport Properties in Non-Stoichiometric CoSb3

    OpenAIRE

    Paula R. Realyvázquez-Guevara; Francisco J. Rivera-Gómez; Alejandro Faudoa-Arzate; María E. Botello-Zubiate; Renee J. Sáenz-Hernández; Carlos R. Santillán-Rodríguez; José A. Matutes-Aquino

    2017-01-01

    The effect of native defects originated by a non-stoichiometric variation of composition in CoSb3 on I-V curves and Hall effect was investigated. Hysteretic and a non-linear behavior of the ?I-V curves at cryogenic temperatures were observed; the non-linear behavior originated from the Poole-Frenkel effect, a field-dependent ionization mechanism that lowers Coulomb barriers and increases emission of charge carriers, and the hysteresis was attributed to the drastic decrease of specific heat wh...

  3. Transport of spin-orbit coupled Bose-Einstein condensates in lattice with defects

    Science.gov (United States)

    Zhu, Kun-Qiang; Yu, Zi-Fa; Xue, Ju-Kui

    2017-07-01

    We theoretically investigate the propagation properties of spin-orbit (SO) coupled Bose-Einstein condensate in an optical lattices with defects. By using the tight-binding and two-mode ansatz approximation, we find that the coupled effects of SO-coupling, Raman coupling, Zeeman field and atomic interactions can control the superfluidity of the system. Particularly, there exists a critical scattering length for crossing from a normal regime to a superfluid regime. The critical scattering length for supporting the superfluidity strongly depends on the defect type, SO-coupling, Raman coupling, Zeeman field and quasimomentum of the plane waves. The SO-coupling and quasimomentum make the system more easily entering into the superfluid regime, while the pure Raman coupling and pure Zeeman field inhibit the system entering into the superfluid regime. Interestingly, the coupled effect between Raman coupling and Zeeman field can both enhance and suppress the system entering into the superfluid regime. This engineering provides a possible means for studying the propagation properties and the corresponding dynamics of two-species SO-coupled BECs in disordered optical lattice.

  4. Anemia of the Belgrade rat: evidence for defective membrane transport of iron

    Energy Technology Data Exchange (ETDEWEB)

    Bowen, B.J.; Morgan, E.H.

    1987-07-01

    The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with /sup 59/Fe and /sup 125/I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect.

  5. Anisotropic thermal transport property of defect-free GaN

    International Nuclear Information System (INIS)

    Ju, Wenjing; Zhou, Zhongyuan; Wei, Zhiyong

    2016-01-01

    Non-equilibrium molecular dynamics (MD) simulation is performed to calculate the thermal conductivity of defect-free GaN along three high-symmetry directions. It is found that the thermal conductivity along [001] direction is about 25% higher than that along [100] or [120] direction. The calculated phonon dispersion relation and iso-energy surface from lattice dynamics show that the difference of the sound speeds among the three high-symmetry directions is quite small for the same mode. However, the variation of phonon irradiation with direction is qualitatively consistent with that of the calculated thermal conductivity. Our results indicate that the anisotropic thermal conductivity may partly result from the phonons in the low-symmetry region of the first Brillouin zone due to phonon focus effects, even though the elastic properties along the three high-symmetry directions are nearly isotropic. Thus, the phonon irradiation is able to better describe the property of thermal conductivity as compared to the commonly used phonon dispersion relation. The present investigations uncover the physical origin of the anisotropic thermal conductivity in defect-free GaN, which would provide an important guide for optimizing the thermal management of GaN-based device.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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 CdCl 2 (2.5 or 5.0 mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl 2 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 CdCl 2 . Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl 2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl 2 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. - Highlights: • Maternal Cd exposure during organogenesis causes NTDs and FGR. • Maternal Cd exposure during organogenesis impairs placental development. • Cd disturbs transport of folate by down-regulating placental folate transporters.

  7. Arginine supplementation in four patients with X-linked creatine transporter defect

    NARCIS (Netherlands)

    Fons, C.; Sempere, A.; Arias, A.; Lopez-Sala, A.; Poo, P.; Pineda, M.; Mas, A.; Vilaseca, M.A.; Salomons, G.S.; Ribes, A.; Artuch, R.; Campistol, J.

    2008-01-01

    Background: Treatment with oral creatine monohydrate has not shown efficacy in patients with creatine transporter deficiency (CRTR-D). Another therapeutic option proposed is L-arginine, the substrate for the enzyme L-arginine:glycine amidinotransferase (AGAT). We evaluate clinical characteristics

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

    International Nuclear Information System (INIS)

    Hersant, D.

    1991-01-01

    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

  9. Effect of thermal friction on the generation and transport of interstitial defects in irradiated metals

    CERN Document Server

    Dudarev, S L

    2002-01-01

    Generation of interstitial and vacancy defects under 14.1 MeV neutron irradiation is expected to drive the evolution of microstructure of materials in a future fusion power station. We investigate effects of thermal friction associated with the interaction between mobile clusters of interstitial atoms produced in collision cascades and phonon excitations. Phonons give rise to the random Brownian motion of clusters in the crystal lattice. Phonon excitations are also responsible for the dissipation of energy of rapidly moving clusters formed at the periphery of collision cascades. We investigate how the coefficient of thermal friction depends on the structure of clusters. We also discuss implications of our findings for understanding the origin of higher resistance of bcc metals to irradiation and the connection between this phenomenon and the long-range effect observed in experiments on ion implantation.

  10. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. BDNF: An Oncogene or Tumor Suppressor?

    Science.gov (United States)

    Radin, Daniel P; Patel, Parth

    2017-08-01

    Neurotrophins are a family of growth factors that are vital to the proper development of the central nervous system. Their effects on cells are governed by the expression and activation of the tyrosine kinase receptors TrkA, TrkB and TrkC. TrkB has been immensely implicated in mediating neuronal migration, development and differentiation. It has also been shown to protect several neuronal cell types from an array of cytotoxic stressors after activation by its conjugate ligand brain-derived neurotrophic factor (BDNF). Over the past two decades, it has been shown that TrkB and BDNF are up-regulated in many types of cancers, conferring aggressive phenotypes underpinned by their resistance to several standard chemotherapeutic agents. This resistance to chemotherapy is modulated by the downstream targets of the TrkB receptor which include the well-characterized PI3K /Akt growth pathway, a hallmark of uncontrolled cancer cell growth and proliferation. Pre-clinical efforts to develop inhibitors of this receptor are promising, and such inhibitors also seem to sensitize cancer cells to standard chemotherapies. However, new evidence suggests that BDNF overexpression in the hypothalamus has immunoaugmenting properties, eliciting an increased anti-tumor immune response and reducing the activity of several proteins that would normally confer resistance to chemotherapeutic agents. In the current work, we provide a global analysis of the physiological consequences of TrkB receptor activation in vitro and discuss the dynamic consequences of TrkB activation in vivo. Finally, we propose a clinically-feasible option for increasing BDNF expression in the hypothalamus to more readily utilize the oncolytic effects of BDNF. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Photoelectrical properties of TlBr related to ionic transport and presence of defects

    Energy Technology Data Exchange (ETDEWEB)

    Kazukauskas, Vaidotas [Semiconductor Physics Department and Institute of Materials Science and Applied Research, Vilnius University, Sauletekio al. 9, bldg. 3, LT-10222 Vilnius (Lithuania)], E-mail: vaidotas.kazukauskas@ff.vu.lt; Ziminskij, Andzej; Vaitkus, Juozas-Vidmantis [Semiconductor Physics Department and Institute of Materials Science and Applied Research, Vilnius University, Sauletekio al. 9, bldg. 3, LT-10222 Vilnius (Lithuania); Gostilo, Vladimir; Shorohov, Mihail [Bruker Baltic, Ganibu dambis 26, P.O.Box 33, LV-1005 Riga (Latvia)

    2009-08-01

    Photoelectrical and current transient properties of TlBr were investigated in the temperature region from -20 up to +20 deg. C, in which effect of the ionic conductivity changes significantly. Non-monotonous conductivity change with temperature was identified, demonstrating mobility-related maximum superimposed on a band-to-band generation conductivity growth. This maximum could be caused by the recharge of the scattering centre at about 1.65 eV. Presence of such centre was confirmed by the photocurrent spectra. From spectral dependencies defect-related transitions at 0.55; 0.83, 1.1; 1.32 and 1.65 eV were identified, being dependent on sample prehistory, i.e., its excitation by light and/or voltage. The transient photocurrent kinetics have demonstrated a complex behaviour that could be explained by the combined influence of electron generation/recombination processes superimposed upon the effect of ionic conductivity. The results indicate that ionic conductivity can take place also at -20 deg. C, though its influence is less because of the thermally activated character.

  13. Intrinsic and extrinsic point-defects in vapor transport grown ZnO bulk crystals

    International Nuclear Information System (INIS)

    Pfisterer, D.; Hofmann, D.M.; Sann, J.; Meyer, B.K.; Tena-Zaera, R.; Munoz-Sanjose, V.; Frank, Th.; Pensl, G.

    2006-01-01

    Vapor transport grown ZnO bulk crystals were characterized by electrical, optical and magnetic resonance spectroscopy. The experiments show that the residual carrier concentration is caused by residual H, Al, Ga, and oxygen vacancies in the material. Annealing the samples in O 2 at about 1000 o C (2 atm, 20 h) reduces the H and V O donor concentration by typical one order of magnitude. The photoluminescence and DLTS results suggest a correlation between the broad unstructured emission at 2.45 eV (green band) and a donor level 530 meV below the conduction band (E4)

  14. Intrinsic and extrinsic point-defects in vapor transport grown ZnO bulk crystals

    Energy Technology Data Exchange (ETDEWEB)

    Pfisterer, D. [I. Physikalisches Institut, Justus-Liebig-Universitaet Giessen, Heinrich-Buff-Ring 16, Giessen D-35392 (Germany); Hofmann, D.M. [I. Physikalisches Institut, Justus-Liebig-Universitaet Giessen, Heinrich-Buff-Ring 16, Giessen D-35392 (Germany)]. E-mail: detlev.m.hofmann@exp1.physik.uni-giessen.de; Sann, J. [I. Physikalisches Institut, Justus-Liebig-Universitaet Giessen, Heinrich-Buff-Ring 16, Giessen D-35392 (Germany); Meyer, B.K. [I. Physikalisches Institut, Justus-Liebig-Universitaet Giessen, Heinrich-Buff-Ring 16, Giessen D-35392 (Germany); Tena-Zaera, R. [Dept. Fisica Aplicada I Electromagnetisme, Universitat de Valencia, C/Dr. Moliner 50, Burjassot 46100 (Spain); Munoz-Sanjose, V. [Dept. Fisica Aplicada I Electromagnetisme, Universitat de Valencia, C/Dr. Moliner 50, Burjassot 46100 (Spain); Frank, Th. [Institut fuer angewandte Physik, Universitaet Erlangen-Nuernberg, Staudtstr. 7/Gebaeude A3, Erlangen D-91058 (Germany); Pensl, G. [Institut fuer angewandte Physik, Universitaet Erlangen-Nuernberg, Staudtstr. 7/Gebaeude A3, Erlangen D-91058 (Germany)

    2006-04-01

    Vapor transport grown ZnO bulk crystals were characterized by electrical, optical and magnetic resonance spectroscopy. The experiments show that the residual carrier concentration is caused by residual H, Al, Ga, and oxygen vacancies in the material. Annealing the samples in O{sub 2} at about 1000 {sup o}C (2 atm, 20 h) reduces the H and V{sub O} donor concentration by typical one order of magnitude. The photoluminescence and DLTS results suggest a correlation between the broad unstructured emission at 2.45 eV (green band) and a donor level 530 meV below the conduction band (E4)

  15. Study of point defects in non crystalline alloys by high temperature mass transport experiments

    International Nuclear Information System (INIS)

    Limoge, Y.

    1986-09-01

    We present in this communication the results of new experiments designed to study the mass transport mechanism in non-crystalline metallic alloys. They are based on the isothermal measurement of the crystallization kinetics, either without constraint or under electron irradiation or hydrostatic pressure. These experiments show that in the alloys studied, (FeNi) 8 (Pb) 2 and Ni 6 Nb 4 ), irradiation enhances the diffusion on the one hand, and on the other that there exist an activation volume for diffusion, of the order of one atomic volume. We discuss then the atomic model of diffusion needed to explain our results

  16. 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.

  17. Effect of nonmagnetic defects on superconducting and transport properties of Ba(Fe1- x Co x As)2 high- T c superconductors

    Science.gov (United States)

    Blokhin, I. S.; Gavrilkin, S. Yu.; Gorshunov, B. P.; Dravin, V. A.; Zhukova, E. S.; Ivanenko, O. M.; Aida, K.; Krasnosvobodtsev, S. I.; Kurt, F.; Mitsen, K. V.; Tsvetkov, A. Yu.

    2015-11-01

    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 T c 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.

  18. High Performance Nano-Crystalline Oxide Fuel Cell Materials. Defects, Structures, Interfaces, Transport, and Electrochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Barnett, Scott [Northwestern Univ., Evanston, IL (United States); Poeppelmeier, Ken [Northwestern Univ., Evanston, IL (United States); Mason, Tom [Northwestern Univ., Evanston, IL (United States); Marks, Lawrence [Northwestern Univ., Evanston, IL (United States); Voorhees, Peter [Northwestern Univ., Evanston, IL (United States)

    2016-09-07

    This project addresses fundamental materials challenges in solid oxide electrochemical cells, devices that have a broad range of important energy applications. Although nano-scale mixed ionically and electronically conducting (MIEC) materials provide an important opportunity to improve performance and reduce device operating temperature, durability issues threaten to limit their utility and have remained largely unexplored. Our work has focused on both (1) understanding the fundamental processes related to oxygen transport and surface-vapor reactions in nano-scale MIEC materials, and (2) determining and understanding the key factors that control their long-term stability. Furthermore, materials stability has been explored under the “extreme” conditions encountered in many solid oxide cell applications, i.e, very high or very low effective oxygen pressures, and high current density.

  19. Charge carrier transport in defective reduced graphene oxide as quantum dots and nanoplatelets in multilayer films

    Science.gov (United States)

    Jimenez, Mawin J. M.; Oliveira, Rafael F.; Almeida, Tiago P.; Hensel Ferreira, Rafael C.; Bufon, Carlos Cesar B.; Rodrigues, Varlei; Pereira-da-Silva, Marcelo A.; Gobbi, Ângelo L.; Piazzetta, Maria H. O.; Riul, Antonio, Jr.

    2017-12-01

    Graphene is a breakthrough 2D material due to its unique mechanical, electrical, and thermal properties, with considerable responsiveness in real applications. However, the coverage of large areas with pristine graphene is a challenge and graphene derivatives have been alternatively exploited to produce hybrid and composite materials that allow for new developments, considering also the handling of large areas using distinct methodologies. For electronic applications there is significant interest in the investigation of the electrical properties of graphene derivatives and related composites to determine whether the characteristic 2D charge transport of pristine graphene is preserved. Here, we report a systematic study of the charge transport mechanisms of reduced graphene oxide chemically functionalized with sodium polystyrene sulfonate (PSS), named as GPSS. GPSS was produced either as quantum dots (QDs) or nanoplatelets (NPLs), being further nanostructured with poly(diallyldimethylammonium chloride) through the layer-by-layer (LbL) assembly to produce graphene nanocomposites with molecular level control. Current-voltage (I-V) measurements indicated a meticulous growth of the LbL nanostructures onto gold interdigitated electrodes (IDEs), with a space-charge-limited current dominated by a Mott-variable range hopping mechanism. A 2D intra-planar conduction within the GPSS nanostructure was observed, which resulted in effective charge carrier mobility (μ) of 4.7 cm2 V-1 s-1 for the QDs and 34.7 cm2 V-1 s-1 for the NPLs. The LbL assemblies together with the dimension of the materials (QDs or NPLs) were favorably used for the fine tuning and control of the charge carrier mobility inside the LbL nanostructures. Such 2D charge conduction mechanism and high μ values inside an interlocked multilayered assembly containing graphene-based nanocomposites are of great interest for organic devices and functionalization of interfaces.

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

    International Nuclear Information System (INIS)

    Li, Xin-Mei; Long, Meng-Qiu; Cui, Li-Ling; Xiao, Jin; Zhang, Xiao-Jiao; Zhang, Dan; Xu, Hui

    2014-01-01

    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 (MoS 2 ) 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 MoS 2 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 MoS 2 nanoribbons. • The effects of V-shaped edge defect and H-saturation. • The effects of spin-filter and negative differential resistance can be observed

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

    NARCIS (Netherlands)

    Gunkel, F.; Wicklein, S.; Hoffmann-Eifert, S.; Meuffels, P.; Brinks, Peter; Huijben, Mark; 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

  2. 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...... explored whether BDNF plays a role in human glucose metabolism. Subjects and methods  We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic...... 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...

  3. Modeling Huntington disease in Drosophila: Insights into axonal transport defects and modifiers of toxicity.

    Science.gov (United States)

    Krench, Megan; Littleton, J Troy

    2013-01-01

    Huntington disease (HD) is an inherited neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in the huntingtin (Htt) gene. Despite years of research, there is no treatment that extends life for patients with the disorder. Similarly, little is known about which cellular pathways that are altered by pathogenic Huntingtin (Htt) protein expression are correlated with neuronal loss. As part of a longstanding effort to gain insights into HD pathology, we have been studying the protein in the context of the fruitfly Drosophila melanogaster. We generated transgenic HD models in Drosophila by engineering flies that carry a 12-exon fragment of the human Htt gene with or without the toxic trinucleotide repeat expansion. We also created variants with a monomeric red fluorescent protein (mRFP) tag fused to Htt that allows in vivo imaging of Htt protein localization and aggregation. While wild-type Htt remains diffuse throughout the cytoplasm of cells, pathogenic Htt forms insoluble aggregates that accumulate in neuronal soma and axons. Aggregates can physically block transport of numerous organelles along the axon. We have also observed that aggregates are formed quickly, within just a few hours of mutant Htt expression. To explore mechanisms of neurodegeneration in our HD model, we performed in vivo and in vitro screens to search for modifiers of viability and pathogenic Htt aggregation. Our results identified several novel candidates for HD therapeutics that can now be tested in mammalian models of HD. Furthermore, these experiments have highlighted the complex relationship between aggregates and toxicity that exists in HD.

  4. Spontaneous sleep-wake cycle and sleep deprivation differently induce Bdnf1, Bdnf4 and Bdnf9a DNA methylation and transcripts levels in the basal forebrain and frontal cortex in rats.

    Science.gov (United States)

    Ventskovska, Olena; Porkka-Heiskanen, Tarja; Karpova, Nina N

    2015-04-01

    Brain-derived neurotrophic factor (Bdnf) regulates neuronal plasticity, slow wave activity and sleep homeostasis. Environmental stimuli control Bdnf expression through epigenetic mechanisms, but there are no data on epigenetic regulation of Bdnf by sleep or sleep deprivation. Here we investigated whether 5-methylcytosine (5mC) DNA modification at Bdnf promoters p1, p4 and p9 influences Bdnf1, Bdnf4 and Bdnf9a expression during the normal inactive phase or after sleep deprivation (SD) (3, 6 and 12 h, end-times being ZT3, ZT6 and ZT12) in rats in two brain areas involved in sleep regulation, the basal forebrain and cortex. We found a daytime variation in cortical Bdnf expression: Bdnf1 expression was highest at ZT6 and Bdnf4 lowest at ZT12. Such variation was not observed in the basal forebrain. Also Bdnf p1 and p9 methylation levels differed only in the cortex, while Bdnf p4 methylation did not vary in either area. Factorial analysis revealed that sleep deprivation significantly induced Bdnf1 and Bdnf4 with the similar pattern for Bdnf9a in both basal forebrain and cortex; 12 h of sleep deprivation decreased 5mC levels at the cortical Bdnf p4 and p9. Regression analysis between the 5mC promoter levels and the corresponding Bdnf transcript expression revealed significant negative correlations for the basal forebrain Bdnf1 and cortical Bdnf9a transcripts in only non-deprived rats, while these correlations were lost after sleep deprivation. Our results suggest that Bdnf transcription during the light phase of undisturbed sleep-wake cycle but not after SD is regulated at least partially by brain site-specific DNA methylation. © 2014 European Sleep Research Society.

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

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    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

  6. Defective enamel and bone development in sodium-dependent citrate transporter (NaCT Slc13a5 deficient mice.

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    Armando R Irizarry

    Full Text Available There has been growing recognition of the essential roles of citrate in biomechanical properties of mineralized tissues, including teeth and bone. However, the sources of citrate in these tissues have not been well defined, and the contribution of citrate to the regulation of odontogenesis and osteogenesis has not been examined. Here, tooth and bone phenotypes were examined in sodium-dependent citrate transporter (NaCT Slc13a5 deficient C57BL/6 mice at 13 and 32 weeks of age. Slc13a5 deficiency led to defective tooth development, characterized by absence of mature enamel, formation of aberrant enamel matrix, and dysplasia and hyperplasia of the enamel organ epithelium that progressed with age. These abnormalities were associated with fragile teeth with a possible predisposition to tooth abscesses. The lack of mature enamel was consistent with amelogenesis imperfecta. Furthermore, Slc13a5 deficiency led to decreased bone mineral density and impaired bone formation in 13-week-old mice but not in older mice. The findings revealed the potentially important role of citrate and Slc13a5 in the development and function of teeth and bone.

  7. Reduced coupling of oxidative phosphorylation in vivo precedes electron transport chain defects due to mild oxidative stress in mice.

    Directory of Open Access Journals (Sweden)

    Michael P Siegel

    Full Text Available Oxidative stress and mitochondrial function are at the core of many degenerative conditions. However, the interaction between oxidative stress and in vivo mitochondrial function is unclear. We used both pharmacological (2 week paraquat (PQ treatment of wild type mice and transgenic (mice lacking Cu, Zn-superoxide dismutase (SOD1(-/- models to test the effect of oxidative stress on in vivo mitochondrial function in skeletal muscle. Magnetic resonance and optical spectroscopy were used to measure mitochondrial ATP and oxygen fluxes and cell energetic state. In both models of oxidative stress, coupling of oxidative phosphorylation was significantly lower (lower P/O at rest in vivo in skeletal muscle and was dose-dependent in the PQ model. Despite this reduction in efficiency, in vivo mitochondrial phosphorylation capacity (ATPmax was maintained in both models, and ex vivo mitochondrial respiration in permeabilized muscle fibers was unchanged following PQ treatment. In association with the reduced P/O, PQ treatment led to a dose-dependent reduction in PCr/ATP ratio and increased phosphorylation of AMPK. These results indicate that oxidative stress uncouples oxidative phosphorylation in vivo and results in energetic stress in the absence of defects in the mitochondrial electron transport chain.

  8. Aging Triggers a Repressive Chromatin State at Bdnf Promoters in Hippocampal Neurons

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    Ernest Palomer

    2016-09-01

    Full Text Available Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR-mediated activation of CaMKII. Decreased NMDAR signaling prevents changes associated with activation at specific Bdnf promoters, including displacement of histone deacetylase 4, recruitment of the histone acetyltransferase CBP, increased H3K27 acetylation, and reduced H3K27 trimethylation. The decrease in NMDA-CaMKII signaling arises from constitutive reduction of synaptic cholesterol that occurs with normal aging. Increasing the levels of neuronal cholesterol in aged neurons in vitro, ex vivo, and in vivo restored NMDA-induced Bdnf expression and chromatin remodeling. Furthermore, pharmacological prevention of age-associated cholesterol reduction rescued signaling and cognitive deficits of aged mice. Thus, reducing hippocampal cholesterol loss may represent a therapeutic approach to reverse cognitive decline during aging.

  9. Reduced naphthylphthalamic acid binding in the tir3 mutant of Arabidopsis is associated with a reduction in polar auxin transport and diverse morphological defects

    Science.gov (United States)

    Ruegger, M.; Dewey, E.; Hobbie, L.; Brown, D.; Bernasconi, P.; Turner, J.; Muday, G.; Estelle, M.

    1997-01-01

    Polar auxin transport plays a key role in the regulation of plant growth and development. To identify genes involved in this process, we have developed a genetic procedure to screen for mutants of Arabidopsis that are altered in their response to auxin transport inhibitors. We recovered a total of 16 independent mutants that defined seven genes, called TRANSPORT INHIBITOR RESPONSE (TIR) genes. Recessive mutations in one of these genes, TIR3, result in altered responses to transport inhibitors, a reduction in polar auxin transport, and a variety of morphological defects that can be ascribed to changes in indole-3-acetic acid distribution. Most dramatically, tir3 seedlings are strongly deficient in lateral root production, a process that is known to depend on polar auxin transport from the shoot into the root. In addition, tir3 plants display a reduction in apical dominance as well as decreased elongation of siliques, pedicels, roots, and the inflorescence. Biochemical studies indicate that tir3 plants have a reduced number of N-1-naphthylphthalamic (NPA) binding sites, suggesting that the TIR3 gene is required for expression, localization, or stabilization of the NPA binding protein (NBP). Alternatively, the TIR3 gene may encode the NBP. Because the tir3 mutants have a substantial defect in NPA binding, their phenotype provides genetic evidence for a role for the NBP in plant growth and development.

  10. Partially Defective Store Operated Calcium Entry and Hem(ITAM Signaling in Platelets of Serotonin Transporter Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Karen Wolf

    Full Text Available Serotonin (5-hydroxytryptamin, 5-HT is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A. Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation.To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke.5-HT transporter knockout mice (5Htt-/- were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke.In 5Htt-/- platelets, 5-HT uptake from the blood was completely abolished and agonist-induced Ca2+ influx through store operated Ca2+ entry (SOCE, integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI and C-type lectin-like receptor 2 (CLEC-2 were reduced. These observed in vitro defects in 5Htt-/- platelets could be normalized by the addition of exogenous 5-HT. Moreover, reduced 5-HT levels in the plasma, an increased bleeding time and the formation of unstable thrombi were observed ex vivo under flow and in vivo in the abdominal aorta and carotid artery of 5Htt-/- mice. Surprisingly, in the transient middle cerebral artery occlusion (tMCAO model of ischemic stroke 5Htt-/- mice showed nearly normal infarct volume and the neurological outcome was comparable to control mice.Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization.

  11. Investigation of transport phenomena and defect formation in pulsed laser keyhole welding of zinc-coated steels

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, J [Department of Mechanical and Engineering Technology, Georgia Southern University, PO Box 8046, Statesboro, GA 30460 (United States); Tsai, H L [Department of Mechanical and Aerospace Engineering, University of Missouri-Rolla, 1870 Miner Circle, Rolla, MO 65409 (United States); Lehnhoff, T F [Department of Mechanical and Aerospace Engineering, University of Missouri-Rolla, 1870 Miner Circle, Rolla, MO 65409 (United States)

    2006-12-21

    Lasers are being used to weld zinc-coated steels due to high welding speed, high aspect ratio, and narrow heat affected zone. However, escape of high-pressure zinc vapour in the welding process can damage the weld pool continuity and cause large voids and serious undercuts in the final welds. In this paper, a mathematical model and the associated numerical techniques have been developed to study the transport phenomena and defect formation mechanisms in pulsed laser keyhole welding of zinc-coated steels. The volume-of-fluid (VOF) method is employed to track free surfaces. The continuum model is used to handle the liquid phase, the solid phase and the mushy zone of the metal. The enthalpy method is employed to account for the latent heat during melting and solidification. The transient heat transfer and melt flow in the weld pool during the keyhole formation and collapse processes are calculated. The escape of zinc vapour through the keyhole and the interaction between zinc vapour and weld pool are studied. Voids in the welds are found to be caused by the combined effects of zinc vapour-melt interactions, keyhole collapse and solidification process. By controlling the laser pulse profile, it is found that the keyhole collapse and solidification process can be delayed, allowing the zinc vapour to escape, which results in the reduction or elimination of voids. The good agreement between the model predictions and the experimental observations indicates that the proposed model lays a solid foundation for future study of laser welding of zinc-coated steels.

  12. Endurance training enhances BDNF release from the human brain

    DEFF Research Database (Denmark)

    Seifert, Thomas; Brassard, Patrice; Wissenberg, Mads

    2010-01-01

    The circulating level of brain-derived neurotrophic factor (BDNF) is reduced in patients with major depression and type-2 diabetes. Because acute exercise increases BDNF production in the hippocampus and cerebral cortex, we hypothesized that endurance training would enhance the release of BDNF from...... the human brain as detected from arterial and internal jugular venous blood samples. In a randomized controlled study, 12 healthy sedentary males carried out 3 mo of endurance training (n = 7) or served as controls (n = 5). Before and after the intervention, blood samples were obtained at rest and during...... exercise. At baseline, the training group (58 + or - 106 ng x 100 g(-1) x min(-1), means + or - SD) and the control group (12 + or - 17 ng x 100 g(-1) x min(-1)) had a similar release of BDNF from the brain at rest. Three months of endurance training enhanced the resting release of BDNF to 206 + or - 108...

  13. Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling.

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    Jillian L Shaw

    Full Text Available Post-mortem brains from Down syndrome (DS and Alzheimer's disease (AD patients show an upregulation of the Down syndrome critical region 1 protein (DSCR1, but its contribution to AD is not known. To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP, which is known to cause AD when duplicated or upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays neurodegeneration and ameliorates axonal transport defects caused by APP overexpression. Live-imaging reveals that Nebula facilitates the transport of synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we show that Nebula upregulation protects against axonal transport defects by restoring calcineurin and GSK-3β signaling altered by APP overexpression, thereby preserving cargo-motor interactions. As impaired transport of essential organelles caused by APP perturbation is thought to be an underlying cause of synaptic failure and neurodegeneration in AD, our findings imply that correcting calcineurin and GSK-3β signaling can prevent APP-induced pathologies. Our data further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the presence of APP upregulation and provides evidence for calcineurin inhibition as a novel target for therapeutic intervention in preventing axonal transport impairments associated with AD.

  14. Conjunctivally Applied BDNF Protects Photoreceptors from Light-Induced Damage.

    Science.gov (United States)

    Cerri, Elisa; Origlia, Nicola; Falsini, Benedetto; Barloscio, Davide; Fabiani, Carlotta; Sansò, Marco; Ottino, Sara; Giovannini, Luca; Domenici, Luciano

    2015-11-01

    To test whether the topical eye treatment with BDNF prevents the effects of continuous light exposure (LE) in the albino rat retina. Two groups of albino rats were used. The first group of rats received an intraocular injection of BDNF (2 μL, 1 μg/μL) before LE, while the second group was treated with one single drop of BDNF (10 μL, 12 μg/μL) dissolved in different types of solutions (physiological solution, the polysaccharide fraction of Tamarind gum, TSP, and sodium carboxy methyl cellulose), at the level of conjunctival fornix before LE. The level of BDNF in the retina and optic nerve was determined by enzyme-linked immunosorbent assay. We recorded the flash electroretinogram (fERG) in dark adapted rats 1 week after LE. At the end of the recording session, the retinas were removed and labeled so that the number of photoreceptors nuclear rows and thickness of the outer nuclear layer was analyzed. Intravitreal injection of BDNF before LE prevented fERG impairment. Different ophthalmic preparations were used for topical eye application; the TSP resulted the most suitable vehicle to increase BDNF level in the retina and optic nerve. Topical eye application with BDNF/TSP before LE partially preserved both fERG response and photoreceptors. Topical eye treatment with BDNF represents a suitable, noninvasive tool to increase the retinal content of BDNF up to a level capable of exerting neuroprotection toward photoreceptors injured by prolonged LE. A collyrium containing BDNF may serve as an effective, clinically translational treatment against retinal degeneration.

  15. 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…

  16. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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    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.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  19. 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.

  20. The Effect of Brain-Derived Neurotrophic Factor on Periodontal Furcation Defects

    Science.gov (United States)

    Jimbo, Ryo; Tovar, Nick; Janal, Malvin N.; Mousa, Ramy; Marin, Charles; Yoo, Daniel; Teixeira, Hellen S.; Anchieta, Rodolfo B.; Bonfante, Estevam A.; Konishi, Akihiro; Takeda, Katsuhiro; Kurihara, Hidemi; Coelho, Paulo G.

    2014-01-01

    This study aimed to observe the regenerative effect of brain-derived neurotrophic factor (BDNF) in a non-human primate furcation defect model. Class II furcation defects were created in the first and second molars of 8 non-human primates to simulate a clinical situation. The defect was filled with either, Group A: BDNF (500 µg/ml) in high-molecular weight-hyaluronic acid (HMW-HA), Group B: BDNF (50 µg/ml) in HMW-HA, Group C: HMW-HA acid only, Group D: empty defect, or Group E: BDNF (500 µg/ml) in saline. The healing status for all groups was observed at different time-points with micro computed tomography. The animals were euthanized after 11 weeks, and the tooth-bone specimens were subjected to histologic processing. The results showed that all groups seemed to successfully regenerate the alveolar buccal bone, however, only Group A regenerated the entire periodontal tissue, i.e., alveolar bone, cementum and periodontal ligament. It is suggested that the use of BDNF in combination with a scaffold such as the hyaluronic acid in periodontal furcation defects may be an effective treatment option. PMID:24454754

  1. DCL2- and RDR6-dependent transitive silencing of SMXL4 and SMXL5 in Arabidopsis dcl4 mutants causes defective phloem transport and carbohydrate over-accumulation.

    Science.gov (United States)

    Wu, Yu-Yi; Hou, Bo-Han; Lee, Wen-Chi; Lu, Shin-Hua; Yang, Chen-Jui; Vaucheret, Hervé; Chen, Ho-Ming

    2017-06-01

    DICER-LIKE (DCL) enzymes process double-stranded RNA into small RNAs that act as regulators of gene expression. Arabidopsis DCL4 and DCL2 each allow the post-transcriptional gene silencing (PTGS) of viruses and transgenes, but primary PTGS-prone DCL4 outcompetes transitive PTGS-prone DCL2 in wild-type plants. This hierarchy likely prevents DCL2 having any detrimental effects on endogenous genes. Indeed, dcl4 mutants exhibit developmental defects and increased sensitivity to genotoxic stress. In this study, the mechanism underlying dcl4 defects was investigated using genetic, biochemical and high-throughput sequencing approaches. We show that the purple phenotype of dcl4 leaves correlates with carbohydrate over-accumulation and defective phloem transport, and depends on the activity of SUPPRESSOR OF GENE SILENCING 3, RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) and DCL2. This phenotype correlates with the downregulation of two genes expressed in the apex and the vasculature, SMAX1-LIKE 4 (SMXL4) and SMXL5, and the accumulation of DCL2- and RDR6-dependent small interfering RNAs derived from these two genes. Supporting a causal effect, smxl4 smxl5 double mutants exhibit leaf pigmentation, enhanced starch accumulation and defective phloem transport, similar to dcl4 plants. Overall, this study elucidates the detrimental action of DCL2 when DCL4 is absent, and indicates that DCL4 outcompeting DCL2 in wild-type plants is crucial to prevent the degradation of endogenous transcripts by DCL2- and RDR6-dependent transitive PTGS. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  2. BDNF genotype modulates resting functional connectivity in children

    Directory of Open Access Journals (Sweden)

    Moriah E Thomason

    2009-11-01

    Full Text Available 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 gene variants and neural resting connectivity in children and adolescents. We observed a reduction in hippocampal and parahippocampal to cortical connectivity in met-allele carriers within each of three resting networks: the default-mode, executive, and paralimbic networks. In contrast, we observed increased connectivity to amygdala, insula and striatal regions in met-carriers, within the paralimbic network. Because the BDNF met-allele has been linked to increased susceptibility to neuropsychiatric disorders, this latter finding of greater connectivity in circuits important for emotion processing may indicate a new neural mechanism through which these gene-related psychiatric differences are manifest. Here we show that the BDNF gene, known to regulate synaptic plasticity and connectivity in the brain, affects functional connectivity at the neural systems level. Additionally, we provide the first demonstration that the spatial topography of multiple high-level resting state networks in healthy children and adolescents is similar to that observed in adults.

  3. BDNF mechanisms in late LTP formation: A synthesis and breakdown.

    Science.gov (United States)

    Panja, Debabrata; Bramham, Clive R

    2014-01-01

    Unraveling the molecular mechanisms governing long-term synaptic plasticity is a key to understanding how the brain stores information in neural circuits and adapts to a changing environment. Brain-derived neurotrophic factor (BDNF) has emerged as a regulator of stable, late phase long-term potentiation (L-LTP) at excitatory glutamatergic synapses in the adult brain. However, the mechanisms by which BDNF triggers L-LTP are controversial. Here, we distill and discuss the latest advances along three main lines: 1) TrkB receptor-coupled translational control underlying dendritic protein synthesis and L-LTP, 2) Mechanisms for BDNF-induced rescue of L-LTP when protein synthesis is blocked, and 3) BDNF-TrkB regulation of actin cytoskeletal dynamics in dendritic spines. Finally, we explore the inter-relationships between BDNF-regulated mechanisms, how these mechanisms contribute to different forms of L-LTP in the hippocampus and dentate gyrus, and outline outstanding issues for future research. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Influence of BDNF Genotype and Exercise on BDNF Serum Levels and VO2 Max after Acute Exercise and Post Training

    Science.gov (United States)

    2017-07-29

    across age and gender groups [12,13,14,15,16]. Exercise-based cognitive augmentation is thought to be mediated by BDNF [17,18]. BDNF is a...memory and decision- making) (termed FAC henceforth) to traditional AFPT (LC). The FAC training incorporated motions from real world actions (e.g...effectively discriminated since the results are consistent above the prior probabilities in a random guess. 17 Distribution A: Approved for public

  5. Exposure to early life stress regulates Bdnf expression in SERT mutant rats in an anatomically selective fashion.

    Science.gov (United States)

    Calabrese, Francesca; van der Doelen, Rick H A; Guidotti, Gianluigi; Racagni, Giorgio; Kozicz, Tamas; Homberg, Judith R; Riva, Marco A

    2015-01-01

    Although the causes of psychiatric disorders are not fully understood, it is well established that mental illness originates from the interaction between genetic and environmental factors. In this regard, compelling evidence demonstrates that depression can be the consequence of altered, and often maladaptive, response to adversities during pre- and early post-natal life. In this study, we investigated the impact of chronic maternal separation (MS) on the expression of the neurotrophin brain-derived neurotrophic factor (BDNF) in serotonin transporter (SERT) knockout rats in the ventral and dorsal hippocampus as well as the ventromedial and dorsomedial prefrontal cortex (PFC). We found that both SERT deletion and the MS led to an overall reduction in Bdnf expression in the ventral hippocampus and the ventromedial PFC, whereas in the dorsal hippocampus and in the dorsomedial PFC, we observed a significant increase in the neurotrophin gene expression after MS exposure, specifically in the heterozygous SERT rats. In summary, we show that the modulation of Bdnf expression in SERT mutant rats exposed to MS reflects the complex functional consequences of this gene-environment interaction with a clear distinction between the ventral and the dorsal subfields of the hippocampus and of the PFC. Early life stress differently affects the expression of Bdnf in an anatomically distinct manner as a function of SERT genotype. Specifically, both SERT deletion and the maternal separation (MS) led to an overall reduction in Bdnf expression in the ventral hippocampus and in the ventromedial prefrontal cortex, whereas in the dorsal hippocampus and in the dorsomedial prefrontal cortex, we observed a significant increase in the neurotrophin gene expression after MS exposure specifically in the heterozygous SERT rats. We think that these findings may provide novel cues for modulating neurotrophin function, which is dys-regulated in several psychiatric conditions. © 2014 International

  6. 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....... Brains from young (5 months old) and old (13 months old) congenital Learned Helplessness rats (cLH), and congenital Non Learned Helplessness rats (cNLH) were immunohistochemically stained for the serotonin transporter and subsequently stereologically quantified for estimating hippocampal serotonin fiber...... 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...

  7. Botanicals as Modulators of Neuroplasticity: Focus on BDNF

    Directory of Open Access Journals (Sweden)

    Enrico Sangiovanni

    2017-01-01

    Full Text Available The involvement of brain-derived neurotrophic factor (BDNF in different central nervous system (CNS diseases suggests that this neurotrophin may represent an interesting and reliable therapeutic target. Accordingly, the search for new compounds, also from natural sources, able to modulate BDNF has been increasingly explored. The present review considers the literature on the effects of botanicals on BDNF. Botanicals considered were Bacopa monnieri (L. Pennell, Coffea arabica L., Crocus sativus L., Eleutherococcus senticosus Maxim., Camellia sinensis (L. Kuntze (green tea, Ginkgo biloba L., Hypericum perforatum L., Olea europaea L. (olive oil, Panax ginseng C.A. Meyer, Rhodiola rosea L., Salvia miltiorrhiza Bunge, Vitis vinifera L., Withania somnifera (L. Dunal, and Perilla frutescens (L. Britton. The effect of the active principles responsible for the efficacy of the extracts is reviewed and discussed as well. The high number of articles published (more than one hundred manuscripts for 14 botanicals supports the growing interest in the use of natural products as BDNF modulators. The studies reported strengthen the hypothesis that botanicals may be considered useful modulators of BDNF in CNS diseases, without high side effects. Further clinical studies are mandatory to confirm botanicals as preventive agents or as useful adjuvant to the pharmacological treatment.

  8. Relationship Between Brain-Derived Neurotrofic Factor (Bdnf) and Sleep on Depression: A Critical Review

    OpenAIRE

    Monteiro, Bárbara C.; Monteiro, Suzana; Candida, Maristela; Adler, Nathalia; Paes, Flavia; Rocha, Nuno; Nardi, Antonio Egidio; Murillo-Rodriguez, Eric; Machado, Sergio

    2017-01-01

    The Brain-Derived Neurotrofic Factor (BDNF) is one of the most important neurotrophins in the brain and it is suggested influences the activity of the serotonergic, noradrenergic and dopaminergic pathways. In the last few years, it has been hypothesized that BDNF level is related with depression and sleep. Several studies show that depressive subjects present low levels of BDNF in the brain. Poor sleep quality is also related with alterations in the BDNF concentration. Some authors argue that...

  9. Birth Defects

    Science.gov (United States)

    A birth defect is a problem that happens while a baby is developing in the mother's body. Most birth defects happen during the first 3 months of ... in the United States is born with a birth defect. A birth defect may affect how the ...

  10. Treatment by oral creatine, L-arginine and L-glycine in six severely affected patients with creatine transporter defect

    NARCIS (Netherlands)

    Valayannopoulos, V.; Boddaert, N.; Chabli, A.; Barbier, V.; Desguerre, I.; Philippe, A.; Afenjar, A.; Mazzuca, M.; Cheillan, D.; Munnich, A.; de Keyzer, Y.; Jakobs, C.A.J.M.; Salomons, G.S.; de Lonlay, P.

    2012-01-01

    Background X-linked cerebral creatine deficiency is caused by the deficiency of the creatine transporter (CTP) encoded by the SLC6A8 gene. Patients and Methods We report here a series of six patients with severe CTP deficiency, four males and two females; clinical presentations include mild to

  11. Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

    Directory of Open Access Journals (Sweden)

    Sandra M. Garraway

    2016-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions.

  12. Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord.

    Science.gov (United States)

    Garraway, Sandra M; Huie, J Russell

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI) influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions.

  13. Polymer-dielectric molecular interactions in defect-free poly(3-hexylthiophene): dependence and consequences of regioregularity on transistor charge transport properties

    Science.gov (United States)

    Nawaz, Ali; Cruz-Cruz, Isidro; Rego, Jessica S.; Koehler, Marlus; Gopinathan, Sreelekha P.; Kumar, Anil; Hümmelgen, Ivo A.

    2017-08-01

    We investigate the molecular interaction of poly(3-hexylthiophene-2,5-diyl) (P3HT) molecules with polar functional groups of the dielectric surface, and its dependence on the regioregularity of P3HT. With this aim, we consider thickness-dependent molecular order of 100% regioregular defect-free P3HT (DF-P3HT) and 93% regioregular P3HT (LT-P3HT), deposited on top of cross-linked poly(vinyl alcohol) (cr-PVA) substrates. Intimate contact of P3HT molecules and cr-PVA surface defects affects the molecular order of P3HT differently, depending on the regioregularity. Consequently, these molecular order changes on the charge transport properties of organic field-effect transistors (OFETs) are investigated using four thicknesses (20, 40, 80 and 120 nm) of P3HT. As compared to other thicknesses, μ sat for 20 nm DF-P3HT OFETs shows further improvement, while the opposite occurs for 20 nm LT-P3HT OFETs. Depending on the regioregularity (and thus the chain orientation), P3HT molecules exhibit a difference in dipole moments. Consequently, the interaction of edge-on or face-on P3HT molecules with cr-PVA surface dipoles has different contributions towards the electrostatic energetic disorder at cr-PVA/P3HT interface. This subtle difference of behavior helps one to understand the huge spread of characteristics of P3HT based transistors found in literature.

  14. A novel BDNF gene promoter directs expression to skeletal muscle

    Directory of Open Access Journals (Sweden)

    Heinrich Gerhard

    2003-06-01

    Full Text Available Abstract Background Cell-specific expression of the gene that encodes brain-derived neurotrophic factor (BDNF is required for the normal development of peripheral sensory neurons and efficient synaptic transmission in the mature central and peripheral nervous system. The control of BDNF gene expression involves multiple tissue and cell-specific promoters that are differentially regulated. The molecular mechanisms that are responsible for tissue and cell-specific expression of these promoters are still incompletely understood. Results The cloning and analysis of three additional zebrafish (Danio rerio BDNF gene exons and two associated promoters, is reported. Among them are two exons that generate a novel tripartite mature transcript. The exons were located on the transcription unit, whose overall organization was determined by cloning, Southern blot hybridization and sequence analysis, and compared with the pufferfish (Fugu rubripes and mammalian BDNF loci, revealing a conserved but more compact organization. Structural and functional analysis of the exons, their adjacent promoters and 5' flanks, showed that they are expressed cell-specifically. The promoter associated with the 5' exon of the tripartite transcript is GC-rich, TATA-less and the 5' flank adjacent to it contains multiple Sp1, Mef2, and AP1 elements. A fusion gene containing the promoter and 1.5 KB of 5' flank is directed exclusively to skeletal muscle of transiently transfected embryos. The second promoter, whose associated 5' exon contains a 25-nucleotide segment of identity with a mammalian BDNF gene exon, was transiently expressed in yolk of the early embryo. RT-PCR analysis of total RNA from whole juvenile fish and adult female skeletal muscle revealed tissue-specific expression of the 5' exons but the novel exon could not be detected even after two rounds of nested PCR. Conclusion The zebrafish BDNF gene is as complex as the mammalian gene yet much more compact. Its exons are

  15. Structure, Defects and Electronic Transport in High-Mobility BaSnO3 Films and Heterostructures

    Science.gov (United States)

    Jalan, Bharat

    Wide bandgap perovskite oxides with high room-temperature conductivities that are structurally compatible with other perovskite materials are of significant current interest as transparent conductors and as active components in high performance power electronics. Such materials must also possess high room-temperature mobility to minimize power consumption and to enable high frequency applications. In this talk, I will focus on the detailed electronic transport study of La-doped BaSnO3 films and heterostructures grown using the hybrid molecular beam epitaxy technique. We will discuss the mobility-limiting scattering mechanisms by calculating temperature-dependent mobility, and Seebeck coefficient using the Boltzmann transport framework and ab initiocalculations. Finally, we will provide pathways to realize high mobility two-dimensional electron gases in BaSnO3 via bandgap engineering approaches. Supported by the NSF and AFOSR YIP.

  16. Distinct roles of prelimbic and infralimbic proBDNF in extinction of conditioned fear.

    Science.gov (United States)

    Sun, Wei; Li, Xiaoliang; An, Lei

    2018-03-15

    Brain-derived neurotrophic factor (BDNF) has been investigated for its positive role in regulation of fear acquisition and memory. The precursor of BDNF, proBDNF, has been identified as different protein from its mature form. The prelimbic (PL) and infralimbic (IL) sub-regions of the medial prefrontal cortex (mPFC) are functionally distinct in fear behavior. However, the role of PL and IL proBDNF in fear memory is unclear. Here, through the infusion of cleavage-resistant proBDNF and its antibody, we identified the dissociable roles of PL and IL proBDNF in fear expression and extinction memory as well as explored proBDNF's potential mechanism of action. The results suggest that the infusion of proBDNF in the IL facilitates induction of fear extinction, while infusion in the PL depresses fear expression. Blocking proBDNF by using its antibody disrupted the acquisition of fear extinction in the IL, but not the PL. Furthermore, proBDNF-induced extinction was sufficient for extinguishing new and older memories, and required NR2B, but not NR2A, -containing NMDA receptors. We also observed extinction-related proBDNF expression increased in the PL and IL during successful fear expression and extinction, respectively. Importantly, enhanced proBDNF was required for maintaining an extinguished behavior. The extinction effects of proBDNF did not involve degrading the original fear memory. Therefore, proBDNF in the IL and PL differentially contribute to the inhibitory control of fear extinction behavior. Our findings provide a strong link between proBDNF activity and deficits in fear extinction, a hallmark of several psychiatric disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Abortive replication of Bombyx mori nucleopolyhedrovirus in Sf9 and High Five cells: Defective nuclear transport of the virions

    International Nuclear Information System (INIS)

    Katou, Yasuhiro; Ikeda, Motoko; Kobayashi, Michihiro

    2006-01-01

    Despite close genetic relationship, Bombyx mori nucleopolyhedrovirus (BmNPV) and Autographa californica multicapsid NPV (AcMNPV) display a distinct host range property. Here, BmNPV replication was examined in Sf9 and High Five cells that were nonproductive for BmNPV infection but supported high titers of AcMNPV replication. Recombinant BmNPV, vBm/gfp/lac, containing bm-ie1 promoter-driven egfp showed that few Sf9 and High Five cells infected with vBm/gfp/lac expressed EGFP, while large proportion of EGFP-expressing cells was observed when transfected with vBm/gfp/lac DNA. Immunocytochemical analysis showed that BmNPV was not imported into the nucleus of these two cell lines, while recombinant BmNPV, vBmΔ64/ac-gp64 possessing AcMNPV gp64 was imported into the nucleus, yielding progeny virions in High Five cells, but not Sf9 cells. These results indicate that the defective nuclear import of infected virions due to insufficient BmNPV GP64 function is involved in the restricted BmNPV replication in Sf9 and High Five cells

  19. 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

    with a 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...... familiar risk of affective disorder and the met allele was associated with a higher whole blood BDNF (p=0.02) and a higher evening cortisol level (p=0.01), but not with awakening cortisol. CONCLUSION: Individuals at high risk of affective disorders and who are carriers of the met allele of the Val66Met...

  20. 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.

  1. Relationship Between Brain-Derived Neurotrofic Factor (Bdnf) and Sleep on Depression: A Critical Review

    Science.gov (United States)

    Monteiro, Bárbara C.; Monteiro, Suzana; Candida, Maristela; Adler, Nathalia; Paes, Flavia; Rocha, Nuno; Nardi, Antonio Egidio; Murillo-Rodriguez, Eric; Machado, Sergio

    2017-01-01

    The Brain-Derived Neurotrofic Factor (BDNF) is one of the most important neurotrophins in the brain and it is suggested influences the activity of the serotonergic, noradrenergic and dopaminergic pathways. In the last few years, it has been hypothesized that BDNF level is related with depression and sleep. Several studies show that depressive subjects present low levels of BDNF in the brain. Poor sleep quality is also related with alterations in the BDNF concentration. Some authors argue that most of the cases show that impaired sleep quality increases the stress and, consequently, the vulnerability to depressive disorders, suggesting that there is a relationship between sleep, depression and BDNF levels. PMID:29299044

  2. 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.

  3. A pqr2 mutant encodes a defective polyamine transporter and is negatively affected by ABA for paraquat resistance in Arabidopsis thaliana.

    Science.gov (United States)

    Dong, Shuchao; Hu, Huizhen; Wang, Youmei; Xu, Zhengdan; Zha, Yi; Cai, Xiwen; Peng, Liangcai; Feng, Shengqiu

    2016-09-01

    Despite the paraquat-resistant mutants that have been reported in plants, this study identified a novel A. thaliana mutant (pqr2) from an XVE inducible activation library based on its resistance to 2 μM paraquat. The pqr2 mutant exhibited a termination mutation in the exon of AT1G31830/PAR1/PQR2, encoded a polyamine uptake transporter AtPUT2/PAR1/PQR2. The PQR2 mutation could largely reduce superoxide accumulation and cell death in the pqr2 plants under paraquat treatment. Moreover, compared with wild type, the pqr2 mutant exhibited much reduced tolerance to putrescine, a classic polyamine compound, which confirmed that PQR2 encoded a defective polyamine transporter. Notably, co-treated with ABA and paraquat, both pqr2 mutant and wild type exhibited a lethal phenotype from seed germination, but the wild type like pqr2 mutant, could remain paraquat-resistance while co-treated with high dosage of Na2WO4, an ABA synthesis inhibitor. Gene expression analysis suggested that ABA signaling should widely regulate paraquat-responsive genes distinctively in wild type and pqr2 mutant. Hence, this study has for the first time reported about ABA negative effect on paraquat-resistance in A. thaliana, providing insight into the ABA signaling involved in the oxidative stress responses induced by paraquat in plants.

  4. 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.

  5. Combined cisplatin and aurora inhibitor treatment increase neuroblastoma cell death but surviving cells overproduce BDNF

    Directory of Open Access Journals (Sweden)

    Alessio Polacchini

    2016-07-01

    Full Text Available Drug-resistance to chemotherapics in aggressive neuroblastoma (NB is characterized by enhanced cell survival mediated by TrkB and its ligand, brain-derived neurotrophic factor (BDNF; thus reduction in BDNF levels represent a promising strategy to overcome drug-resistance, but how chemotherapics regulate BDNF is unknown. Here, cisplatin treatment in SK-N-BE neuroblastoma upregulated multiple BDNF transcripts, except exons 5 and 8 variants. Cisplatin increased BDNF mRNA and protein, and enhanced translation of a firefly reporter gene flanked by BDNF 5′UTR exons 1, 2c, 4 or 6 and 3′UTR-long. To block BDNF translation we focused on aurora kinases inhibitors which are proposed as new chemotherapeutics. NB cell survival after 24 h treatment was 43% with cisplatin, and 22% by cisplatin+aurora kinase inhibitor PHA-680632, while the aurora kinases inhibitor alone was less effective; however the combined treatment induced a paradoxical increase of BDNF in surviving cells with strong translational activation of exon6-3′UTR-long transcript, while translation of BDNF transcripts 1, 2C and 4 was suppressed. In conclusion, combined cisplatin and aurora kinase inhibitor treatment increases cell death, but induces BDNF overproduction in surviving cells through an aurora kinase-independent mechanism.

  6. Antidepressant-Like Effects of Central BDNF Administration in Mice of Antidepressant Sensitive Catalepsy (ASC) Strain.

    Science.gov (United States)

    Tikhonova, Maria; Kulikov, Alexander V

    2012-08-31

    Although numerous data evidence the implication of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression, the potential for BDNF to correct genetically defined depressive-like states is poorly studied. This study was aimed to reveal antidepressant-like effects of BDNF (300 ng, 2×, i.c.v.) on behavior and mRNA expression of genes associated with depression-like state in the brain in mice of antidepressant sensitive catalepsy (ASC) strain characterized by high hereditary predisposition to catalepsy and depressive-like features. Behavioral tests were held on the 7th-16th days after the first (4th-13th after the second) BDNF injection. Results showed that BDNF normalized impaired sexual motivation in the ASC males, and this BDNF effect differed, with advantageous effects, from that of widely used antidepressants. The anticataleptic effect of two BDNF injections was enhanced compared with a single administration. A tendency to decrease the immobility duration in tail-suspension test was observed in BDNF-treated ASC mice. The effects on catalepsy and sexual motivation were specific since BDNF did not alter locomotor and exploratory activity or social interest in the ASC mice. Along with behavioral antidepressant-like effects on the ASC mice, BDNF increased hippocampal mRNA levels of Bdnf and Creb1 (cAMP response element-binding protein gene). BDNF also augmented mRNA levels of Arc gene encoding Arc (Activity-regulated cytoskeleton-associated) protein involved in BDNF-induced processes of neuronal and synaptic plasticity in hippocampus and prefrontal cortex. The data suggest that: [1] BDNF is effective in the treatment of some genetically defined behavioral disturbances; [2] BDNF influences sexually-motivated behavior; [3] Arc mRNA levels may serve as a molecular marker of BDNF physiological activity associated with its long-lasting behavioral effects; [4] ASC mouse strain can be used as a suitable model to study mechanisms of BDNF effects on

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

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Vinberg, Maj; Aznar, Susana

    2008-01-01

    and protected against affective disorder. Whole blood assessed for BDNF concentrations and correlated to risk status, neuroticism, and number of stressful life events. RESULTS: Between the groups, we found no significant difference in whole blood BDNF levels. Women at high-risk for depression who had......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...... experienced three or more recent stressful events (n=26) had decreased whole blood BDNF levels compared to high-risk women with two or less recent stressful events (n=35), 21.6+/-7.0 vs. 18.5+/-4.1 ng/ml, respectively, (p

  8. 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 anxiety-like scores, high self-grooming, impaired prepulse inhibition, and higher susceptibility to seizures when placed in a new empty cage, as compared with wild-type (WT) littermate controls. Control measures of general health, locomotor activity, motor coordination, depression-related behaviors, and sociability did not differ between genotypes. The present findings, indicating detrimental effects of life-long increased BDNF in mice, may inform human studies evaluating the role of BDNF functional genetic variations on cognitive abilities and vulnerability to psychiatric disorders. PMID:21791566

  9. 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.

  10. The Gut-Brain Axis, BDNF, NMDA and CNS Disorders.

    Science.gov (United States)

    Maqsood, Raeesah; Stone, Trevor W

    2016-11-01

    Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.

  11. Alterations in grooming activity and syntax in heterozygous SERT and BDNF knockout mice: the utility of behavior-recognition tools to characterize mutant mouse phenotypes.

    Science.gov (United States)

    Kyzar, Evan J; Pham, Mimi; Roth, Andrew; Cachat, Jonathan; Green, Jeremy; Gaikwad, Siddharth; Kalueff, Allan V

    2012-12-01

    Serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) are key modulators of molecular signaling, cognition and behavior. Although SERT and BDNF mutant mouse phenotypes have been extensively characterized, little is known about their self-grooming behavior. Grooming represents an important behavioral domain sensitive to environmental stimuli and is increasingly used as a model for repetitive behavioral syndromes, such as autism and attention deficit/hyperactivity disorder. The present study used heterozygous ((+/-)) SERT and BDNF male mutant mice on a C57BL/6J background and assessed their spontaneous self-grooming behavior applying both manual and automated techniques. Overall, SERT(+/-) mice displayed a general increase in grooming behavior, as indicated by more grooming bouts and more transitions between specific grooming stages. SERT(+/-) mice also aborted more grooming bouts, but showed generally unaltered activity levels in the observation chamber. In contrast, BDNF(+/-) mice displayed a global reduction in grooming activity, with fewer bouts and transitions between specific grooming stages, altered grooming syntax, as well as hypolocomotion and increased turning behavior. Finally, grooming data collected by manual and automated methods (HomeCageScan) significantly correlated in our experiments, confirming the utility of automated high-throughput quantification of grooming behaviors in various genetic mouse models with increased or decreased grooming phenotypes. Taken together, these findings indicate that mouse self-grooming behavior is a reliable behavioral biomarker of genetic deficits in SERT and BDNF pathways, and can be reliably measured using automated behavior-recognition technology. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. BDNF Variants May Modulate Long-Term Visual Memory Performance in a Healthy Cohort

    Directory of Open Access Journals (Sweden)

    Nesli Avgan

    2017-03-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265 and long-term visual memory (p-value = 0.003 in a small cohort (n = 181 comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale—Fourth Edition subtests Visual Reproduction I and II (VR I and II. VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism (p-value = 0.006 that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF, and its anti-sense transcript BDNF-AS, in long-term visual memory performance.

  13. On the quest for a biomechanism of transsexualism: is there a role for BDNF?

    Science.gov (United States)

    Fuss, Johannes; Biedermann, Sarah V; Stalla, Günter K; Auer, Matthias K

    2013-12-01

    Previous studies hypothesized a neurobiological mechanism for gender identity disorder (GID). Recently a possible role for serum brain-derived neurotrophic factor (BDNF) was suggested on the basis of reduced serum BDNF levels in male-to-female individuals. Here we review the question whether there is indeed a role of BDNF in the development of transsexualism. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. BDNF Variants May Modulate Long-Term Visual Memory Performance in a Healthy Cohort.

    Science.gov (United States)

    Avgan, Nesli; Sutherland, Heidi G; Spriggens, Lauren K; Yu, Chieh; Ibrahim, Omar; Bellis, Claire; Haupt, Larisa M; Shum, David H K; Griffiths, Lyn R

    2017-03-17

    Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265) and long-term visual memory ( p -value = 0.003) in a small cohort ( n = 181) comprised of healthy individuals who had been phenotyped for various aspects of memory function. In this study, we have extended the cohort to 597 individuals and examined multiple genetic variants across both the BDNF and BDNF-AS genes for association with visual memory performance as assessed by the Wechsler Memory Scale-Fourth Edition subtests Visual Reproduction I and II (VR I and II). VR I assesses immediate visual memory, whereas VR II assesses long-term visual memory. Genetic association analyses were performed for 34 single nucleotide polymorphisms genotyped on Illumina OmniExpress BeadChip arrays with the immediate and long-term visual memory phenotypes. While none of the BDNF and BDNF-AS variants were shown to be significant for immediate visual memory, we found 10 variants (including the Val66Met polymorphism ( p -value = 0.006)) that were nominally associated, and three variants (two variants in BDNF and one variant in the BDNF-AS locus) that were significantly associated with long-term visual memory. Our data therefore suggests a potential role for BDNF , and its anti-sense transcript BDNF-AS , in long-term visual memory performance.

  15. Expression and methylation of BDNF in the human brain in schizophrenia.

    Science.gov (United States)

    Cheah, Sern-Yih; McLeay, Robert; Wockner, Leesa F; Lawford, Bruce R; Young, Ross McD; Morris, Charles P; Voisey, Joanne

    2017-08-01

    To examine the combined effect of the BDNF Val66Met (rs6265) polymorphism and BDNF DNA methylation on transcriptional regulation of the BDNF gene. DNA methylation profiles were generated for CpG sites proximal to Val66Met, within BDNF promoter I and exon V for prefrontal cortex samples from 25 schizophrenia and 25 control subjects. Val66Met genotypes and BDNF mRNA expression data were generated by transcriptome sequencing. Expression, methylation and genotype data were correlated and examined for association with schizophrenia. There was 43% more of the BDNF V-VIII-IX transcript in schizophrenia samples. BDNF mRNA expression and DNA methylation of seven CpG sites were not associated with schizophrenia after accounting for age and PMI effects. BDNF mRNA expression and DNA methylation were not altered by Val66Met after accounting for age and PMI effects. DNA methylation of one CpG site had a marginally significant positive correlation with mRNA expression in schizophrenia subjects. Schizophrenia risk was not associated with differential BDNF mRNA expression and DNA methylation. A larger age-matched cohort with comprehensive clinical history is required to accurately identify the effects of genotype, mRNA expression and DNA methylation on schizophrenia risk.

  16. Increased blood BDNF in healthy individuals with a family history of depression

    DEFF Research Database (Denmark)

    Knorr, Ulla; Søndergaard, Mia H Greisen; Koefoed, Pernille

    2017-01-01

    The brain-derive neurotrophic factor (BDNF) may play an important role in the course of depression. We aimed to study the associations between peripheral whole blood BDNF levels in healthy individuals with and without a family history of depression. BDNF levels were significantly increased...... in healthy individuals with (n = 76), compared with healthy individuals without (n = 39) a family history of depression and persisted after adjustment for age and gender differences. Higher BDNF levels were associated with increasing age and seasonality. A family history of depression may contribute...

  17. Negative affectivity moderated by BDNF and stress response.

    Science.gov (United States)

    Perea, C S; Paternina, A C; Gomez, Y; Lattig, M C

    2012-02-01

    Gene×environment (G×E) interactions are known to predict susceptibility to disorders such as depression and anxiety. Adverse experiences in childhood and number of stressful life events (SLEs) have been widely studied as environmental risk factors; however, SLE response has not yet been studied. Here we present a first attempt at the analysis of the interaction between the response to personal and academic stressful events during different life stages and the gene polymorphisms 5-HTTLPR, 5-HTTVNTR (STin2), HTR1A C(-1019)G, and BDNF Val66Met in the prediction of negative affectivity (NA). Standardized questionnaires (ST-DEP and STAI) were used to measure negative affectivity derived from depression and anxiety in a sample of 303 undergraduate students. Response to stressful events during childhood, high school and college years was evaluated together with a self-report personal history form. Multiple logistic regression analysis was used to perform association and G×E analysis. Negative affectivity is strongly associated with childhood maltreatment and stress response. Gene associations were observed between 5-HTTVNTR allele 12 and the S_12 haplotype with NA derived from high scores in both depression and anxiety. The BDNF gene variant was not associated with NA derived from depression or anxiety alone, but it was associated with the comorbid presentation. A significant G×E interaction was observed between the BDNF Val66Met and stress response during childhood and college years although the risk for negative affectivity conferred by stress response during childhood was only significant among the Met allele carriers, while stress response during college years was a significant risk factor regardless of the BDNF Val66Met genotype. A significant G×E interaction was also found between the HTR1A C(-1019)G variant and childhood maltreatment. The study has two main limitations, sample size is low and retrospective recognition of SLEs is a concern. Altogether, our

  18. ProBDNF/p75NTR/sortilin pathway is activated in peripheral blood of patients with alcohol dependence.

    Science.gov (United States)

    Zhou, Li; Xiong, Jing; Ruan, Chun-Sheng; Ruan, Ye; Liu, Dennis; Bao, Jian-Jun; Zhou, Xin-Fu

    2018-03-09

    Alcohol dependence is a worldwide problem with a great social and economic burden in many countries. A number of studies have suggested that BDNF (mature BDNF) and its precursor (proBDNF) play important roles in the alcohol dependence. However, what roles of the mBDNF/proBDNF pathways play during the pathological process of alcohol dependence are not clearly understood. In our clinical study, peripheral blood was sampled from 30 male patients with alcohol dependence and 50 healthy males (as control). The protein levels of proBDNF, p75NTR, sortilin, mBDNF, TrkB and mRNA levels of BDNF, p75NTR, sortilin, and TrkB were detected in the peripheral blood in our study. We found that the protein levels of proBDNF and p75NTR were increased, but not the sortilin protein level; while the TrkB protein level was decreased in the alcohol dependence patients compared with healthy controls. Moreover, the mRNA levels of p75NTR and sortilin from the lymphocytes were slightly increased; while BDNF and TrkB were significantly decreased. The ELISA results of mBDNF and TrkB were declined in the alcohol dependence group. The levels of mBDNF and TrkB were negatively correlated with the average amount of daily ethanol consumption, and the levels of proBDNF, p75NTR and sortilin were positively correlated with the average amount of ethanol consumption per day. The ratio of proBDNF to mBDNF was altered in alcohol dependence patients. The balance between the proBDNF/p75NTR and mBDNF/TrkB signalling pathways appeared dysregulated in alcohol dependence. Our results suggested that both pathways may participate in the complex processes of alcohol dependence.

  19. The BDNF val-66-met Polymorphism Affects Neuronal Morphology and Synaptic Transmission in Cultured Hippocampal Neurons from Rett Syndrome Mice

    Directory of Open Access Journals (Sweden)

    Xin Xu

    2017-07-01

    Full Text Available Brain-derived neurotrophic factor (Bdnf has been implicated in several neurological disorders including Rett syndrome (RTT, an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2. The human BDNF gene has a single nucleotide polymorphism (SNP—a methionine (met substitution for valine (val at codon 66—that affects BDNF’s trafficking and activity-dependent release and results in cognitive dysfunction. Humans that are carriers of the met-BDNF allele have subclinical memory deficits and reduced hippocampal volume and activation. It is still unclear whether this BDNF SNP affects the clinical outcome of RTT individuals. To evaluate whether this BDNF SNP contributes to RTT pathophysiology, we examined the consequences of expression of either val-BDNF or met-BDNF on dendrite and dendritic spine morphology, and synaptic function in cultured hippocampal neurons from wildtype (WT and Mecp2 knockout (KO mice. Our findings revealed that met-BDNF does not increase dendritic growth and branching, dendritic spine density and individual spine volume, and the number of excitatory synapses in WT neurons, as val-BDNF does. Furthermore, met-BDNF reduces dendritic complexity, dendritic spine volume and quantal excitatory synaptic transmission in Mecp2 KO neurons. These results suggest that the val-BDNF variant contributes to RTT pathophysiology, and that BDNF-based therapies should take into consideration the BDNF genotype of the RTT individuals.

  20. 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

    The most well-described defect in the pathophysiology of type 2 diabetes is reduced insulin-mediated glycogen synthesis in skeletal muscles. It is unclear whether this defect is primary or acquired secondary to dyslipidemia, hyperinsulinemia, or hyperglycemia. We determined the glycogen synthase...

  1. 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.

  2. 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.

  3. Use of Brevibacillus choshinensis for the production of biologically active brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Angart, Phillip A; Carlson, Rebecca J; Thorwall, Sarah; Patrick Walton, S

    2017-07-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family critical for neuronal cell survival and differentiation, with therapeutic potential for the treatment of neurological disorders and spinal cord injuries. The production of recombinant, bioactive BDNF is not practical in most traditional microbial expression systems because of the inability of the host to correctly form the characteristic cystine-knot fold of BDNF. Here, we investigated Brevibacillus choshinensis as a suitable expression host for bioactive BDNF expression, evaluating the effects of medium type (2SY and TM), temperature (25 and 30 °C), and culture time (48-120 h). Maximal BDNF bioactivity (per unit mass) was observed in cultures grown in 2SY medium at extended times (96 h at 30 °C or >72 h at 25 °C), with resulting bioactivity comparable to that of a commercially available BDNF. For cultures grown in 2SY medium at 25 °C for 72 h, the condition that led to the greatest quantity of biologically active protein in the shortest culture time, we recovered 264 μg/L of BDNF. As with other microbial expression systems, BDNF aggregates did form in all culture conditions, indicating that while we were able to recover biologically active BDNF, further optimization of the expression system could yield still greater quantities of bioactive protein. This study provides confirmation that B. choshinensis is capable of producing biologically active BDNF and that further optimization of culture conditions could prove valuable in increasing BDNF yields.

  4. Transportation

    International Nuclear Information System (INIS)

    Anon.

    1998-01-01

    Here is the decree of the thirtieth of July 1998 relative to road transportation, to trade and brokerage of wastes. It requires to firms which carry out a road transportation as well as to traders and to brokers of wastes to declare their operations to the prefect. The declaration has to be renewed every five years. (O.M.)

  5. BDNF serum levels are not related to cognitive functioning in older depressed patients and controls

    NARCIS (Netherlands)

    Dols, A.; Thesing, C.; Bouckaert, F.; Oude Voshaar, R.C.; Comijs, H.C.; Stek, M.L.

    2015-01-01

    Background: Depression and cognitive decline are highly prevalent in older persons and both are associated with low serum brain derived neurotrophic factor (BDNF). Mutual pathways of depression and cognitive decline in older persons may explain the overlap in symptoms and low serum BDNF. We

  6. BDNF serum levels are not related to cognitive functioning in older depressed patients and controls

    NARCIS (Netherlands)

    Dols, A.; Thesing, C.S.; Bouckaert, F.; Oude Voshaar, R.C.; Comijs, H.C.; Stek, M.L.

    2015-01-01

    BACKGROUND: Depression and cognitive decline are highly prevalent in older persons and both are associated with low serum brain derived neurotrophic factor (BDNF). Mutual pathways of depression and cognitive decline in older persons may explain the overlap in symptoms and low serum BDNF. We

  7. Efficient use of a translation start codon in BDNF exon I.

    Science.gov (United States)

    Koppel, Indrek; Tuvikene, Jürgen; Lekk, Ingrid; Timmusk, Tõnis

    2015-09-01

    The brain-derived neurotrophic factor (BDNF) gene contains a number of 5' exons alternatively spliced with a common 3' exon. BDNF protein is synthesized from alternative transcripts as a prepro-precursor encoded by the common 3' exon IX, which has a translation start site 21 bp downstream of the splicing site. BDNF mRNAs containing exon I are an exception to this arrangement as the last three nucleotides of this exon constitute an in-frame AUG. Here, we show that this AUG is efficiently used for translation initiation in PC12 cells and cultured cortical neurons. Use of exon I-specific AUG produces higher levels of BDNF protein than use of the common translation start site, resulting from a higher translation rate. No differences in protein degradation, constitutive or regulated secretion were detected between BDNF isoforms with alternative 5' termini. As the BDNF promoter preceding exon I is known to be highly regulated by neuronal activity, our results suggest that the function of this translation start site may be efficient stimulus-dependent synthesis of BDNF protein. The brain-derived neurotrophic factor (BDNF) gene contains multiple untranslated 5' exons alternatively spliced to one common protein-coding 3' exon. However, exon I contains an in-frame ATG in a favorable translation context. Here, we show that use of this ATG is associated with more efficient protein synthesis than the commonly used ATG in exon IX. © 2015 International Society for Neurochemistry.

  8. BDNF val66met genotype and schizotypal personality traits interact to influence probabilistic association learning.

    Science.gov (United States)

    Skilleter, Ashley Jayne; Weickert, Cynthia Shannon; Moustafa, Ahmed Abdelhalim; Gendy, Rasha; Chan, Mico; Arifin, Nur; Mitchell, Philip Bowden; Weickert, Thomas Wesley

    2014-11-01

    The brain derived neurotrophic factor (BDNF) val66met polymorphism rs6265 influences learning and may represent a risk factor for schizophrenia. Healthy people with high schizotypal personality traits display cognitive deficits that are similar to but not as severe as those observed in schizophrenia and they can be studied without confounds of antipsychotics or chronic illness. How genetic variation in BDNF may impact learning in individuals falling along the schizophrenia spectrum is unknown. We predicted that schizotypal personality traits would influence learning and that schizotypal personality-based differences in learning would vary depending on the BDNF val66met genotype. Eighty-nine healthy adults completed the Schizotypal Personality Questionnaire (SPQ) and a probabilistic association learning test. Blood samples were genotyped for the BDNF val66met polymorphism. An ANOVA was performed with BDNF genotype (val homozygotes and met-carriers) and SPQ score (high/low) as grouping variables and probabilistic association learning as the dependent variable. Participants with low SPQ scores (fewer schizotypal personality traits) showed significantly better learning than those with high SPQ scores. BDNF met-carriers displaying few schizotypal personality traits performed best, whereas BDNF met-carriers displaying high schizotypal personality traits performed worst. Thus, the BDNF val66met polymorphism appears to influence probabilistic association learning differently depending on the extent of schizotypal personality traits displayed. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  9. Effects of combined BDNF and GDNF treatment on cultured dopaminergic midbrain neurons

    DEFF Research Database (Denmark)

    Sautter, J; Meyer, Morten; Spenger, C

    1998-01-01

    -derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), or a combination of both. Dopamine content of the culture medium, the number of tyrosine hydroxylase-immunoreactive neurons, and culture volumes were moderately increased in the BDNF- and GDNF-treated cultures but significantly...

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

    Directory of Open Access Journals (Sweden)

    Kellie L Janke

    2015-07-01

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

  11. BDNF serum levels are not related to cognitive functioning in older depressed patients and controls

    NARCIS (Netherlands)

    Dols, Annemiek; Thesing, Carisha S.; Bouckaert, Filip; Oude Voshaar, Richard; Comijs, Hannie C.; Stek, M. L.

    Background: Depression and cognitive decline are highly prevalent in older persons and both are associated with low serum brain derived neurotrophic factor (BDNF). Mutual pathways of depression and cognitive decline in older persons may explain the overlap in symptoms and low serum BDNF. We

  12. 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.

  13. 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.

  14. Obesity itself does not influence BDNF serum levels in adults.

    Science.gov (United States)

    Gajewska, E; Sobieska, M; Łojko, D; Wieczorowska-Tobis, K; Suwalska, A

    2014-01-01

    In European countries more than 50% of the population are overweight, 30% with obesity. In Poland overweight was present in 41% of men and 28.7% of women (obesity 15.7% and 19.9%). It was examined whether obesity affects serum levels of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6), which may lead to the consequences of obesity, such as type 2 diabetes, hypertension, and finally the metabolic syndrome. We aimed to examine whether obesity affects the serum levels of BDNF and IL-6. The study involved 144 people aged 45 to 86 years, 80 subjects with diagnosed obesity and 64 with normal body weight, ≤ 65 years old (n = 45) and > 65 years old (n = 99). All patients underwent tests of glucose, total cholesterol, HDL, LDL, triglycerides levels, using routine laboratory methods. A test of the concentration of IL-6 and BDNF was carried out. The declared level of physical activity (gymnastics, cycling or walking) was considered. It was shown that in women ≤ 65 years old, obesity was associated with higher levels of interleukin-6. When the test group, divided into the above categories, was analyzed for the diagnosis of hypertension, heart failure or diabetes mellitus, no statistically significant differences in the investigated parameters were detected. The concentration of brain-derived neurotrophic factor did not differ in the investigated subjects, regardless of sex, age, obesity, or the declared physical activity. The concentration of interleukin-6 in younger people, including those with normal body weight, correlated with total cholesterol and triglyceride levels, and it was significantly higher in obese women compared to those with normal body weight.

  15. Transportation

    National Research Council Canada - National Science Library

    Allshouse, Michael; Armstrong, Frederick Henry; Burns, Stephen; Courts, Michael; Denn, Douglas; Fortunato, Paul; Gettings, Daniel; Hansen, David; Hoffman, Douglas; Jones, Robert

    2007-01-01

    .... The ability of the global transportation industry to rapidly move passengers and products from one corner of the globe to another continues to amaze even those wise to the dynamics of such operations...

  16. Defects and defect processes in nonmetallic solids

    CERN Document Server

    Hayes, W

    2004-01-01

    This extensive survey covers defects in nonmetals, emphasizing point defects and point-defect processes. It encompasses electronic, vibrational, and optical properties of defective solids, plus dislocations and grain boundaries. 1985 edition.

  17. Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation.

    Science.gov (United States)

    Zhang, Xin; Zeng, Lulu; Yu, Tingting; Xu, Yongming; Pu, Shaofeng; Du, Dongping; Jiang, Wei

    2014-01-01

    Microglia, which represent the immune cells of the central nervous system (CNS), have long been a subject of study in CNS disease research. Substantial evidence indicates that microglial activation functions as a strong neuro-inflammatory response in neuropathic pain, promoting the release of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α. In addition, activated microglia release brain-derived neurotrophic factor (BDNF), which acts as a powerful cytokine. In this study, we performed a series of in vitro experiments to examine whether a positive autocrine feedback loop existed between microglia-derived BDNF and subsequent microglial activation as well as the mechanisms underlying this positive feedback loop. Because ATP is a classic inducer of microglial activation, firstly, we examined ATP-activated microglia in the present study. Secondly, we used TrkB/Fc, the BDNF sequester, to eliminate the effects of endogenous BDNF. ATP-stimulated microglia without BDNF was examined. Finally, we used exogenous BDNF to further determine whether BDNF could directly activate BV2 microglia. In all experiments, to quantify BV2 microglia activation, the protein levels of CD11b, a microglial activation marker, were measured by western blot. A Transwell migration assay was used to examine microglial migration. To assess the synthesis and release of proinflammatory cytokines, western blot was used to measure BDNF synthesis, and ELISA was used to quantify TNF-α release. In our present research, we have observed that ATP dramatically activates microglia, enhancing microglial migration, increasing the synthesis of BDNF and up-regulating the release of TNF-α. Microglial activation is inhibited following the sequestration of endogenous BDNF, resulting in impaired microglial migration and decreased TNF-α release. Furthermore, exogenous BDNF can also activate microglia to subsequently enhance migration and increase TNF-α release. Therefore, we suggest that microglial

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

    International Nuclear Information System (INIS)

    Halepoto, D. M.; Bashir, S.; AL-Ayadhi, L.

    2014-01-01

    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)

  19. No association between polymorphisms in the BDNF gene and age at onset in Huntington disease

    Directory of Open Access Journals (Sweden)

    Kraus Peter H

    2006-11-01

    Full Text Available Abstract Background Recent evidence suggests that brain-derived neurotrophic factor (BDNF is an attractive candidate for modifying age at onset (AO in Huntington disease (HD. In particular, the functional Val66Met polymorphism appeared to exert a significant effect. Here we evaluate BDNF variability with respect to AO of HD using markers that represent the entire locus. Methods Five selected tagging polymorphisms were genotyped across a 65 kb region comprising the BDNF gene in a well established cohort of 250 unrelated German HD patients. Results Addition of BDNF genotype variations or one of the marker haplotypes to the effect of CAG repeat lengths did not affect the variance of the AO. Conclusion We were unable to verify a recently reported association between the functional Val66Met polymorphism in the BDNF gene and AO in HD. From our findings, we conclude that neither sequence variations in nor near the gene contribute significantly to the variance of AO.

  20. Reduced serum concentrations of brain-derived neurotrophic factor (BDNF) in transsexual Brazilian men.

    Science.gov (United States)

    Fontanari, Anna Martha Vaitses; Costa, Angelo Brandelli; Aguiar, Bianca; Tusset, Cíntia; Andreazza, Tahiana; Schneider, Maiko; da Rosa, Eduarda Dias; Soll, Bianca Machado Borba; Schwarz, Karine; da Silva, Dhiordan Cardoso; Borba, André Oliveira; Mueller, Andressa; Massuda, Raffael; Lobato, Maria Inês Rodrigues

    2016-09-06

    Serum BDNF levels are significantly decreased in transsexual Brazilian women when compared to cis-sexual men. Since transsexual men are also exposed to chronic social stress and have a high prevalence of associated psychopathologies, it is plausible to inquire if BDNF serum levels are altered in transsexual men as well. Therefore, our objective was to evaluate differences in BDNF serum level of transsexual men when compared to cis-sexual men and women. Our sample comprises 27 transsexual men, 31 cis-sexual women and 30 cis-sexual men recruited between 2011 and 2015. We observed that BDNF serum concentration is decreased in transsexual men comparing to cis-sexual men and women. Cross-sex hormone treatment, chronic social stress or long-term gender dysphoria (GD) could explain the variation found in BDNF serum levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.

    Science.gov (United States)

    Chen, Mei-Rong; Dai, Ping; Wang, Shu-Fen; Song, Shu-Hua; Wang, Hang-Ping; Zhao, Ya; Wang, Ting-Hua; Liu, Jia

    2016-10-01

    Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

  2. Early raise of BDNF in hippocampus suggests induction of posttranscriptional mechanisms by antidepressants

    Directory of Open Access Journals (Sweden)

    Barlati Sergio

    2009-05-01

    Full Text Available Abstract Background The neurotrophin BDNF has been implicated in the regulation of neuroplasticity, gene expression, and synaptic function in the adult brain, as well as in the pathophysiology of neuropsychiatric disorders and the mechanism of action of antidepressants. Antidepressant treatments have been shown to increase the expression of BDNF mRNA, although the changes measured were found to be different depending on various factors. A few studies only have measured levels of BDNF protein after antidepressant treatments, and poor correlation was found between mRNA and protein changes. We studied the time course of expression of BDNF mRNA and protein during drug treatments, in order to elucidate the temporal profile of regulation of this effector and whether mRNA and protein levels correlate. Rat groups were treated for 1, 2 or 3 weeks with fluoxetine or reboxetine; in additional groups drug treatment was followed by a washout week (3+1. Total BDNF mRNA was measured by Real Time PCR, pro- and mature BDNF proteins were measured by Western blot. Results We found that mature BDNF protein is induced more rapidly than mRNA, by both drugs in hippocampus (weeks 1–2 and by reboxetine in prefrontal/frontal cortex (week 1. The temporal profile of BDNF protein expression was largely inconsistent with that of mRNA, which followed the protein induction and reached a peak at week 3. Conclusion These results suggest that BDNF protein is rapidly elevated by antidepressant treatments by posttranscriptional mechanisms, and that induction of BDNF mRNA is a slower process.

  3. Complete spinal cord injury (SCI) transforms how brain derived neurotrophic factor (BDNF) affects nociceptive sensitization.

    Science.gov (United States)

    Huang, Yung-Jen; Lee, Kuan H; Grau, James W

    2017-02-01

    Noxious stimulation can induce a lasting increase in neural excitability within the spinal cord (central sensitization) that can promote pain and disrupt adaptive function (maladaptive plasticity). Brain-derived neurotrophic factor (BDNF) is known to regulate the development of plasticity and has been shown to impact the development of spinally-mediated central sensitization. The latter effect has been linked to an alteration in GABA-dependent inhibition. Prior studies have shown that, in spinally transected rats, exposure to regular (fixed spaced) stimulation can counter the development of maladaptive plasticity and have linked this effect to an up-regulation of BDNF. Here it is shown that application of the irritant capsaicin to one hind paw induces enhanced mechanical reactivity (EMR) after spinal cord injury (SCI) and that the induction of this effect is blocked by pretreatment with fixed spaced shock. This protective effect was eliminated if rats were pretreated with the BDNF sequestering antibody TrkB-IgG. Intrathecal (i.t.) application of BDNF prevented, but did not reverse, capsaicin-induced EMR. BDNF also attenuated cellular indices (ERK and pERK expression) of central sensitization after SCI. In uninjured rats, i.t. BDNF enhanced, rather than attenuated, capsaicin-induced EMR and ERK/pERK expression. These opposing effects were related to a transformation in GABA function. In uninjured rats, BDNF reduced membrane-bound KCC2 and the inhibitory effect of the GABA A agonist muscimol. After SCI, BDNF increased KCC2 expression, which would help restore GABAergic inhibition. The results suggest that SCI transforms how BDNF affects GABA function and imply that the clinical usefulness of BDNF will depend upon the extent of fiber sparing. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. AP-1 Transcription Factors Mediate BDNF-Positive Feedback Loop in Cortical Neurons.

    Science.gov (United States)

    Tuvikene, Jürgen; Pruunsild, Priit; Orav, Ester; Esvald, Eli-Eelika; Timmusk, Tõnis

    2016-01-27

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, regulates both survival and differentiation of several neuronal populations in the nervous system during development, as well as synaptic plasticity in the adult brain. BDNF exerts its biological functions through its receptor TrkB. Although the regulation of BDNF transcription by neuronal activity has been widely studied, little is known about TrkB signaling-dependent expression of BDNF. Using rat primary cortical neuron cultures, we show that the BDNF gene is a subject to an extensive autoregulatory loop, where TrkB signaling upregulates the expression of all major BDNF transcripts, mainly through activating MAPK pathways. Investigating the mechanisms behind this autoregulation, we found that AP-1 transcription factors, comprising Jun and Fos family members, participate in the induction of BDNF exon I, III, and VI transcripts. AP-1 transcription factors directly upregulate the expression of exon I transcripts by binding two novel AP-1 cis-elements in promoter I. Moreover, our results show that the effect of AP-1 proteins on the activity of rat BDNF promoters III and VI is indirect, because AP-1 proteins were not detected to bind the respective promoter regions by chromatin immunoprecipitation (ChIP). Collectively, we describe an extensive positive feedback system in BDNF regulation, adding a new layer to the elaborate control of BDNF gene expression. Here, we show for the first time that in rat primary cortical neurons the expression of all major BDNF transcripts (exon I, II, III, IV, VI, and IXa transcripts) is upregulated in response to TrkB signaling, and that AP-1 transcription factors participate in the induction of exon I, III, and VI transcripts. Moreover, we have described two novel functional AP-1 cis-elements in BDNF promoter I, responsible for the activation of the promoter in response to TrkB signaling. Our results indicate the existence of a positive feedback loop for

  5. BDNF promotes target innervation of Xenopus mandibular trigeminal axons in vivo.

    Science.gov (United States)

    Huang, Jeffrey K; Dorey, Karel; Ishibashi, Shoko; Amaya, Enrique

    2007-05-31

    Trigeminal nerves consist of ophthalmic, maxillary, and mandibular branches that project to distinct regions of the facial epidermis. In Xenopus embryos, the mandibular branch of the trigeminal nerve extends toward and innervates the cement gland in the anterior facial epithelium. The cement gland has previously been proposed to provide a short-range chemoattractive signal to promote target innervation by mandibular trigeminal axons. Brain derived neurotrophic factor, BDNF is known to stimulate axon outgrowth and branching. The goal of this study is to determine whether BDNF functions as the proposed target recognition signal in the Xenopus cement gland. We found that the cement gland is enriched in BDNF mRNA transcripts compared to the other neurotrophins NT3 and NT4 during mandibular trigeminal nerve innervation. BDNF knockdown in Xenopus embryos or specifically in cement glands resulted in the failure of mandibular trigeminal axons to arborise or grow into the cement gland. BDNF expressed ectodermal grafts, when positioned in place of the cement gland, promoted local trigeminal axon arborisation in vivo. BDNF is necessary locally to promote end stage target innervation of trigeminal axons in vivo, suggesting that BDNF functions as a short-range signal that stimulates mandibular trigeminal axon arborisation and growth into the cement gland.

  6. Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice.

    Directory of Open Access Journals (Sweden)

    Kim M Gerecke

    Full Text Available Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF, have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is dependent upon BDNF, we compared the neuroprotective effects of voluntary exercise in mice heterozygous for the BDNF gene (BDNF+/- with strain-matched wild-type (WT mice. Stereological estimates of SNpc DA neurons from WT mice allowed 90 days exercise via unrestricted running demonstrated complete protection against the MPTP-induced neurotoxicity. However, BDNF+/- mice allowed 90 days of unrestricted exercise were not protected from MPTP-induced SNpc DA neuron loss. Proteomic analysis comparing SN and striatum from 90 day exercised WT and BDNF+/- mice showed differential expression of proteins related to energy regulation, intracellular signaling and trafficking. These results suggest that a full genetic complement of BDNF is critical for the exercise-induced neuroprotection of SNpc DA neurons.

  7. Brain-derived Neurotrophic Factor (BDNF) and gray matter volume in bipolar disorder.

    Science.gov (United States)

    Poletti, S; Aggio, V; Hoogenboezem, T A; Ambrée, O; de Wit, H; Wijkhuijs, A J M; Locatelli, C; Colombo, C; Arolt, V; Drexhage, H A; Benedetti, F

    2017-02-01

    Bipolar Disorder (BD) is a severe psychiatric condition characterized by grey matter (GM) volumes reduction. Neurotrophic factors have been suggested to play a role in the neuroprogressive changes during the illness course. In particular peripheral brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in BD. The aim of our study was to investigate if serum levels of BDNF are associated with GM volumes in BD patients and healthy controls (HC). We studied 36 inpatients affected by a major depressive episode in course of BD type I and 17 HC. Analysis of variance was performed to investigate the effect of diagnosis on GM volumes in the whole brain. Threshold for significance was Pbrain areas, encompassing the caudate head, superior temporal gyrus, insula, fusiform gyrus, parahippocampal gyrus, and anterior cingulate cortex. The interaction analysis between BDNF levels and diagnosis showed a significant effect in the middle frontal gyrus. HC reported higher BDNF levels associated with higher GM volumes, whereas no association between BDNF and GM volumes was observed in BD. Our study seems to suggest that although the production of BDNF is increased in BD possibly to prevent and repair neural damage, its effects could be hampered by underlying neuroinflammatory processes interfering with the neurodevelopmental role of BDNF. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

    Science.gov (United States)

    Lim, Won-Chul; Kim, Hyunhee; Kim, Young-Joo; Park, Seung-Ho; Song, Ji-Hye; Lee, Ki Heon; Lee, In Ho; Lee, Yoo-Kyung; So, Kyeong A; Choi, Kyung-Chul; Ko, Hyeonseok

    2017-12-01

    Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. The requirement of BDNF for hippocampal synaptic plasticity is experience-dependent.

    Science.gov (United States)

    Aarse, Janna; Herlitze, Stefan; Manahan-Vaughan, Denise

    2016-06-01

    Brain-derived neurotrophic factor (BDNF) supports neuronal survival, growth, and differentiation and has been implicated in forms of hippocampus-dependent learning. In vitro, a specific role in hippocampal synaptic plasticity has been described, although not all experience-dependent forms of synaptic plasticity critically depend on BDNF. Synaptic plasticity is likely to enable long-term synaptic information storage and memory, and the induction of persistent (>24 h) forms, such as long-term potentiation (LTP) and long-term depression (LTD) is tightly associated with learning specific aspects of a spatial representation. Whether BDNF is required for persistent (>24 h) forms of LTP and LTD, and how it contributes to synaptic plasticity in the freely behaving rodent has never been explored. We examined LTP, LTD, and related forms of learning in the CA1 region of freely dependent mice that have a partial knockdown of BDNF (BDNF(+/-) ). We show that whereas early-LTD (synaptic plasticity may circumvent the need for BDNF, rather it may play a specific role in the optimization of weaker forms of plasticity. The finding that both learning-facilitated LTD and spatial reference memory are both impaired in BDNF(+/-) mice, suggests moreover, that it is critically required for the physiological encoding of hippocampus-dependent memory. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  10. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

    Directory of Open Access Journals (Sweden)

    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  11. 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

  12. Effects of crack cocaine addiction and stress-related genes on peripheral BDNF levels.

    Science.gov (United States)

    Rovaris, Diego L; Schuch, Jaqueline B; Grassi-Oliveira, Rodrigo; Sanvicente-Vieira, Breno; da Silva, Bruna S; Walss-Bass, Consuelo; Müller, Diana; Stolf, Anderson R; von Diemen, Lisia; Ceresér, Keila M M; Pianca, Thiago G; Szobot, Claudia M; Kessler, Felix H P; Roman, Tatiana; Bau, Claiton H D

    2017-07-01

    This study examined the effects of glucocorticoid receptor (NR3C1), corticotropin-releasing hormone receptor 1 (CRHR1), and brain-derived neurotrophic factor (BDNF) genes on susceptibility to crack cocaine addiction and BDNF levels. Crack addicted patients who sought treatment (n = 280) and non-addicted individuals (n = 241) were assessed. Three SNPs in NR3C1 (rs6198, rs41423247, and rs10052957), three in CRHR1 (rs12944712, rs110402, and rs878886), and one in BDNF (rs6265) were genotyped. No significant effect was seen in the case-control analyses. Crack cocaine addicted patients showed significantly lower serum BDNF levels. Significant effects were observed for NR3C1 rs41423247 and rs10052957. These effects were restricted to non-addicted individuals and they were supported by significant gene-by-disease status interactions. For CRHR1, all SNPs were associated with BDNF levels. Although there were significant effects only in the analysis restricted to non-addicted individuals, the lack of significant results in the gene-by-disease status interaction analyses suggest a general effect on BDNF levels. The haplotype analyses presented the same effect seen in the single marker analyses. This study suggests that SNPs in the NR3C1 and CRHR1 genes may influence BDNF levels, but this effect is blunted in the context of crack cocaine addiction. Therefore, our data may be interpreted in light of several studies showing pronounced effects of crack cocaine on BDNF levels. Since peripheral BDNF is a biomarker for several psychiatric phenotypes, our results may be useful in interpreting previous associations between stress-related SNPs, drug addiction, and depression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. More Insight into BDNF against Neurodegeneration: Anti-Apoptosis, Anti-Oxidation, and Suppression of Autophagy

    Directory of Open Access Journals (Sweden)

    Shang-Der Chen

    2017-03-01

    Full Text Available In addition to its well-established neurotrophic action, brain-derived neurotrophic factor (BDNF also possesses other neuroprotective effects including anti-apoptosis, anti-oxidation, and suppression of autophagy. We have shown before that BDNF triggers multiple mechanisms to confer neuronal resistance against 3-nitropropionic acid (3-NP-induced mitochondrial dysfunction in primary rat cortical cultures. The beneficial effects of BDNF involve the induction of anti-oxidative thioredoxin with the resultant expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2 as well as erythropoietin (EPO-dependent stimulation of sonic hedgehog (SHH. We further revealed that BDNF may bring the expression of sulfiredoxin, an ATP-dependent antioxidant enzyme, to offset mitochondrial inhibition in cortical neurons. Recently, we provided insights into another novel anti-oxidative mechanism of BDNF, which involves the augmentation of sestrin2 expression to endow neuronal resistance against oxidative stress induced by 3-NP; BDNF induction of sestrin2 entails the activation of a pathway involving nitric oxide (NO, cyclic guanosine monophosphate (cGMP-dependent protein kinase (PKG, and nuclear factor-κB (NF-κB. Apart from anti-apoptosis and anti-oxidation, we demonstrated in our most recent study that BDNF may activate the mammalian target of rapamycin (mTOR with resultant activation of transcription factor c-Jun, thereby stimulating the expression of p62/sequestosome-1 to suppress heightened autophagy as a result of 3-NP exposure. Together, our results provide in-depth insight into multi-faceted protective mechanisms of BDNF against mitochondrial dysfunction commonly associated with the pathogenesis of many chronic neurodegenerative disorders. Delineation of the protective signaling pathways elicited by BDNF would endow a rationale to develop novel therapeutic regimens to halt or prevent the progression of neurodegeneration.

  14. Prenatal exposure to polycyclic aromatic hydrocarbons/aromatics, BDNF and child development.

    Science.gov (United States)

    Perera, Frederica; Phillips, David H; Wang, Ya; Roen, Emily; Herbstman, Julie; Rauh, Virginia; Wang, Shuang; Tang, Deliang

    2015-10-01

    Within a New York City (NYC) birth cohort, we assessed the associations between polycyclic aromatic hydrocarbon (PAH) and other aromatic DNA adducts and brain derived neurotrophic factor (BDNF) concentrations in umbilical cord blood, and neurodevelopment at age 2 years and whether BDNF is a mediator of the associations between PAH/aromatic-DNA adducts and neurodevelopment. PAH/aromatic-DNA adduct concentrations in cord blood were measured in 505 children born to nonsmoking African-American and Dominican women residing in NYC, and a subset was assessed for neurodevelopment at 2 years using the Bayley Scales of Infant Development Mental Development Index (MDI). A spectrum of PAH/aromatic-DNA adducts was measured using the (32)P-postlabeling assay; DNA adducts formed by benzo[a]pyrene (B[a]P), a representative PAH, were measured by High Performance Liquid Chromatography (HPLC)/fluorescence. BDNF mature protein in cord blood plasma was quantified by an ELISA. Multivariate regression analysis, adjusting for potential confounders, was conducted. PAH/aromatic-DNA adduct concentration measured by postlabeling was inversely associated with BDNF concentration (p=0.02) and with MDI scores at 2 years (p=0.04). BDNF level was positively associated with MDI scores (p=0.003). Restricting to subjects having all three measures (PAH/aromatic-DNA adducts by postlabeling, MDI, and BDNF), results were similar but attenuated (p=0.13, p=0.05, p=0.01, respectively). Associations between B[a]P-DNA adducts and BDNF and B[a]P-DNA adducts and MDI at age 2 years were not significant. At age 3 years, the positive association of BDNF with MDI was not observed. The results at age 2 suggest that prenatal exposure to a spectrum of PAH/aromatic pollutants may adversely affect early neurodevelopment, in part by reducing BDNF levels during the fetal period. However, the same relationship was not seen at age 3. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Association of BDNF Val66MET Polymorphism With Parkinson's Disease and Depression and Anxiety Symptoms.

    Science.gov (United States)

    Cagni, Fernanda Carvalho; Campêlo, Clarissa Loureiro das Chagas; Coimbra, Daniel Gomes; Barbosa, Mayara Rodrigues; Júnior, Luiz Gonzaga Oliveira; Neto, Antônio Braz Silva; Ribeiro, Alessandra Mussi; Júnior, Clécio de Oliveira Godeiro; Gomes de Andrade, Tiago; Silva, Regina Helena

    2017-01-01

    An association between Parkinson's disease (PD) and brain-derived neurotrophic factor (BDNF) was suggested by several studies, with contradictory results. BDNF is necessary for the survival of dopaminergic neurons in substantia nigra. Val66Met is a common polymorphism of the BDNF gene that affects cognitive and motor processes. The authors studied 104 Brazilian patients with PD and 96 control participants. The G/G genotype was significantly associated with depression and anxiety symptoms and development of PD. This is the first study that associates this genotype with PD.

  16. Postresuscitative Changes of Brain-Derived Neurotrophic Factor (BDNF Protein Expression: Association With Neuronal Death

    Directory of Open Access Journals (Sweden)

    M. Sh. Avrushchenko

    2017-01-01

    Full Text Available Aim of the study: to evaluate expression level of BDNF and its association with the postresuscitative neuronal death in highly hypoxia-sensitive brain regions.Materials and methods. Cardiac arrest in adult albino male rats was evoked by intrathoracic clamping of supracardiac bundle of vessels for 10 min. Pyramidal neurons of the hippocampus and Purkinje cells of the cerebellum were analyzed at various time points after resuscitation (days 1, 4, 7, 14. Shame-operated rats served as controls. The expression of BDNF protein was immunohistochemically determined. The BDNF expression level was determined by evalution on the base of the average optical density. The number of neurons with different BDNF expression levels and the total number of neurons per 1 mm of the layer length were computed. Image analysis systems (Intel personal computer, Olympus BX-41 microscope, ImageScopeM, ImageJ 1,48v and MS Excel 2007 software packages were used in the study. Data statistical processing was performed with the aid of Statistica 7.0 program and Kolmogorov-Smirnov λ-test, Mann-Whitney U-test and Student's t-test.Results. The dynamics of postresuscitative shifts of BDNF immunoreactivity in neuronal populations of hippocampal pyramidal cells and cerebellar Purkinje cells was established. It was shown that the level of BDNF expression within the two neuronal populations decreased, that was accompanied by neuronal death. In the Purkinje cell population the neuronal death occurred by the 4th day after resuscitation, while in the hippocampus, it occurs only by the 7th day. Notably, only BDNF-negative neurons or neurons with low level of BDNF expression died in both neuronal populations.Conclusion. The results of the study indicate the existence of an interrelation between the shifts in BDNF expression and the postresuscitative neuronal death. It was shown that only the cells with none or poor BDNF expression underwent death in highly hypoxia-sensitive neuronal

  17. Polymorphisms of the BDNF gene show neither association with multiple sclerosis susceptibility nor clinical course.

    Science.gov (United States)

    Mero, Inger-Lise; Smestad, Cathrine; Lie, Benedicte A; Lorentzen, Åslaug R; Sandvik, Leiv; Landrø, Nils Inge; Aarseth, Jan H; Myhr, Kjell-Morten; Celius, Elisabeth G; Harbo, Hanne F

    2012-03-01

    Brain-derived neurotrophic factor (BDNF) has been proposed a protective role in multiple sclerosis (MS) in several studies. The val(66)met polymorphism alters the function of the BDNF protein, and has along with rs56164415 previously been reported to be associated with MS. We genotyped BDNF SNPs val(66)met and rs56164415 in 2149 Norwegian MS patients and 2747 healthy controls. No association was found for any of the SNPs to disease susceptibility or any clinical or demographic parameters including sex, age at onset, disease course, disease severity and cognitive impairment. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Embedded defects

    International Nuclear Information System (INIS)

    Barriola, M.; Vachaspati, T.; Bucher, M.

    1994-01-01

    We give a prescription for embedding classical solutions and, in particular, topological defects in field theories which are invariant under symmetry groups that are not necessarily simple. After providing examples of embedded defects in field theories based on simple groups, we consider the electroweak model and show that it contains the Z string and a one-parameter family of strings called the W(α) string. It is argued that although the members of this family are gauge equivalent when considered in isolation, each member becomes physically distinct when multistring configurations are considered. We then turn to the issue of stability of embedded defects and demonstrate the instability of a large class of such solutions in the absence of bound states or condensates. The Z string is shown to be unstable for all values of the Higgs boson mass when θ W =π/4. W strings are also shown to be unstable for a large range of parameters. Embedded monopoles suffer from the Brandt-Neri-Coleman instability. Finally, we connect the electroweak string solutions to the sphaleron

  19. 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...

  20. School Bus Safety Issues. Hearing on Examining Defective Handrails Which Have Been Found on School Buses across the Country, the Need for a School Bus Specific Commercial Drivers' License, and the Use of Public Transportation by Students, of the Committee on Labor and Human Resources, United States Senate. One Hundred Fourth Congress, Second Session.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.

    The hearing was held to examine the following student-transportation safety issues: defective handrails on school buses; the need for a school-bus specific-commercial driver's license; and the use of public transportation by students. Senator Mike DeWine presided over the hearing. The document contains testimonies and prepared statements of…

  1. 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

    2009-01-01

    , the findings on the defect chemistry were reported, while the oxygen transport properties are reported here in part II. In the investigated material series, the amount of divalent dopant has been kept constant, while Sr ions have been substituted with Ca ions (smaller ionic radius) or Ba ions (larger ionic...... radius). The size difference induces different strains into the crystal structure in each composition. The possibility of simple relationships between various crystal strain parameters and the transport properties were analyzed. Oxygen pump controlled permeation experiments and a surface sensitive...

  2. 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.

  3. 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.

  4. BDNF and its receptors in human myasthenic thymus: implications for cell fate in thymic pathology.

    Science.gov (United States)

    Berzi, Angela; Ayata, C Korcan; Cavalcante, Paola; Falcone, Chiara; Candiago, Elisabetta; Motta, Teresio; Bernasconi, Pia; Hohlfeld, Reinhard; Mantegazza, Renato; Meinl, Edgar; Farina, Cinthia

    2008-07-15

    Here we show that in myasthenic thymus several cell types, including thymic epithelial cells (TEC) and immune cells, were the source and the target of the neurotrophic factor brain-derived growth factor (BDNF). Interestingly, many actively proliferating medullary thymocytes expressed the receptor TrkB in vivo in involuted thymus, while this population was lost in hyperplastic or neoplastic thymuses. Furthermore, in hyperplastic thymuses the robust coordinated expression of BDNF in the germinal centers together with the receptor p75NTR on all proliferating B cells strongly suggests that this factor regulates germinal center reaction. Finally, all TEC dying of apoptosis expressed BDNF receptors, indicating that this neurotrophin is involved in TEC turnover. In thymomas both BDNF production and receptor expression in TEC were strongly hindered. This may represent an attempt of tumour escape from cell death.

  5. 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...

  6. The Neuroprotective Role of Acupuncture and Activation of the BDNF Signaling Pathway

    Science.gov (United States)

    Lin, Dong; De La Pena, Ike; Lin, Lili; Zhou, Shu-Feng; Borlongan, Cesar V.; Cao, Chuanhai

    2014-01-01

    Recent studies have been conducted to examine the neuroprotective effects of acupuncture in many neurological disorders. Although the neuroprotective effects of acupuncture has been linked to changes in signaling pathways, accumulating evidence suggest the participation of endogenous biological mediators, such as the neurotrophin (NT) family of proteins, specifically, the brain derived neurotrophic factor (BDNF). Accordingly, acupuncture can inhibit neurodegeneration via expression and activation of BDNF. Moreover, recent studies have reported that acupuncture can increase ATP levels at local stimulated points. We have also demonstrated that acupuncture could activate monocytes and increase the expression of BDNF via the stimulation of ATP. The purpose of this article is to review the recent findings and ongoing studies on the neuroprotective roles of acupuncture and therapeutic implications of acupuncture-induced activation of BDNF and its signaling pathway. PMID:24566146

  7. 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

  8. Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

    OpenAIRE

    Jornada, Luciano K.; Valvassori, Samira S.; Resende, Wilson R.; Moretti, Morgana; Ferreira, Camila L.; Fries, Gabriel R.; Kapczinski, Flavio; Quevedo, João

    2012-01-01

    OBJECTIVE: The present study aims to investigate the effects of ouabain intracerebroventricular injection on BDNF levels in the amygdala and hippocampus of Wistar rats. METHODS: Animals received a single intracerebroventricular injection of ouabain (10-3 and 10-2 M) or artificial cerebrospinal fluid and immediately, 1h, 24h, or seven days after injection, BDNF levels were measured in the rat's amygdala and hippocampus by sandwich-ELISA (n = 8 animals per group). RESULTS: When evaluated immedi...

  9. Hypothalamic Gene Transfer of BDNF Inhibits Breast Cancer Progression and Metastasis in Middle Age Obese Mice

    OpenAIRE

    Liu, Xianglan; McMurphy, Travis; Xiao, Run; Slater, Andrew; Huang, Wei; Cao, Lei

    2014-01-01

    Activation of the hypothalamus-adipocyte axis is associated with an antiobesity and anticancer phenotype in animal models of melanoma and colon cancer. Brain-derived neurotrophic factor (BDNF) is a key mediator in the hypothalamus leading to preferential sympathoneural activation of adipose tissue and the ensuing resistance to obesity and cancer. Here, we generated middle age obese mice by high fat diet feeding for a year and investigated the effects of hypothalamic gene transfer of BDNF on a...

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

    Science.gov (United States)

    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 polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age x BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (p memory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory – in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). PMID:25264352

  11. Suicide attempt, clinical correlates, and BDNF Val66Met polymorphism in chronic patients with schizophrenia.

    Science.gov (United States)

    Xia, Haisen; Zhang, Guangya; Du, Xiangdong; Zhang, Yingyang; Yin, Guangzhong; Dai, Jing; He, Man-Xi; Soares, Jair C; Li, Xiaosi; Zhang, Xiang Yang

    2018-02-01

    Recent evidence suggests the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior. Because schizophrenia patients usually have high suicide rates and numerous studies have suggested that BDNF may contribute to the psychopathology of schizophrenia, we hypothesized that the functional polymorphism of BDNF (Val66Met) was associated with suicide attempts in patients with schizophrenia in a Chinese Han population. This polymorphism was genotyped in 825 chronic schizophrenia patients with (n = 123) and without (n = 702) suicide attempts and 445 healthy controls without a history of suicide attempts using a case-control design. The schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale. There were no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls. However, we found the Val allele (p = .023) and the Val/Val genotypes (p = .058) to be associated with a history of suicide attempts. Moreover, some clinical characteristics, including age and cigarettes smoked each day, interacted with the BDNF gene variant and appeared to play an important role in suicide attempts among schizophrenia patients. The BDNF Val66Met polymorphism itself and its interaction with some clinical variables may influence suicide attempts among schizophrenia patients. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  12. Effect of Clotting Duration and Temperature on BDNF Measurement in Human Serum

    Science.gov (United States)

    Amadio, Patrizia; Sandrini, Leonardo; Tremoli, Elena

    2017-01-01

    Brain-derived neurothrophic factor (BDNF) is a neurotrophin expressed in different tissues and cells, including neurons, endothelial cells, leukocytes, megakaryocytes and platelets. Modifications of BDNF in plasma and/or in serum are associated with neurodegenerative and psychiatric disorders, cardiovascular diseases, metabolic syndrome and with mortality risk. Indeed, changes in blood levels of BDNF may reflect those of its tissue of origin and/or promote pathological dysfunctions. The measurement of BDNF amount in plasma or in serum has been characterized with particular attention in the impact of different anti-coagulants, clotting duration, temperature (≤21 °C) and delay in blood sample centrifugation as well as in stability of storage. However, the influences of normothermic conditions (37 °C) and of clotting duration on BDNF levels in human serum have not been investigated yet. Here, we showed that time and temperature during serum preparation could be taken into consideration to assess the association and/or impact of BDNF levels in the occurrence of pathological conditions. PMID:28914800

  13. 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.

  14. 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.

  15. Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways.

    Science.gov (United States)

    Kim, Jisung; Lee, Siyoung; Choi, Bo-Ryoung; Yang, Hee; Hwang, Youjin; Park, Jung Han Yoon; LaFerla, Frank M; Han, Jung-Soo; Lee, Ki Won; Kim, Jiyoung

    2017-02-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane. Sulforaphane enhanced neuronal BDNF expression and increased levels of neuronal and synaptic molecules such as MAP2, synaptophysin, and PSD-95 in primary cortical neurons and 3 × Tg-AD mice. Sulforaphane elevated levels of synaptic TrkB signaling pathway components, including CREB, CaMKII, ERK, and Akt in both primary cortical neurons and 3 × Tg-AD mice. Sulforaphane increased global acetylation of histone 3 (H3) and H4, inhibited HDAC activity, and decreased the level of HDAC2 in primary cortical neurons. Chromatin immunoprecipitation analysis revealed that sulforaphane increased acetylated H3 and H4 at BDNF promoters, suggesting that sulforaphane regulates BDNF expression via HDAC inhibition. These findings suggest that sulforaphane has the potential to prevent neuronal disorders such as Alzheimer's disease by epigenetically enhancing neuronal BDNF expression and its TrkB signaling pathways. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

    Directory of Open Access Journals (Sweden)

    Domenico F Galati

    2016-09-01

    Full Text Available Abstract Brain-derived neurotrophic factor (BDNF regulates both action potential (AP generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function.

  17. Hypothalamic gene transfer of BDNF inhibits breast cancer progression and metastasis in middle age obese mice.

    Science.gov (United States)

    Liu, Xianglan; McMurphy, Travis; Xiao, Run; Slater, Andrew; Huang, Wei; Cao, Lei

    2014-07-01

    Activation of the hypothalamus-adipocyte axis is associated with an antiobesity and anticancer phenotype in animal models of melanoma and colon cancer. Brain-derived neurotrophic factor (BDNF) is a key mediator in the hypothalamus leading to preferential sympathoneural activation of adipose tissue and the ensuing resistance to obesity and cancer. Here, we generated middle age obese mice by high fat diet feeding for a year and investigated the effects of hypothalamic gene transfer of BDNF on a hormone receptor-positive mammary tumor model. The recombinant adeno-associated viral vector-mediated overexpression of BDNF led to marked weight loss and decrease of adiposity without change of food intake. BDNF gene therapy improved glucose tolerance, alleviated steatosis, reduced leptin level, inhibited mouse breast cancer EO771 growth, and prevented the metastasis. The reduced tumor growth in BDNF-treated mice was associated with reduced angiogenesis, decreased proliferation, increased apoptosis, and reduced adipocyte recruitment and lipid accumulation. Moreover, BDNF gene therapy reduced inflammation markers in the hypothalamus, the mammary gland, the subcutaneous fat, and the mammary tumor. Our results suggest that manipulating a single gene in the brain may influence multiple mechanisms implicated in obesity-cancer association and provide a target for the prevention and treatment of both obesity and cancer.

  18. Molecular Therapy of Melanocortin-4-Receptor Obesity by an Autoregulatory BDNF Vector

    Directory of Open Access Journals (Sweden)

    Jason J. Siu

    2017-12-01

    Full Text Available Mutations in the melanocortin-4-receptor (MC4R comprise the most common monogenic form of severe early-onset obesity, and conventional treatments are either ineffective long-term or contraindicated. Immediately downstream of MC4R—in the pathway for regulating energy balance—is brain-derived neurotrophic factor (BDNF. Our previous studies show that adeno-associated virus (AAV-mediated hypothalamic BDNF gene transfer alleviates obesity and diabetes in both diet-induced and genetic models. To facilitate clinical translation, we developed a built-in autoregulatory system to control therapeutic gene expression mimicking the body’s natural feedback systems. This autoregulatory approach leads to a sustainable plateau of body weight after substantial weight loss is achieved. Here, we examined the efficacy and safety of autoregulatory BDNF gene therapy in Mc4r heterozygous mice, which best resemble MC4R obese patients. Mc4r heterozygous mice were treated with either autoregulatory BDNF vector or YFP control and monitored for 30 weeks. BDNF gene therapy prevented the development of obesity and metabolic syndromes characterized by decreasing body weight and adiposity, suppressing food intake, alleviating hyperleptinemia and hyperinsulinemia, improving glucose and insulin tolerance, and increasing energy expenditure, without adverse cardiovascular function or behavioral disturbances. These safety and efficacy data provide preclinical evidence that BDNF gene therapy is a compelling treatment option for MC4R-deficient obese patients.

  19. Effects of soft-diet feeding on BDNF expression in hippocampus of mice.

    Science.gov (United States)

    Yamamoto, Tetsu; Hirayama, Akihiko; Hosoe, Nobuo; Furube, Masaru; Hirano, Shusuke

    2008-11-01

    Our previous study showed that mice fed a soft diet after weaning had reduced synaptic connections in the hippocampal formation and impaired spatial learning ability after 3 months of age. We hypothesized that soft-diet feeding during development reduced levels of brain-derived neurotrophic factor (BDNF) protein in the hippocampus, resulting in lower synaptic densities in this region. Male pups of C57BL/6 mice were fed either a solid (hard-diet group) or powdered diet (soft-diet group), starting at weaning. Expression of BDNF protein in the hippocampus and cerebral cortex was evaluated quantitatively with enzyme-linked immunosorbent assay (ELISA) at 1, 3 and 6 months of age. Reduction in BDNF protein levels due to soft diet was detected markedly in the hippocampus of 3- and 6-month-old mice. On the other hand, a soft diet showed no significant effect on BDNF content in the cerebral cortex throughout the ages investigated. Immunohistochemistry of hippocampal formation in 3-month-old mice revealed that intensities of BDNF immunoreactivity in the dentate gyrus granule cell layer and CA1 and CA3 pyramidal cell layers appeared diminished in mice fed the soft diet compared with mice fed the hard diet. These results indicate that insufficient mastication activity during development reduces BDNF protein levels in the hippocampus and influences synaptic plasticity in this region.

  20. Analysis of BDNF Val66Met allele-specific mRNA levels in bipolar disorder.

    Science.gov (United States)

    De Luca, Vincenzo; Strauss, John; Semeralul, Mawahib; Huang, Sheeda; Li, Peter P; Warsh, Jerry J; Kennedy, James L; Wong, Albert H C

    2008-08-22

    We have previously reported an association between the BDNF Val66Met polymorphism and bipolar disorder (BD). However, the possibility that genomic imprinting in BDNF gene affects risk for BD has not been investigated. To examine the possibility of genomic imprinting in the BDNF gene in BD, we analyzed the parent-of-origin effect (POE) and differential expression of the BDNF Val66Met alleles in BD. We performed a family-based association study and ETDT analyses of the Val66Met polymorphism in 312 BD nuclear families, and compared allele-specific mRNA levels in both post-mortem brain samples and B lymphoblasts from BD patients and controls. The BDNF Val66 allele was transmitted significantly more often to patients with BD (maternal transmissions: 46/22, p=0.003; paternal transmissions: 55/30, p=0.006). There was no significant difference between maternal and paternal transmission ratios. There was no significant difference in the ratio of Val/Met-specific mRNA expression between BD and controls, in either brain or B lymphoblasts. The Val/Met ratio was much lower in the brain vs. B lymphoblasts. These data do not support a role for genomic imprinting as a modifier of the contribution of BDNF gene to risk of susceptibility to BD.

  1. 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

    and protected against affective disorder. Whole blood assessed for BDNF concentrations and correlated to risk status, neuroticism, and number of stressful life events. RESULTS: Between the groups, we found no significant difference in whole blood BDNF levels. Women at high-risk for depression who had......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...... experienced three or more recent stressful events (n=26) had decreased whole blood BDNF levels compared to high-risk women with two or less recent stressful events (n=35), 21.6+/-7.0 vs. 18.5+/-4.1 ng/ml, respectively, (p

  2. Cardio-respiratory fitness, habitual physical activity and serum brain derived neurotrophic factor (BDNF) in men and women.

    Science.gov (United States)

    Currie, James; Ramsbottom, Roger; Ludlow, Helen; Nevill, Alan; Gilder, Michael

    2009-02-20

    Short episodes of high intensity exercise transiently increase serum levels of BDNF in humans, but serum levels of BDNF at rest appear to be lower in more physically active humans with greater levels of energy expenditure. The relationship between serum BDNF concentration, cardio-respiratory fitness (Astrand-Rhyming test estimated VO2 max) and volume of long-term, regular exercise and sporting activity (Baecke Habitual Physical Activity Index) was investigated in 44 men and women between the age range of 18-57 years. In this group an inverse relationship between resting serum BDNF concentration and measures of both estimated VO2 max (r=-0.352; Pcardio-respiratory fitness and habitual exercise are associated with lower resting levels of serum BDNF in healthy humans. This is the first study to demonstrate an inverse relationship between a physiological estimate of cardio-respiratory fitness and serum BDNF.

  3. Impacts of Carrier Transport and Deep Level Defects on Delayed Cathodoluminescence in Droop-Mitigating InGaN/GaN LEDs

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Zhibo; Singh, Akshay; Chesin, Jordan; Armitage, Rob; Wildeson, Isaac; Deb, Parijat; Armstrong, Andrew; Kisslinger, Kim; Stach, Eric; Gradecak, Silvija

    2017-07-25

    Prevalent droop mitigation strategies in InGaN-based LEDs require structural and/or compositional changes in the active region but are accompanied by a detrimental reduction in external quantum efficiency (EQE) due to increased Shockley-Read-Hall recombination. Understanding the optoelectronic impacts of structural modifications in InGaN/GaN quantum wells (QW) remains critical for emerging high-power LEDs. In this work, we use a combination of electron microscopy tools along with standard electrical characterization to investigate a wide range of low-droop InGaN/GaN QW designs. We find that chip-scale EQE is uncorrelated with extended well-width fluctuations observed in scanning transmission electron microscopy. Further, we observe delayed cathodoluminescence (CL) response from designs in which calculated band profiles suggest facile carrier escape from individual QWs. Samples with the slowest CL responses also exhibit the lowest EQEs and highest QW defect densities in deep level optical spectroscopy. We propose a model in which the electron beam (i) passivates deep level defect states and (ii) drives charge carrier accumulation and subsequent reduction of the built-in field across the multi-QW active region, resulting in delayed radiative recombination. Finally, we correlate CL rise dynamics with capacitance-voltage measurements and show that certain early-time components of the CL dynamics reflect the open circuit carrier population within one or more QWs.

  4. Coagulation defects.

    Science.gov (United States)

    Soliman, Doreen E; Broadman, Lynn M

    2006-09-01

    The present understanding of the coagulation process emphasizes the final common pathway and the proteolytic systems that result in the degradation of formed clots and the prevention of unwanted clot formations, as well as a variety of defense systems that include tissue repair, autoimmune processes, arteriosclerosis, tumor growth, the spread of metastases, and defense systems against micro-organisms. This article discusses diagnosis and management of some of the most common bleeding disorders. The goals are to provide a simple guide on how best to manage patients afflicted with congenital or acquired clotting abnormalities during the perioperative period, present a brief overview of the methods of testing and monitoring the coagulation defects, and discuss the appropriate pharmacologic or blood component therapies for each disease.

  5. A Large, Cross-sectional Observational Study of Serum BDNF, Cognitive Function, and Mild Cognitive Impairment in the Elderly

    Directory of Open Access Journals (Sweden)

    Hiroyuki eShimada

    2014-04-01

    Full Text Available Objective: The clinical relationship between brain-derived neurotrophic factor (BDNF and cognitive function or mild cognitive impairment (MCI is not well understood. The purpose of this study was to identify the relationship between serum BDNF and cognitive function and MCI, and determine whether serum BDNF level might be a useful biomarker for assessing risk for MCI in older people.Materials and Methods: A total of 4463 individuals aged 65 years or older (mean age 72 years participating in the study. We measured performance in a battery of neuropsychological and cognitive function tests; serum BDNF concentration.Results: Eight hundred twenty-seven participants (18.8% had MCI. After adjustment for sex, age, education level, diabetes, and current smoking, serum BDNF was associated with poorer performance in the story memory, and digit symbol substitution task scores. Serum BDNF was marginally associated with the presence of MCI (OR, 95% CI: 1.41, 1.00–1.99 when BDNF was 1.5 SD lower than the mean value standardized for sex and age, education level, diabetes, and current smoking.Conclusion: Low serum BDNF was associated with lower cognitive test scores and MCI. Future prospective studies should establish the discriminative value of serum BDNF for the risk of MCI.

  6. Demethylation of c-MYB binding site mediates upregulation of Bdnf IV in cocaine-conditioned place preference.

    Science.gov (United States)

    Tian, Weiping; Wang, Jiesi; Zhang, Ke; Teng, Huajing; Li, Chong; Szyf, Moshe; Sun, Zhong Sheng; Zhao, Mei

    2016-02-25

    Abnormal BDNF signaling contributes to the structural and behavioral plasticity induced by drugs of abuse. However, the mechanisms regulating expression of Bdnf in drug addiction remain elusive. In the present study, using the conditioned place preference (CPP) model, we showed that expression of Bdnf IV is upregulated in the nucleus accumbens (NAc) of conditioned animals while Bdnf I is upregulated in cocaine-treated mice irrespective of conditioning. The methylation level of a putative c-MYB binding site in the promoter region of Bdnf IV was significantly decreased in the NAc under cocaine CPP conditioning but remained unchanged without conditioning, concurrently with increased binding of c-MYB to this site. Exon IV promoter/luciferase reporter assays revealed that transactivation of Bdnf by c-MYB was blocked by methylation of this c-MYB binding site. Administration of methionine, a precursor of SAM, inhibited cocaine CPP, reversed demethylation of c-MYB binding site and induction of Bdnf IV expression by cocaine CPP. Our results imply that Bdnf IV demethylation at c-MYB binding site is involved in cocaine-triggered seeking behavior, whereas Bdnf I responds to the immediate pharmacological effects of cocaine.

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

    Directory of Open Access Journals (Sweden)

    Jun-Bin eYin

    2014-11-01

    Full Text Available 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, there still lacks detailed information on the distribution of BDNF, activation of BDNF-containing neurons projecting to RVM in the condition of pain, and neurochemical properties of these neurons within the PAG. Through fluorescent in situ hybridization (FISH and immunofluorescent staining, the homogenous distributions of BDNF mRNA and protein were observed in the four subregions of PAG. Both neurons and astrocytes expressed BDNF, but not microglias. By combining retrograde tracing methods and formalin pain model, there were more BDNF-containing neurons projecting to RVM being activated in the ventrolateral PAG (vlPAG than other subregions of PAG. The neurochemical properties of BDNF-containing projection neurons in the vlPAG were investigated. BDNF-containing projection neurons expressed auto receptor Tropomyosin-related kinase B (TrkB in addition to serotonin (5-HT, neurotensin (NT, substance P (SP, calcitonin gene related peptide (CGRP, nitric oxide synthase (NOS, and parvalbumin (PV but not tyrosine decarboxylase (TH. It is speculated that BDNF released from projection neurons in the vlPAG might participate in the descending pain modulation through enhancing the presynaptic release of other neuroactive substances (NSs in the RVM.

  8. 49 CFR 213.337 - Defective rails.

    Science.gov (United States)

    2010-10-01

    ..., due to incomplete penetration of the weld metal between the rail ends, lack of fusion between weld and... cracking. Weld defects may originate in the rail head, web, or base, and in some cases, cracks may progress... 49 Transportation 4 2010-10-01 2010-10-01 false Defective rails. 213.337 Section 213.337...

  9. 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)

  10. International conference on defects in insulating crystals

    International Nuclear Information System (INIS)

    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

  11. Prospects of Ternary Cd1-x Zn x S as an Electron Transport Layer and Associated Interface Defects in a Planar Lead Halide Perovskite Solar Cell via Numerical Simulation

    Science.gov (United States)

    Chowdhury, Towhid Hossain; Ferdaous, Mohammad Tanvirul; Wadi, Mohd. Aizat Abdul; Chelvanathan, Puvaneswaran; Amin, Nowshad; Islam, Ashraful; Kamaruddin, Nurhafiza; Zin, Muhammad Irsyamuddin M.; Ruslan, Mohd Hafidz; Sopian, Kamaruzzaman Bin; Akhtaruzzaman, Md.

    2018-03-01

    In this study we present a ternary alloy, Cd1-x Zn x S as an electron transport layer for a planar lead halide perovskite solar cell via numerical simulation with solar cell capacitance simulator (SCAPS) software. Performance dependence on molar composition variation in the Cd1-x Zn x S alloy was studied for the mixed perovskite CH3NH3PbI3-x Cl x absorber and spiro-OMeTAD hole transport material in a planar perovskite solar cell. Additionally, the defects on both Cd1-x Zn x S/CH3NH3PbI3-x Cl x and CH3NH3PbI3-x Cl x /spiro-OMeTAD interface were thoroughly investigated. Simultaneously, a thickness of 700 nm for CH3NH3PbI3-x Cl x absorber with 50-nm-thick Cd0.2Zn0.8S (x = 0.8) was optimized. Analysis of the numerical solutions via SCAPS provides a trend and pattern for Cd0.2Zn0.8S as an effective electron transport layer for planar perovskite solar cells with a yield efficiency up to 24.83%. The planar perovskite solar cell shows an open-circuit voltage of 1.224 V, short-circuit current density of 25.283 mA/cm2 and a fill factor of 80.22.

  12. Deltamethrin Increases Neurite Outgrowth in Cortical Neurons through Endogenous BDNF/TrkB Pathways.

    Science.gov (United States)

    Ihara, Daisuke; Fukuchi, Mamoru; Katakai, Momoko; Shinoda, Yo; Katoh-Semba, Ritsuko; Furuichi, Teiichi; Ishikawa, Mitsuru; Tabuchi, Akiko; Tsuda, Masaaki

    2017-10-28

    Deltamethrin (DM), a type II pyrethroid, robustly increases brain-derived neurotrophic factor (Bdnf) expression and has a neurotrophic effect in primary cultures of rat cortical neurons. In this study, we investigated the effect of DM on neurite morphology in cultured rat cortical neurons. DM significantly increased neurite outgrowth, but this increase was abolished when the BDNF scavenger tropomyosin receptor kinase B (TrkB)-Fc was added 10 min before the DM treatment. In contrast, the addition of TrkB-Fc 1 h after the treatment did not affect DM-induced neurite outgrowth. Our previous research has indicated that type II, but not type I, pyrethroids have the ability to induce Bdnf mRNA expression, but neither permethrin nor cypermethrin, which are type I and type II pyrethroids, respectively, affected neurite outgrowth in the current study. These results suggest that this effect is not due to increased Bdnf expression, and the effect is unique to DM. We previously demonstrated that calcineurin plays a role in the DM-mediated induction of Bdnf expression. However, the calcineurin inhibitor FK506 did not significantly affect DM-induced neurite outgrowth. DM-induced neurite outgrowth was abolished by U0126 and rapamycin, indicating the involvement of the mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) pathways. Taken together, these findings suggest that DM activates endogenous BDNF/TrkB-mediated MAPK and mTOR pathways, thereby increasing neurite outgrowth.Key words: BDNF, Deltamethrin, MAPK, mTOR, Neurite outgrowth.

  13. Effects of acute voluntary loaded wheel running on BDNF expression in the rat hippocampus.

    Science.gov (United States)

    Lee, Minchul; Soya, Hideaki

    2017-12-31

    Voluntary loaded wheel running involves the use of a load during a voluntary running activity. A muscle-strength or power-type activity performed at a relatively high intensity and a short duration may cause fewer apparent metabolic adaptations but may still elicit muscle fiber hypertrophy. This study aimed to determine the effects of acute voluntary wheel running with an additional load on brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus. Ten-week old male Wistar rats were assigned randomly to a (1) sedentary (Control) group; (2) voluntary exercise with no load (No-load) group; or (3) voluntary exercise with an additional load (Load) group for 1-week (acute period). The expression of BDNF genes was quantified by real-time PCR. The average distance levels were not significantly different in the No-load and Load groups. However, the average work levels significantly increased in the Load group. The relative soleus weights were greater in the No-load group. Furthermore, loaded wheel running up-regulated the BDNF mRNA level compared with that in the Control group. The BDNF mRNA levels showed a positive correlation with workload levels (r=0.75), suggesting that the availability of multiple workload levels contributes to the BDNF-related benefits of loaded wheel running noted in this study. This novel approach yielded the first set of findings showing that acute voluntary loaded wheel running, which causes muscular adaptation, enhanced BDNF expression, suggesting a possible role of high-intensity short-term exercise in hippocampal BDNF activity.

  14. Tackling Glaucoma from within the Brain: An Unfortunate Interplay of BDNF and TrkB.

    Directory of Open Access Journals (Sweden)

    Eline Dekeyster

    Full Text Available According to the neurotrophin deprivation hypothesis, diminished retrograde delivery of neurotrophic support during an early stage of glaucoma pathogenesis is one of the main triggers that induce retinal ganglion cell (RGC degeneration. Therefore, interfering with neurotrophic signaling seems an attractive strategy to achieve neuroprotection. Indeed, exogenous neurotrophin administration to the eye has been shown to reduce loss of RGCs in animal models of glaucoma; however, the neuroprotective effect was mostly insufficient for sustained RGC survival. We hypothesized that treatment at the level of neurotrophin-releasing brain areas might be beneficial, as signaling pathways activated by target-derived neurotrophins are suggested to differ from pathways that are initiated at the soma membrane. In our study, first, the spatiotemporal course of RGC degeneration was characterized in mice subjected to optic nerve crush (ONC or laser induced ocular hypertension (OHT. Subsequently, the well-known neurotrophin brain-derived neurotrophic factor (BDNF was chosen as the lead molecule, and the levels of BDNF and its high-affinity receptor, tropomyosin receptor kinase B (TrkB, were examined in the mouse retina and superior colliculus (SC upon ONC and OHT. Both models differentially influenced BDNF and TrkB levels. Next, we aimed for RGC protection through viral vector-mediated upregulation of collicular BDNF, thought to boost the retrograde neurotrophin delivery. Although the previously reported temporary neuroprotective effect of intravitreally delivered recombinant BDNF was confirmed, viral vector-induced BDNF overexpression in the SC did not result in protection of the RGCs in the glaucoma models used. These findings most likely relate to decreased neurotrophin responsiveness upon vector-mediated BDNF overexpression. Our results highlight important insights concerning the complexity of neurotrophic factor treatments that should surely be considered in

  15. BDNF genotype interacts with motor-function to influence rehabilitation responsiveness post-stroke

    Directory of Open Access Journals (Sweden)

    Christine T Shiner

    2016-05-01

    Full Text Available Background. Persistent motor impairment is common but highly heterogeneous post-stroke. Genetic polymorphisms, including those identified on the brain derived neurotrophic factor (BDNF and apolipoprotein E (APOE genes, may contribute to this variability by limiting the capacity for use-dependent neuroplasticity, and hence rehabilitation responsiveness.Objective. To determine whether BDNF and APOE genotypes influence motor improvement facilitated by post-stroke upper-limb rehabilitation. Methods. BDNF Val66Met and APOE isoform genotypes were determined using leukocyte DNA for 55 community-dwelling patients 2-123 months post-stroke. All patients completed a dose-matched upper-limb rehabilitation program of either Wii-based Movement Therapy or Constraint-induced Movement Therapy. Upper-limb motor-function was assessed pre- and post-therapy using a suite of functional measures. Results. Motor-function improved for all patients post-therapy, with no difference between therapy groups. In the pooled data, there was no significant effect of BDNF or APOE genotype on motor-function at baseline, or following the intervention. However, a significant interaction between the level of residual motor-function and BDNF genotype was identified (p=0.029, whereby post-therapy improvement was significantly less for Met allele carriers with moderate and high, but not low motor-function. There was no significant association between APOE genotype and therapy outcomes. Conclusions. This study identified a novel interaction between the BDNF Val66Met polymorphism, motor-function status and the magnitude of improvement with rehabilitation in chronic stroke. This polymorphism does not preclude, but may reduce, the magnitude of motor improvement with therapy, particularly for patients with higher but not lower residual motor-function. BDNF genotype should be considered in the design and interpretation of clinical trials.

  16. 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.

  17. Human ATP-binding cassette transporter 1 (ABC1): Genomic organization and identification of the genetic defect in the original Tangier disease kindred

    Science.gov (United States)

    Remaley, Alan T.; Rust, Stephan; Rosier, Marie; Knapper, Cathy; Naudin, Laurent; Broccardo, Cyril; Peterson, Katherine M.; Koch, Christine; Arnould, Isabelle; Prades, Catherine; Duverger, Nicholas; Funke, Harald; Assman, Gerd; Dinger, Maria; Dean, Michael; Chimini, Giovanna; Santamarina-Fojo, Silvia; Fredrickson, Donald S.; Denefle, Patrice; Brewer, H. Bryan

    1999-01-01

    Tangier disease is characterized by low serum high density lipoproteins and a biochemical defect in the cellular efflux of lipids to high density lipoproteins. ABC1, a member of the ATP-binding cassette family, recently has been identified as the defective gene in Tangier disease. We report here the organization of the human ABC1 gene and the identification of a mutation in the ABC1 gene from the original Tangier disease kindred. The organization of the human ABC1 gene is similar to that of the mouse ABC1 gene and other related ABC genes. The ABC1 gene contains 49 exons that range in size from 33 to 249 bp and is over 70 kb in length. Sequence analysis of the ABC1 gene revealed that the proband for Tangier disease was homozygous for a deletion of nucleotides 3283 and 3284 (TC) in exon 22. The deletion results in a frameshift mutation and a premature stop codon starting at nucleotide 3375. The product is predicted to encode a nonfunctional protein of 1,084 aa, which is approximately half the size of the full-length ABC1 protein. The loss of a Mnl1 restriction site, which results from the deletion, was used to establish the genotype of the rest of the kindred. In summary, we report on the genomic organization of the human ABC1 gene and identify a frameshift mutation in the ABC1 gene of the index case of Tangier disease. These results will be useful in the future characterization of the structure and function of the ABC1 gene and the analysis of additional ABC1 mutations in patients with Tangier disease. PMID:10535983

  18. Evidence of associations between brain-derived neurotrophic factor (BDNF serum levels and gene polymorphisms with tinnitus

    Directory of Open Access Journals (Sweden)

    Aysun Coskunoglu

    2017-01-01

    Full Text Available Background: Brain-derived neurotrophic factor (BDNF gene polymorphisms are associated with abnormalities in regulation of BDNF secretion. Studies also linked BDNF polymorphisms with changes in brainstem auditory-evoked response test results. Furthermore, BDNF levels are reduced in tinnitus, psychiatric disorders, depression, dysthymic disorder that may be associated with stress, conversion disorder, and suicide attempts due to crises of life. For this purpose, we investigated whether there is any role of BDNF changes in the pathophysiology of tinnitus. Materials and Methods: In this study, we examined the possible effects of BDNF variants in individuals diagnosed with tinnitus for more than 3 months. Fifty-two tinnitus subjects between the ages of 18 and 55, and 42 years healthy control subjects in the same age group, who were free of any otorhinolaryngology and systemic disease, were selected for examination. The intensity of tinnitus and depression was measured using the tinnitus handicap inventory, and the differential diagnosis of psychiatric diagnoses made using the Structured Clinical Interview for Fourth Edition of Mental Disorders. BDNF gene polymorphism was analyzed in the genomic deoxyribonucleic acid (DNA samples extracted from the venous blood, and the serum levels of BDNF were measured. One-way analysis of variance and Chi-squared tests were applied. Results: Serum BDNF level was found lower in the tinnitus patients than controls, and it appeared that there is no correlation between BDNF gene polymorphism and tinnitus. Conclusions: This study suggests neurotrophic factors such as BDNF may have a role in tinnitus etiology. Future studies with larger sample size may be required to further confirm our results.

  19. Prefrontal cortical parvalbumin and somatostatin expression and cell density increase during adolescence and are modified by BDNF and sex.

    Science.gov (United States)

    Du, X; Serena, K; Hwang, W; Grech, A M; Wu, Y W C; Schroeder, A; Hill, R A

    2018-04-01

    Brain-derived neurotrophic factor (BDNF) is known to play a critical role early in the development of cortical GABAergic interneurons. Recently our laboratory and others have shown protracted development of specific subpopulations of GABAergic interneurons extending into adolescence. BDNF expression also changes significantly across adolescent development. However the role of BDNF in regulating GABAergic changes across adolescence remains unclear. Here, we performed a week-by-week analysis of the protein expression and cell density of three major GABAergic interneurons, parvalbumin (PV), somatostatin (SST) and calretinin (Cal) in the medial prefrontal cortex from prepubescence (week 3) to adulthood (week 12). In order to assess how BDNF and sex might influence the adolescent trajectory of GABAergic interneurons we compared WT as well as BDNF heterozygous (+/-) male and female mice. In both males and females PV expression increases during adolescent development in the mPFC. Compared to wild-types, PV expression was reduced in male but not female BDNF+/- mice throughout adolescent development. This reduction in protein expression corresponded with reduced cell density, specifically within the infralimbic prefrontal cortex. SST expression increased in early adolescent WT females and this upregulation was delayed in BDNF+/-. SST cell density also increased in early adolescent mPFC of WT female mice, with BDNF+/- again showing a reduced pattern of expression. Cal protein expression was also sex-dependently altered across adolescence with WT males showing a steady decline but that of BDNF+/- remaining unaltered. Reduced cell density in on the other hand was observed particularly in male BDNF+/- mice. In females, Cal protein expression and cell density remained largely stable. Our results show that PV, SST and calretinin interneurons are indeed still developing into early adolescence in the mPFC and that BDNF plays a critical, sex-specific role in mediating expression and

  20. NGF and BDNF: from nerves to adipose tissue, from neurokines to metabokines.

    Science.gov (United States)

    Chaldakov, George N; Tonchev, Anton B; Aloe, Luigi

    2009-01-01

    Neurotrophins, particularly, NGF and BDNF are now well recognized to mediate a dizzying number of trophobiological effects, ranging from the Rita Levi-Montalcini's neurotrophic through immunotrophic to metabotrophic effects.These are implicated in the pathogenesis of various diseases including neuropsychiatric and cardiometabolic diseases, such as dementia, depression, type 2 diabetes and obesity that may express a common phenotype and coexistence. Recently, adipobiology (adiposcience) as become a focus of numerous studies showing that the adipose tissue is the body's largest endocrine organ producing multiple signaling proteins, including NGF and BDNF, all these dubbed adipokines. On the basis of our and other authors' evidence that low NGF and/or BDNF levels are found in cardiometabolic diseases (atherosclerosis, obesity, type 2 diabetes, metabolic syndrome), a hypothesis of a critical role of neuro-metabotrophic deficit in the pathogenesis of these diseases has been raised. Since NGF and BDNF also exerts various synaptotrophic effects involved in cognitive enhancement, this hypothesis might also be related to neuropsychiatric diseases such as dementia, depression, schizophrenia, autism, Rett syndrome, anorexia nervosa, and bulimia nervosa. Finally, NGF- and BDNF-based therapeutic approach, including ampakines, antidepressants, selective deacetylase inhibitors, statins, peroxisome proliferator-activated receptor gamma agonists, and "brain food" and calorie restriction, is outlined.

  1. Neuroprotection, Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration

    Directory of Open Access Journals (Sweden)

    Atsuko Kimura

    2016-09-01

    Full Text Available Neurotrophic factors play key roles in the development and survival of neurons. The potent neuroprotective effects of neurotrophic factors, including brain-derived neurotrophic factor (BDNF, ciliary neurotrophic factor (CNTF, glial cell-line derived neurotrophic factor (GDNF and nerve growth factor (NGF, suggest that they are good therapeutic candidates for neurodegenerative diseases. Glaucoma is a neurodegenerative disease of the eye that causes irreversible blindness. It is characterized by damage to the optic nerve, usually due to high intraocular pressure (IOP, and progressive degeneration of retinal neurons called retinal ganglion cells (RGCs. Current therapy for glaucoma focuses on reduction of IOP, but neuroprotection may also be beneficial. BDNF is a powerful neuroprotective agent especially for RGCs. Exogenous application of BDNF to the retina and increased BDNF expression in retinal neurons using viral vector systems are both effective in protecting RGCs from damage. Furthermore, induction of BDNF expression by agents such as valproic acid has also been beneficial in promoting RGC survival. In this review, we discuss the therapeutic potential of neurotrophic factors in retinal diseases and focus on the differential roles of glial and neuronal TrkB in neuroprotection. We also discuss the role of neurotrophic factors in neuroregeneration.

  2. A possible link between BDNF and mTOR in control of food intake

    Directory of Open Access Journals (Sweden)

    Nobuyuki eTakei

    2014-09-01

    Full Text Available Food intake is intricately regulated by glucose, amino acids, hormones, neuropeptides, and trophic factors through a neural circuit in the hypothalamus. Brain-derived neurotrophic factor (BDNF, the most prominent neurotrophic factor in the brain, regulates differentiation, maturation, and synaptic plasticity throughout life. Among its many roles, BDNF exerts an anorexigenic function in the brain. However, the intracellular signaling induced by BDNF to control food intake is not fully understood. One candidate for the molecule involved in transducing the anorexigenic activity of BDNF is the mammalian target of rapamycin (mTOR. mTOR senses extracellular amino acids, glucose, growth factors, and neurotransmitters, and regulates anabolic reactions response to these signals. Activated mTOR increases protein and lipid synthesis and inhibits protein degradation. In the hypothalamus, mTOR activation is thought to reduce food intake. Here we summarize recent findings regarding BDNF- and mTOR-mediated feeding control, and propose a link between these molecules in eating behavior.

  3. Decreased BDNF levels in amygdala and hippocampus after intracerebroventricular administration of ouabain

    Directory of Open Access Journals (Sweden)

    Luciano K. Jornada

    2012-01-01

    Full Text Available OBJECTIVE: The present study aims to investigate the effects of ouabain intracerebroventricular injection on BDNF levels in the amygdala and hippocampus of Wistar rats. METHODS: Animals received a single intracerebroventricular injection of ouabain (10-3 and 10-2 M or artificial cerebrospinal fluid and immediately, 1h, 24h, or seven days after injection, BDNF levels were measured in the rat's amygdala and hippocampus by sandwich-ELISA (n = 8 animals per group. RESULTS: When evaluated immediately, 3h, or 24h after injection, ouabain in doses of 10-2 and 10-3 M does not alter BDNF levels in the amygdala and hippocampus. However, when evaluated seven days after injection, ouabain in 10-2 and 10-3 M, showed a significant reduction in BDNF levels in both brain regions evaluated. DISCUSSION: In conclusion, we propose that the ouabain decreased BDNF levels in the hippocampus and amygdala when assessed seven days after administration, supporting the Na/K ATPase hypothesis for bipolar illness.

  4. Parent of origin effect and differential allelic expression of BDNF Val66Met in suicidal behaviour.

    Science.gov (United States)

    de Luca, Vincenzo; Souza, Renan P; Zai, Clement C; Panariello, Fabio; Javaid, Naima; Strauss, John; Kennedy, James L; Tallerico, Teresa; Wong, Albert H

    2011-02-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of mood disorders and may also be involved in suicidal behaviour since BDNF levels are decreased in brain and plasma of suicide victims. Because the differential allelic expression of Val66Met BDNF gene on suicidal behaviour has not been investigated, we analyzed the parent-of-origin effect (POE) in suicide attempters and the differential expression of BDNF Val66Met alleles in suicide victims. We performed a family-based association study and ETDT analyses of the Val66Met polymorphism in nuclear families with at least one subject affected by major psychosis with suicidal behaviour, and compared allele-specific mRNA levels in post-mortem brain samples from suicide and non-suicide victims. The subjects included in this study have diagnosis of schizophrenia, bipolar disorder type I and type II. Allele 3 in the GT repeat polymorphism was transmitted significantly more often to patients who attempted suicide (maternal transmissions: 46/22, P = 0.003; paternal transmissions: 55/30, P = 0.006). There was no significant difference between maternal and paternal transmission ratios. Furthermore, there was no significant difference in the ratio of Val/Met-specific mRNA expression between suicide victims and controls. These data do not support a role for allelic imbalance or POE of BDNF for suicidal behaviour in major psychoses.

  5. 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 B......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 BDNF Val66Met polymorphism predict onset of affective disorder in healthy individuals at heritable risk for affective disorder. In a high-risk study, we assessed whole blood levels of BDNF in 234 healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorder (high...

  6. 49 CFR 192.245 - Repair or removal of defects.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Repair or removal of defects. 192.245 Section 192.245 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF...

  7. Neural Tube Defects

    Science.gov (United States)

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

  8. Brain-derived neurotrophic factor (BDNF) serum basal levels is not affected by power training in mobility-limited older adults - A randomized controlled trial.

    Science.gov (United States)

    Hvid, L G; Nielsen, M K F; Simonsen, C; Andersen, M; Caserotti, P

    2017-07-01

    Brain-derived neurotrophic factor (BDNF) is a potential important factor involved in neuroplasticity, and may be a mediator for eliciting adaptations in neuromuscular function and physical function in older individuals following physical training. As power training taxes the neural system to a very high extent, it may be particularly effective in terms of eliciting increases in systemic BDNF levels. We examined the effects of 12weeks of power training on mature BDNF (mBDNF) and total BDNF (tBDNF) in mobility-limited older adults from the Healthy Ageing Network of Competence (HANC) study. We included 47 older men and women: n=22 in the training group (TG: progressive high intensity power training, 2 sessions per week; age 82.7±5.4years, 55% women) and n=25 in the control group (CG: no interventions; age 82.2±4.5years, 76% women). Following overnight fasting, basal serum levels of mBDNF and tBDNF were assessed (human ELISA kits) at baseline and post-intervention. At baseline, mBDNF and tBDNF levels were comparable in the two groups, TG and CG. Post-intervention, no significant within-group or between-group changes were observed in mBDNF or tBDNF. Moreover, when divided into responder tertiles based upon changes in mBDNF and tBDNF (i.e. decliners, maintainers, improvers), respectively, comparable findings were observed for TG and CG. Altogether, basal systemic levels of serum mBDNF and tBDNF are not affected in mobility-limited older adults following 12-weeks of power training, and do not appear to be a major mechanistic factor mediating neuroplasticity in mobility-limited older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis

    NARCIS (Netherlands)

    Jin, Peng; Andiappan, Anand Kumar; Quek, Jia Min; Lee, Bernett; Au, Bijin; Sio, Yang Yie; Irwanto, Astrid; Schurmann, Claudia; Grabe, Hans Joergen; Suri, Bani Kaur; Matta, Sri Anusha; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Sun, Liangdan; Zhang, Xuejun; Liu, Hong; Zhang, Furen; Larbi, Anis; Xu, Xin; Poidinger, Michael; Liu, Jianjun; Chew, Fook Tim; Rotzschke, Olaf; Shi, Li; Wang, De Yun

    Background: Brain-derived neurotrophic factor (BDNF) is a secretory protein that has been implicated in the pathogenesis of allergic rhinitis (AR), atopic asthma, and eczema, but it is currently unknown whether BDNF polymorphisms influence susceptibility to moderate-to-severe AR. Objective: We

  10. Neurogenesis Inhibition Prevents Enriched Environment to Prolong and Strengthen Social Recognition Memory, But Not to Increase BDNF Expression.

    Science.gov (United States)

    Pereira-Caixeta, Ana Raquel; Guarnieri, Leonardo O; Pena, Roberta R; Dias, Thomáz L; Pereira, Grace Schenatto

    2017-07-01

    Hippocampus-dependent memories, such as social recognition (SRM), are modulated by neurogenesis. However, the precise role of newborn neurons in social memory processing is still unknown. We showed previously that 1 week of enriched environment (EE) is sufficient to increase neurogenesis in the hippocampus (HIP) and the olfactory bulb (OB) of mice. Here, we tested the hypothesis that 1 week of EE would enhance SRM persistence and strength. In addition, as brain-derived neurotrophic factor (BDNF) may mediate some of the neurogenesis effects on memory, we also tested if 1 week of EE would increase BDNF expression in the HIP and OB. We also predicted that neurogenesis inhibition would block the gain of function caused by EE on both SRM and BDNF expression. We found that EE increased BDNF expression in the HIP and OB of mice; at the same time, it allowed SRM to last longer. In addition, mice on EE had their SRM unaffected by memory consolidation interferences. As we predicted, treatment with the anti-mitotic drug AraC blocked EE effects on SRM. Surprisingly, neurogenesis inhibition did not affect the BDNF expression, increased by EE. Together, our results suggest that newborn neurons improve SRM persistence through a BDNF-independent mechanism. Interestingly, this study on social memory uncovered an unexpected dissociation between the effect of adult neurogenesis and BDNF expression on memory persistence, reassuring the idea that not all neurogenesis effects on memory are BDNF-dependent.

  11. 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…

  12. Effect of cigarette smoke on monocyte procoagulant activity: Focus on platelet-derived brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Amadio, Patrizia; Baldassarre, Damiano; Sandrini, Leonardo; Weksler, Babette B; Tremoli, Elena; Barbieri, Silvia S

    2017-01-01

    Cigarette smoke (CS) activates platelets, promotes vascular dysfunction, and enhances Tissue Factor (TF) expression in blood monocytes favoring pro-thrombotic states. Brain-derived neurotrophic factor (BDNF), a member of the family of neurotrophins involved in survival, growth, and maturation of neurons, is released by activated platelets (APLTs) and plays a role in the cardiovascular system. The effect of CS on circulating levels of BDNF is controversial and the function of circulating BDNF in atherothrombosis is not fully understood. Here, we have shown that human platelets, treated with an aqueous extract of CS (CSE), released BDNF in a dose-dependent manner. In addition, incubation of human monocytes with BDNF or with the supernatant of platelets activated with CSE increased TF activity by a Tropomyosin receptor kinase B (TrkB)-dependent mechanism. Finally, comparing serum and plasma samples of 12 male never smokers (NS) and 29 male active smokers (AS) we observed a significant increase in microparticle-associated TF activity (MP-TF) as well as BDNF in AS, while in serum, BDNF behaved oppositely. Taken together these findings suggest that platelet-derived BDNF is involved in the regulation of TF activity and that CS plays a role in this pathway by favoring a pro-atherothrombotic state.

  13. BDNF Val66Met polymorphism as a moderator of exercise enhancement of smoking cessation treatment in anxiety vulnerable adults

    NARCIS (Netherlands)

    Smits, J.A.J.; Powers, M.B.; Rosenfield, D.; Zvolensky, M.J.; Jacquart, J.; Davis, M.L.; Beevers, C.G.; Marcus, B.H.; Church, T.S.; Otto, M.W.

    2016-01-01

    Background: Exercise interventions facilitate the odds of quit success among high-anxiety sensitive adults smokers. We examined the dependency of these benefits on the genetic BDNF Val66Met (rs6265) polymorphism; individuals who are Met carriers have lower BDNF responses and reduced associated

  14. Beneficial effect of fluoxetine treatment aganist psychological stress is mediated by increasing BDNF expression in selected brain areas.

    Science.gov (United States)

    Li, Gongying; Jing, Ping; Liu, Zhidong; Li, Zhiruo; Ma, Hongxia; Tu, Wenzhen; Zhang, Wei; Zhuo, Chuanjun

    2017-09-19

    SSRI antidepressant fluoxetine is widely used to treat psychological stress related disorders, however the underlying working mechanisms is not fully understood, as SSRIs can rapidly increase the extracellular serotonin levels but it normally takes weeks to reveal their therapeutic effect in the stress-related psychological disorders. Our previous study demonstrated that purely psychological stress without any physic stimuli induces a biphasic change in the expression of brain-derived neurotrophic factor (BDNF), which immediately decrease and then gradually increase after the stress; and that the latter BDNF increase in response to the psychological stress involves the activation of serotonin system. To investigate the role of BDNF in the fluoxetine treatment for stress-related psychological disorders, we examined the mRNA and protein levels of BDNF in the brain of Sprague-Dawley (SD) rats, which were pretreated with fluoxetine at 10 mg/kg or vehicle solution for 14 days, over 24 hour after an acute psychological stress exposure. In situ hybridization and immunohistochemistry were performed to detect the expression of BDNF at different time points in various brain regions after the psychological stress. We found that fluoxetine treatment completely blocked the BDNF decrease induced by the psychological stress, and also enhanced the gradual increase in the expression of BDNF in most of the brain regions except VTA after the psychological stress. The results suggest that the enhancement in BDNF levels induced by chronic fluoxetine treatment mediates the therapeutic effect against psychological stress.

  15. Adaptation of slow myofibers: the effect of sustained BDNF treatment of extraocular muscles in infant nonhuman primates.

    Science.gov (United States)

    Willoughby, Christy L; Fleuriet, Jérome; Walton, Mark M; Mustari, Michael J; McLoon, Linda K

    2015-06-01

    We evaluated promising new treatment options for strabismus. Neurotrophic factors have emerged as a potential treatment for oculomotor disorders because of diverse roles in signaling to muscles and motor neurons. Unilateral treatment with sustained release brain-derived neurotrophic factor (BDNF) to a single lateral rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop in correlation with extraocular muscle (EOM) changes during the critical period for development of binocularity. The lateral rectus muscles of one eye in two infant macaques were treated with sustained delivery of BDNF for 3 months. Eye alignment was assessed using standard photographic methods. Muscle specimens were analyzed to examine the effects of BDNF on the density, morphology, and size of neuromuscular junctions, as well as myofiber size. Counts were compared to age-matched controls. No change in eye alignment occurred with BDNF treatment. Compared to control muscle, neuromuscular junctions on myofibers expressing slow myosins had a larger area. Myofibers expressing slow myosin had larger diameters, and the percentage of myofibers expressing slow myosins increased in the proximal end of the muscle. Expression of BDNF was examined in control EOM, and observed to have strongest immunoreactivity outside the endplate zone. We hypothesize that the oculomotor system adapted to sustained BDNF treatment to preserve normal alignment. Our results suggest that BDNF treatment preferentially altered myofibers expressing slow myosins. This implicates BDNF signaling as influencing the slow twitch properties of EOM.

  16. BDNF-Induced Potentiation of Spontaneous Twitching in Innervated Myocytes Requires Calcium Release From Intracellular Stores

    Science.gov (United States)

    KLEIMAN, ROBIN J.; TIAN, NING; KRIZAJ, DAVID; HWANG, THOMAS N.; COPENHAGEN, DAVID R.; REICHARDT, LOUIS F.

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) can potentiate synaptic release at newly developed frog neuromuscular junctions. Although this potentiation depends on extracellular Ca2+ and reflects changes in acetylcholine release, little is known about the intracellular transduction or calcium signaling pathways. We have developed a video assay for neurotrophin-induced potentiation of myocyte twitching as a measure of potentiation of synaptic activity. We use this assay to show that BDNF-induced synaptic potentiation is not blocked by cadmium, indicating that Ca2+ influx through voltage-gated Ca2+ channels is not required. TrkB autophosphorylation is not blocked in Ca2+-free conditions, indicating that TrkB activity is not Ca2+ dependent. Additionally, an inhibitor of phospholipase C interferes with BDNF-induced potentiation. These results suggest that activation of the TrkB receptor activates phospholipase C to initiate intracellular Ca2+ release from stores which subsequently potentiates transmitter release. PMID:10899220

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

    International Nuclear Information System (INIS)

    Gai, P.L.; McCarron, E.M.; Kunchur, M.

    1991-01-01

    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

  18. Masquelet's Technique for Management of Long Bone Defects ...

    African Journals Online (AJOL)

    Bone defect, of whatever cause, is clinically challenging to treat. Defects of up to 4.0 cm can be successfully treated with cancellous bone grafting. Large defects require more complex alternatives like, bone transport, vascularized bone grafting, allografts or fibular pro-tibia grafting. There are advantages and disadvantages ...

  19. Pgrmc1/BDNF Signaling Plays a Critical Role in Mediating Glia-Neuron Cross Talk.

    Science.gov (United States)

    Sun, Fen; Nguyen, Trinh; Jin, Xin; Huang, Renqi; Chen, Zhenglan; Cunningham, Rebecca L; Singh, Meharvan; Su, Chang

    2016-05-01

    Progesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membrane-associated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted.

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

    Science.gov (United States)

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

    2011-01-01

    It has been proposed that long-term memory (LTM) 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 LTM 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 h 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. PMID:21960964

  1. Interaction between BDNF Polymorphism and Physical Activity on Inhibitory Performance in the Elderly without Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Anne Canivet

    2017-11-01

    Full Text Available Background: In the elderly, physical activity (PA enhances cognitive performances, increases brain plasticity and improves brain health. The neurotrophic hypothesis is that the release of brain-derived neurotrophic factor (BDNF, which is implicated in brain plasticity and cognition, is triggered by PA because motoneurons secrete BDNF into the bloodstream during exercise. Individual differences in cognitive performance may be explained by individual differences in genetic predisposition. A single nucleotide polymorphism on the BDNF gene, BDNFVal66Met, affects activity-dependent BDNF secretion. This study investigated the influence of the BDNFVal66Met polymorphism on the relationship between PA and controlled inhibition performance in older adults.Methods: A total of 114 healthy elderly volunteers (mean age = 71.53 years old were evaluated. Participants were genotyped for the BDNFVal66Met polymorphism. We evaluated inhibitory performance using choice reaction times (RT and error rates from a Simon-like task and estimated their PA using two self-reported questionnaires. We established four groups according to PA level (active vs. inactive and BDNFVal66Met genotype (Met carriers vs. Val-homozygous. The results were analyzed using ANOVA and ANCOVA, including age, gender and body mass index as covariates.Results: The BDNFVal66Met polymorphism interacted with PA on controlled inhibition performance. More specifically, inactive Val-homozygous participants exhibited a lower inhibition performance than active Val homozygotes and inactive Met carriers; the former had a higher error rate without differences in RT.Conclusion: Differences between individuals on inhibitory performance may be partially understood by the interaction between genetic influence in BDNF secretion and PA level. The results of this study clearly support the neurotrophic hypothesis that BDNF synthesis is an important mechanism underlying the influence of physical activity on brain

  2. Activity-Based Anorexia Alters the Expression of BDNF Transcripts in the Mesocorticolimbic Reward Circuit.

    Science.gov (United States)

    Ho, Emily V; Klenotich, Stephanie J; McMurray, Matthew S; Dulawa, Stephanie C

    2016-01-01

    Anorexia nervosa (AN) is a complex eating disorder with severe dysregulation of appetitive behavior. The activity-based anorexia (ABA) paradigm is an animal model in which rodents exposed to both running wheels and scheduled feeding develop aspects of AN including paradoxical hypophagia, dramatic weight loss, and hyperactivity, while animals exposed to only one condition maintain normal body weight. Brain-derived neurotrophic factor (BDNF), an activity-dependent modulator of neuronal plasticity, is reduced in the serum of AN patients, and is a known regulator of feeding and weight maintenance. We assessed the effects of scheduled feeding, running wheel access, or both on the expression of BDNF transcripts within the mesocorticolimbic pathway. We also assessed the expression of neuronal cell adhesion molecule 1 (NCAM1) to explore the specificity of effects on BDNF within the mesocorticolimbic pathway. Scheduled feeding increased the levels of both transcripts in the hippocampus (HPC), increased NCAM1 mRNA expression in the ventral tegmental area (VTA), and decreased BDNF mRNA levels in the medial prefrontal cortex (mPFC). In addition, wheel running increased BDNF mRNA expression in the VTA. No changes in either transcript were observed in the nucleus accumbens (NAc). Furthermore, no changes in either transcript were induced by the combined scheduled feeding and wheel access condition. These data indicate that scheduled feeding or wheel running alter BDNF and NCAM1 expression levels in specific regions of the mesocorticolimbic pathway. These findings contribute to our current knowledge of the molecular alterations induced by ABA and may help elucidate possible mechanisms of AN pathology.

  3. 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

  4. BDNF and BMI effects on brain structures of bipolar offspring: results from the global mood and brain science initiative.

    Science.gov (United States)

    Mansur, R B; Brietzke, E; McIntyre, R S; Cao, B; Lee, Y; Japiassú, L; Chen, K; Lu, R; Lu, W; Li, T; Xu, G; Lin, K

    2017-12-01

    To compare brain-derived neurotrophic factor (BDNF) levels between offspring of individuals with bipolar disorders (BD) and healthy controls (HCs) and investigate the effects of BDNF levels and body mass index (BMI) on brain structures. Sixty-seven bipolar offspring and 45 HCs were included (ages 8-28). Structural images were acquired using 3.0 Tesla magnetic resonance imaging. Serum BDNF levels were measured using enzyme-linked immunosorbent assay. Multivariate and univariate analyses of covariance were conducted. Significantly higher BDNF levels were observed among bipolar offspring, relative to HCs (P > 0.025). Offspring status moderated the association between BDNF and BMI (F 1 =4.636, P = 0.034). After adjustment for relevant covariates, there was a trend for a significant interaction of group and BDNF on neuroimaging parameters (Wilks'λ F 56,94 =1.463, P = 0.052), with significant effects on cerebellar white matter and superior and middle frontal regions. Brain volume and BDNF were positively correlated among HCs and negatively correlated among bipolar offspring. Interactions between BDNF and BMI on brain volumes were non-significant among HCs (Wilks'λ F 28,2 =2.229, P = 0.357), but significant among bipolar offspring (Wilks'λ F 28,12 =2.899, P = 0.028). Offspring status and BMI moderate the association between BDNF levels and brain structures among bipolar offspring, underscoring BDNF regulation and overweight/obesity as key moderators of BD pathogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF and oxytocin receptor (OXTR genes are associated with anxiety/depression in older women

    Directory of Open Access Journals (Sweden)

    Yvon eChagnon

    2015-06-01

    Full Text Available Background: Environmental effects and personal experiences could be expressed in individuals through epigenetic non-structural changes such as DNA methylation. This methylation could up- regulate or down-regulate corresponding gene expressions and modify related phenotypes. DNA methylation increases with ageing and could be related to the late expression of some forms of mental disease. The objective of this study was to evaluate the association between anxiety disorders and/or depression in older women and DNA methylation for four genes related to anxiety or depression. Methods: Women aged 65 and older with (n =19 or without (n =24 anxiety disorders and/or major depressive episode (DSM-IV, were recruited. DNA methylation and single nucleotide variant (SNV were evaluated from saliva, respectively by pyrosequencing and by PCR, for the following genes: brain-derived neurotrophic factor (BDNF; rs6265, oxytocin receptor (OXTR; rs53576, serotonin transporter (SLC6A4; rs25531 and apolipoprotein E (APOE; rs429358 and rs7412. Results: A greater BDNF DNA methylation was observed in subjects with anxiety/depression compared to control group subjects(Mean: 2.92 SD: 0.74 vs. 2.34 SD: 0.42; p=0.0026.This difference was more pronounced in subjects carrying the BDNF rs6265 CT genotype (2.99 SD: 0.41 vs.2.27 SD: 0.26; p=0.0006 than those carrying the CC genotype (p=0.0332; no subjects with the TT genotype were observed. For OXTR, a greater DNA methylation was observed in subjects with anxiety/depression, but only for those carrying the AA genotype of the OXTR rs53576SNV, more particularly at one out of the seven CpGs studied (7.01 SD: 0.94 vs. 4.44 SD: 1.11; p=0.0063. No significant differences were observed for APOE and SLC6A4.Conclusion: These results suggest that DNA methylation in interaction with SNV variations in BDNF and OXTR, are associated with the occurrence of anxiety/depression in older women.

  6. 49 CFR 215.121 - Defective car body.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defective car body. 215.121 Section 215.121..., 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...

  7. 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 a...

  8. Lipid Absorption Defects in Intestine-specific Microsomal Triglyceride Transfer Protein and ATP-binding Cassette Transporter A1-deficient Mice*

    Science.gov (United States)

    Iqbal, Jahangir; Parks, John S.; Hussain, M. Mahmood

    2013-01-01

    We have previously described apolipoprotein B (apoB)-dependent and -independent cholesterol absorption pathways and the role of microsomal triglyceride transfer protein (MTP) and ATP-binding cassette transporter A1 (ABCA1) in these pathways. To assess the contribution of these pathways to cholesterol absorption and to determine whether there are other pathways, we generated mice that lack MTP and ABCA1, individually and in combination, in the intestine. Intestinal deletions of Mttp and Abca1 decreased plasma cholesterol concentrations by 45 and 24%, respectively, whereas their combined deletion reduced it by 59%. Acute cholesterol absorption was reduced by 28% in the absence of ABCA1, and it was reduced by 92–95% when MTP was deleted in the intestine alone or together with ABCA1. MTP deficiency significantly reduced triglyceride absorption, although ABCA1 deficiency had no effect. ABCA1 deficiency did not affect cellular lipids, but Mttp deficiency significantly increased intestinal levels of triglycerides and free fatty acids. Accumulation of intestinal free fatty acids, but not triglycerides, in Mttp-deficient intestines was prevented when mice were also deficient in intestinal ABCA1. Combined deficiency of these genes increased intestinal fatty acid oxidation as a consequence of increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and carnitine palmitoyltransferase 1α (CPT1α). These studies show that intestinal MTP and ABCA1 are critical for lipid absorption and are the main determinants of plasma and intestinal lipid levels. Reducing their activities might lower plasma lipid concentrations. PMID:24019513

  9. Tranquilizing and Allaying Excitement Needling Method Affects BDNF and SYP Expression in Hippocampus

    Directory of Open Access Journals (Sweden)

    Peng Zheng

    2017-01-01

    Full Text Available Sleep disorder is a state of sleep loss caused by various reasons, which leads to a series of changes, such as emotion, learning and memory, and immune function. “Tranquilizing and allaying excitement” was widely used in clinical treatment of insomnia; however, the mechanism was still not very clear. We randomly divided rats into three groups: control group, sleep deprivation group, and acupuncture treatment group. We observed BDNF and SYP expression in hippocampus in these three groups. Both protein contents and mRNA contents of BDNF and SYP were measured by western blot, immunohistochemistry, and RT-PCR analysis. The sleep deprivation model was established using modified multiple platform sleep deprivation method (MMPM. Our study explored the BDNF and SYP abnormality in hippocampus caused by sleep deprivation and “tranquilizing and allaying excitement” intervention regulated the abnormal expression of BDNF and SYP caused by sleep deprivation on the short run and the long run. Our study provided a molecular evidence that “tranquilizing and allaying excitement” treatment in rats with sleep disorder affects learning and memory ability.

  10. The role of BDNF, leptin, and catecholamines in reward learning in bulimia nervosa.

    Science.gov (United States)

    Homan, Philipp; Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Eckert, Anne; Lang, Undine; Hasler, Gregor

    2014-12-07

    A relationship between bulimia nervosa and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Using a randomized, double-blind, placebo-controlled, crossover design, a reward learning task was applied to study the behavior of 20 female subjects with remitted bulimia nervosa and 27 female healthy controls under placebo and catecholamine depletion with alpha-methyl-para-tyrosine (AMPT). The plasma levels of BDNF and leptin were measured twice during the placebo and the AMPT condition, immediately before and 1 hour after a standardized breakfast. AMPT-induced differences in plasma BDNF levels were positively correlated with the AMPT-induced differences in reward learning in the whole sample (P=.05). Across conditions, plasma brain derived neurotrophic factor levels were higher in remitted bulimia nervosa subjects compared with controls (diagnosis effect; P=.001). Plasma BDNF and leptin levels were higher in the morning before compared with after a standardized breakfast across groups and conditions (time effect; Pbulimia nervosa and controls. A role of leptin in reward learning is not supported by this study. However, leptin levels were sensitive to a depletion of catecholamine stores in both remitted bulimia nervosa and controls. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  11. 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

    , and health indicators in a statistical model. In the present study the serum BDNF levels were increased in the depressive subjects compared to control individuals. Additionally, six SNPs were successfully analyzed, but did not associate with depression. Multiple linear regression models were applied and age...

  12. Neuroplasticity and memory formation in major depressive disorder: an imaging genetics perspective on serotonin and BDNF.

    Science.gov (United States)

    Kuhn, Manuel; Popovic, Ana; Pezawas, Lukas

    2014-01-01

    A vast number of imaging studies have demonstrated the impact of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) on emotion and memory-related networks in the context of Major Depressive Disorder (MDD). Underlying molecular mechanisms that affect the functionality of these networks have been examined in detail in animals and corroborate imaging findings. The crucial role of 5-HT and BDNF signaling in the context of MDD is reflected in the etiologic models of MDD such as the monoamine or neuroplasticity hypothesis as well as in pharmacological models of antidepressant response. While antidepressant drug treatment has been primarily linked to the modulation of emotion-related networks, cognitive behavioral therapy has been implicated in a top-down control of limbic structures. Initially, a simple lack of monoamines or BDNF has been proposed as causal factor of MDD etiology. However, recent findings suggest a much more complex neurobiology emphasizing epistatic and epigenetic mechanisms responsible for structural and functional changes observed in emotion and memory-related brain regions of healthy subjects and MDD patients. In this review, which focuses on neuroimaging studies in the context of MDD, the authors will provide a comprehensive overview of these networks as well as on the specific role of 5-HT and BDNF in their development and function.

  13. Age-related changes in plasma levels of BDNF in Down syndrome patients

    Directory of Open Access Journals (Sweden)

    Licastro Federico

    2010-01-01

    Full Text Available 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: the first consisted of 23 children (age 2-14 years; the second of 14 adults (age 20-50 years, the third group of 13 elderly persons (>60 years and a controls group of 20 healthy patients (age 15-60 years. The analytes of interest were quantified using a biochip array analyzer (Evidence®, Randox Ltd., Crumlin, UK. Results Plasma BDNF was higher in DS patients than in controls and there was a significant age-related increase. Serum levels of IL-6 and MCP-1 were also higher in DS children and adults, but not in older patients, than in healthy control. High levels of circulating BDNF may protect DS patients from the clinical complications of atherosclerosis. However, the striking drop in peripheral BDNF levels with age might predispose these patients to clinical manifestations of dementia in later life.

  14. BDNF (brain-derived neurotrophic factor) serum levels in schizophrenic patients with cognitive deficits

    Science.gov (United States)

    Utami, N.; Effendy, E.; Amin, M. M.

    2018-03-01

    Schizophrenia is a complex neurodevelopmental disorder with cognitive impairment as the main part. BDNF regulates aspects of developmental plasticity in the brain and is involved in cognitive function. Cognitive functions include capabilities such as attention, executive functioning, assessing, monitoring and evaluating. The aim of the study was to know the BDNF levels in schizophrenic patients with cognitive deficits. The study was held in October 2016 - March 2017, and was the first in Indonesia, especially in North Sumatra. The study was approved by the medical ethics committee of the University of North Sumatera. The study is descriptive based on a retrospective method with cross-sectional approach. The subject is 40 male schizophrenia. Cognitive deficits were assessed by MoCA-Ina. BDNF serum levels were analyzed using the quantitative sandwich enzyme immunoassay. The average MoCA-Ina score is 21.03±5.21. This suggests that there is a cognitive function deficit in schizophrenic patients. The mean serum BDNF level was 26629±6762. MoCA-Ina scores in schizophrenic patients values ranging from 6.186 to 42.580pg/ml.

  15. The vagus nerve modulates BDNF expression and neurogenesis in the hippocampus.

    Science.gov (United States)

    O'Leary, Olivia F; Ogbonnaya, Ebere S; Felice, Daniela; Levone, Brunno R; C Conroy, Lorraine; Fitzgerald, Patrick; Bravo, Javier A; Forsythe, Paul; Bienenstock, John; Dinan, Timothy G; Cryan, John F

    2018-02-01

    Accumulating evidence suggests that certain gut microbiota have antidepressant-like behavioural effects and that the microbiota can regulate neurogenesis and the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. The precise mechanisms underlying these effects are not yet clear. However, the vagus nerve is one of the primary bidirectional routes of communication between the gut and the brain and thus may represent a candidate mechanism. Yet, relatively little is known about the direct influence of vagus nerve activity on hippocampal function and plasticity. Thus, the aim of the present study was to determine whether constitutive vagus nerve activity contributes to the regulation of neurogenesis and BDNF mRNA expression in the hippocampus. To this end, we examined the impact of subdiaphragmatic vagotomy in adult mice on these parameters. We found that vagotomy decreased BDNF mRNA in all areas of the hippocampus. Vagotomy also reduced the proliferation and survival of newly born cells and decreased the number of immature neurons, particularly those with a more complex dendritic morphology. Taken together, these findings suggest that vagal nerve activity influences neurogenesis and BDNF mRNA expression in the adult hippocampus. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  16. Cannabis use, COMT, BDNF and age at first-episode psychosis.

    Science.gov (United States)

    Mané, Anna; Bergé, Daniel; Penzol, Maria Jose; Parellada, Mara; Bioque, Miquel; Lobo, Antonio; González-Pinto, Ana; Corripio, Iluminada; Cabrera, Bibiana; Sánchez-Torres, Ana Maria; Saiz-Ruiz, Jerónimo; Bernardo, Miguel

    2017-04-01

    Although an interaction between COMT Val158Met and BDNF Val66Met polymorphisms with cannabis use has been proposed with respect to the risk of psychosis emergence, findings remain inconclusive. The aim of the present study was to evaluate the different possible associations between these polymorphisms and early cannabis use and the age at the first episode of psychosis. The relationship between age at psychosis onset and COMT Val158Met and BDNF Val66Met polymorphisms with early cannabis use as well as those factors associated with early cannabis use were investigated. Among 260 Caucasian first-episode psychosis patients, early cannabis use and the presence of the met-allele from the BDNF Val66Met polymorphism were significantly associated with age at psychosis onset. Furthermore, early cannabis use was significantly associated with male gender in the logistic regression analysis. These findings provide evidence of the important role of early cannabis use and the Val66Met BDNF polymorphism on age at psychosis onset and they point out to sex-specific differences in cannabis use patterns. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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

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    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.

  18. Dean vortex membrane microfiltration and diafiltration of rBDNF E. coli inclusion bodies

    NARCIS (Netherlands)

    Schutyser, M.A.I.; Rupp, R.; Wideman, J.; Belfort, G.

    2002-01-01

    Cross-flow microfiltration (CMF) and diafiltration were used to concentrate and purify recombinant Brain-Derived Neutrophic Factor (rBDNF) inclusion bodies from an E. coli cell suspension and a homogenized E. coli cell suspension (homogenate/lysate). Although these processes have been tested

  19. The role of brain-derived neurotrophic factor (BDNF in comorbid depression: possible linkage with steroid hormones, cytokines, and nutrition

    Directory of Open Access Journals (Sweden)

    Tadahiro eNumakawa

    2014-09-01

    Full Text Available Increasing evidence demonstrates a connection between growth factor function (including brain-derived neurotrophic factor, BDNF, glucocorticoid levels (one of the steroid hormones, and the pathophysiology of depressive disorders. Because both BDNF and glucocorticoids regulate synaptic function in the central nervous system, their functional interaction is of major concern. Interestingly, alterations in levels of estrogen, another steroid hormone, may play a role in depressive-like behavior in postpartum females with fluctuations of BDNF-related molecules in the brain. BDNF and cytokines, which are protein regulators of inflammation, stimulate multiple intracellular signaling cascades involved in neuropsychiatric illness. Pro-inflammatory cytokines may increase vulnerability to depressive symptoms, such as the increased risk observed in patients with cancer and/or autoimmune diseases. In this review, we discuss the possible relationship between inflammation and depression, in addition to the crosstalk among cytokines, BDNF and steroids. Further, since nutritional status has been shown to affect critical pathways involved in depression through both BDNF function and the monoamine system, we also review current evidence surrounding diet and supplementation (e.g., flavonoids on BDNF-mediated brain functions.

  20. The functional BDNF Val66Met polymorphism affects functions of pre-attentive visual sensory memory processes.

    Science.gov (United States)

    Beste, Christian; Schneider, Daniel; Epplen, Jörg T; Arning, Larissa

    2011-01-01

    The brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is involved in nerve growth and survival. Especially, a single nucleotide polymorphism (SNP) in the BDNF gene, Val66Met, has gained a lot of attention, because of its effect on activity-dependent BDNF secretion and its link to impaired memory processes. We hypothesize that the BDNF Val66Met polymorphism may have modulatory effects on the visual sensory (iconic) memory performance. Two hundred and eleven healthy German students (106 female and 105 male) were included in the data analysis. Since BDNF is also discussed to be involved in the pathogenesis of depression, we additionally tested for possible interactions with depressive mood. The BDNF Val66Met polymorphism significantly influenced iconic-memory performance, with the combined Val/Met-Met/Met genotype group revealing less time stability of information stored in iconic memory than the Val/Val group. Furthermore, this stability was positively correlated with depressive mood exclusively in the Val/Val genotype group. Thus, these results show that the BDNF Val66Met polymorphism has an effect on pre-attentive visual sensory memory processes. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Repeated social defeat and the rewarding effects of cocaine in adult and adolescent mice: dopamine transcription factors, proBDNF signaling pathways, and the TrkB receptor in the mesolimbic system.

    Science.gov (United States)

    Montagud-Romero, Sandra; Nuñez, Cristina; Blanco-Gandia, M Carmen; Martínez-Laorden, Elena; Aguilar, María A; Navarro-Zaragoza, Javier; Almela, Pilar; Milanés, Maria-Victoria; Laorden, María-Luisa; Miñarro, José; Rodríguez-Arias, Marta

    2017-07-01

    Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents. The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice. Male adolescent and young adult OF1 mice were exposed to four episodes of social defeat and were conditioned 3 weeks later with 1 mg/kg of cocaine. In a second set of mice, the expressions of the abovementioned dopaminergic and proBDNF and TrkB receptor were measured in VTA and NAc, respectively. Adolescent mice experienced social defeats less intensely than their adult counterparts and produced lower levels of corticosterone. However, both adult and adolescent defeated mice developed conditioned place preference for the compartment associated with this low dose of cocaine. Furthermore, only adolescent defeated mice displayed diminished levels of the transcription factors Pitx3 in the VTA, without changes in the expression of DAT and D2DR in the NAc. In addition, stressed adult mice showed a decreased expression of proBDNF and the TrkB receptor, while stressed adolescent mice exhibited increased expression of latter without changes in the former. Our findings suggest that dopaminergic pathways and proBDNF signaling and TrkB receptors play different roles in social defeat-stressed mice exposed to cocaine.

  2. Associations between parenting behavior and anxiety in a rodent model and a clinical sample: relationship to peripheral BDNF levels

    Science.gov (United States)

    Dalle Molle, R; Portella, A K; Goldani, M Z; Kapczinski, F P; Leistner-Segala, S; Salum, G A; Manfro, G G; Silveira, P P

    2012-01-01

    Adverse early-life environment is associated with anxiety-like behaviors and disorders. Brain-derived neurotrophic factor (BDNF) is sensitive to this environment and could be a marker of underlying brain changes. We aimed at evaluating the development of anxiety-like behaviors in a rat model of early adversity, as well as the possible association with BDNF levels. Similar associations were investigated in a sample of adolescent humans. For the rat study, Wistar rat litters were divided into: early-life stress (ELS, limited access to nesting material) and control groups. Maternal behavior was observed from days 1 to 9 of life and, as adults, rats were subjected to behavioral testing and BDNF measurements in plasma, hippocampus, amygdala and periaqueductal gray. For the human study, 129 adolescents were evaluated for anxiety symptoms and perceived parental care. Serum BDNF levels and the Val66Met polymorphism of the BDNF gene were investigated. We found that ELS dams showed more pure contact, that is, contact with low care and high control, toward pups, and their adult offspring demonstrated higher anxiety-like behaviors and plasma BDNF. Also the pure contact correlated positively with adult peripheral BDNF. Similarly in humans, there was a positive correlation between maternal overprotection and serum BDNF only in Met carriers. We also found negative correlations between maternal warmth and separation anxiety, social phobia and school phobia. Finally, our translational approach revealed that ELS, mediated through variations in maternal care, is associated with anxiety in both rats and humans and increased peripheral BDNF may be marking these phenomena. PMID:23168995

  3. The BDNF Val66Met Polymorphism Affects the Vulnerability of the Brain Structural Network

    Directory of Open Access Journals (Sweden)

    Chang-hyun Park

    2017-08-01

    Full Text Available Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF gene resulting in a valine (Val to methionine (Met substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes (n = 18 and Met-allele carriers (n = 55. Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity.

  4. Childhood trauma interacted with BDNF Val66Met influence schizophrenic symptoms.

    Science.gov (United States)

    Bi, Xiao-Jiao; Lv, Xiao-Min; Ai, Xian-Ying; Sun, Meng-Meng; Cui, Kai-Yan; Yang, Li-Min; Wang, Li-Na; Yin, Ai-Hua; Liu, Lan-Fen

    2018-03-01

    The gene - environment (G × E) interaction effect is involved in severe mental disorders. However, whether the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism participates in the childhood-abuse influenced schizophrenic symptoms remains unclear. We examined the interaction between BDNF Val66Met, and childhood trauma (ChT) on psychotic symptoms in a Chinese Han population.To estimate the G × E interaction, psychiatric interviews, self-report questionnaires for ChT, and genotyping for BDNF Val66Met were carried out on 201 schizophrenic patients. G × E interactions were analyzed by generalized multifactor dimensionality reduction (GMDR).Among all patients, 11.9%, 19.4%, 23.4%, 26.4%, and 73.6% reported emotional abuses, physical abuses (PA), sexual abuses (SA), emotional neglects (EN), and physical neglects (PN), respectively. Significant negative correlations were observed between anxiety/depression factors, and ChT total scores. Patients with 3 different BDNF genotypes showed significant differences in anxiety/depression scores. Significant 2-way interactions were found for Val66Met × PN, 3-way interactions were found for Val66Met × PN × PA, and four-way interactions were found for Val66Met × PN × PA × EN with regard to the excitement scores.Our findings suggested an involvement of BDNF Val66Met polymorphism after ChT in terms of risk for schizophrenia symptoms.

  5. BDNF Val66Met Polymorphism Interacts with Sleep Consolidation to Predict Ability to Create New Declarative Memories.

    Science.gov (United States)

    Gosselin, Nadia; De Beaumont, Louis; Gagnon, Katia; Baril, Andrée-Ann; Mongrain, Valérie; Blais, Hélène; Montplaisir, Jacques; Gagnon, Jean-François; Pelleieux, Sandra; Poirier, Judes; Carrier, Julie

    2016-08-10

    It is hypothesized that a fundamental function of sleep is to restore an individual's day-to-day ability to learn and to constantly adapt to a changing environment through brain plasticity. Brain-derived neurotrophic factor (BDNF) is among the key regulators that shape brain plasticity. However, advancing age and carrying the BDNF Met allele were both identified as factors that potentially reduce BDNF secretion, brain plasticity, and memory. Here, we investigated the moderating role of BDNF polymorphism on sleep and next-morning learning ability in 107 nondemented individuals who were between 55 and 84 years of age. All subjects were tested with 1 night of in-laboratory polysomnography followed by a cognitive evaluation the next morning. We found that in subjects carrying the BDNF Val66Val polymorphism, consolidated sleep was associated with significantly better performance on hippocampus-dependent episodic memory tasks the next morning (β-values from 0.290 to 0.434, p ≤ 0.01). In subjects carrying at least one copy of the BDNF Met allele, a more consolidated sleep was not associated with better memory performance in most memory tests (β-values from -0.309 to -0.392, p values from 0.06 to 0.15). Strikingly, increased sleep consolidation was associated with poorer performance in learning a short story presented verbally in Met allele carriers (β = -0.585, p = 0.005). This study provides new evidence regarding the interacting roles of consolidated sleep and BDNF polymorphism in the ability to learn and stresses the importance of considering BDNF polymorphism when studying how sleep affects cognition. Individuals with the BDNF Val/Val (valine allele) polymorphism showed better memory performance after a night of consolidated sleep. However, we observed that middle-aged and older individuals who are carriers of the BDNF Met allele displayed no positive association between sleep quality and their ability to learn the next morning. This interaction between sleep and

  6. [Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behavior efficacy].

    Science.gov (United States)

    Firstova, Iu Iu; Dolotov, O V; Kondrakhin, e A; Dubynina, E V; Grivennikov, I A; Kovalev, G I

    2009-01-01

    The influence of subchronic administration of nootropic drugs (piracetam, phenotropil, meclophenoxate, pantocalcine, semax, nooglutil) on the brain-derived neurotrophic factor (BDNF) content in hippocampal and cortical tissues in mice with different exploratory behavior--high efficacy (HE) against low efficacy (LE)--in cross-maze test has been studied. The initial BDNF concentration in hippocamp (but not in cortex) of control HE mice was higher than that in LE mice (LE, 0.091 +/- 0.005 pg/microg; HE, 0.177 +/- 0.005 pg/microg; p nootrope effects, at least partially, via increase in hippocampal BDNF level, which is achieved only under conditions of cognitive deficiency.

  7. 49 CFR 195.230 - Welds: Repair or removal of defects.

    Science.gov (United States)

    2010-10-01

    ... TRANSPORTATION OF HAZARDOUS LIQUIDS BY PIPELINE Construction § 195.230 Welds: Repair or removal of defects. (a... 49 Transportation 3 2010-10-01 2010-10-01 false Welds: Repair or removal of defects. 195.230 Section 195.230 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND...

  8. 49 CFR 215.103 - Defective wheel.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defective wheel. 215.103 Section 215.103... § 215.103 Defective wheel. A railroad may not place or continue in service a car, if— (a) A wheel flange... tread of the wheel; (b) The height of a wheel flange on the car, from the tread to the top of the flange...

  9. A flavonoid agonist of the TrkB receptor for BDNF improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn mouse model of DS.

    Science.gov (United States)

    Stagni, Fiorenza; Giacomini, Andrea; Guidi, Sandra; Emili, Marco; Uguagliati, Beatrice; Salvalai, Maria Elisa; Bortolotto, Valeria; Grilli, Mariagrazia; Rimondini, Roberto; Bartesaghi, Renata

    2017-12-01

    Intellectual disability is the unavoidable hallmark of Down syndrome (DS), with a heavy impact on public health. Reduced neurogenesis and impaired neuron maturation are considered major determinants of altered brain function in DS. Since the DS brain starts at a disadvantage, attempts to rescue neurogenesis and neuron maturation should take place as soon as possible. The brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain development by specifically binding to tropomyosin-related kinase receptor B (TrkB). Systemic BDNF administration is impracticable because BDNF has a poor blood-brain barrier penetration. Recent screening of a chemical library has identified a flavone derivative, 7,8-dihydroxyflavone (7,8-DHF), a small-molecule that crosses the blood-brain barrier and binds with high affinity and specificity to the TrkB receptor. The therapeutic potential of TrkB agonists for neurogenesis improvement in DS has never been examined. The goal of our study was to establish whether it is possible to restore brain development in the Ts65Dn mouse model of DS by targeting the TrkB receptor with 7,8-DHF. Ts65Dn mice subcutaneously injected with 7,8-DHF in the neonatal period P3-P15 exhibited a large increase in the number of neural precursor cells in the dentate gyrus and restoration of granule cell number, density of dendritic spines and levels of the presynaptic protein synaptophysin. In order to establish the functional outcome of treatment, mice were treated with 7,8-DHF from P3 to adolescence (P45-50) and were tested with the Morris Water Maze. Treated Ts65Dn mice exhibited improvement of learning and memory, indicating that the recovery of the hippocampal anatomy translated into a functional rescue. Our study in a mouse model of DS provides novel evidence that treatment with 7,8-DHF during the early postnatal period restores the major trisomy-linked neurodevelopmental defects, suggesting that therapy with 7,8-DHF may represent a

  10. Defect of the Eyelids.

    Science.gov (United States)

    Lu, Guanning Nina; Pelton, Ron W; Humphrey, Clinton D; Kriet, John David

    2017-08-01

    Eyelid defects disrupt the complex natural form and function of the eyelids and present a surgical challenge. Detailed knowledge of eyelid anatomy is essential in evaluating a defect and composing a reconstructive plan. Numerous reconstructive techniques have been described, including primary closure, grafting, and a variety of local flaps. This article describes an updated reconstructive ladder for eyelid defects that can be used in various permutations to solve most eyelid defects. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Stress-induced change in serum BDNF is related to quantitative family history of alcohol use disorder and age at first alcohol use.

    Science.gov (United States)

    Sharma, Shobhit; Graham, Reiko; Rohde, Rodney; Ceballos, Natalie A

    2017-02-01

    Previous research in animal models suggests that brain-derived neurotrophic factor (BDNF) is involved in stress-modulated alcohol consumption. However, relatively few studies have investigated this issue in humans, and results of existing studies have been heterogeneous. The primary aim of the current study was to examine the within-subjects effect of acute stress (timed math plus cold pressor) on serum BDNF levels (ΔBDNF: post- minus pre-stress) in healthy social drinkers (N=68, 20 male). A secondary aim was to explore which heritable and environmental factors in our limited sample might exert the greatest influences on ΔBDNF. Importantly, presence versus absence of the BDNF Val 66 Met polymorphism (rs6265), which has often been discounted in studies of human serum BDNF, was included as a between-subjects control variable in all statistical analyses. Our results indicated that acute stress decreased serum BDNF. Further, multiple regression analyses revealed that quantitative family history of alcohol use disorder (qFH) and age at first alcohol use together accounted for 15% of the variance in ΔBDNF. Thus, the influences of qFH and age at first alcohol use may explain some of the heterogeneity that exists in previous studies of human serum BDNF. These results parallel findings in animal models and suggest that stress-related changes in serum BDNF are influenced by both heritable (qFH) and environmental (early alcohol consumption) factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment.

    Science.gov (United States)

    Rodier, Marion; Quirié, Aurore; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2015-01-01

    The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels.

  13. Cross-sex hormone treatment in male-to-female transsexual persons reduces serum brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

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

    2015-01-01

    Serum levels of brain-derived neurotrophic factor (BDNF) are reduced in male-to-female transsexual persons (MtF) compared to male controls. It was hypothesized before that this might reflect either an involvement of BDNF in a biomechanism of transsexualism or to be the result of persistent social stress due to the condition. Here, we demonstrate that 12 month of cross-sex hormone treatment reduces serum BDNF levels in male-to-female transsexual persons independent of anthropometric measures. Participants were acquired through the European Network for the Investigation of Gender Incongruence (ENIGI). Reduced serum BDNF in MtF thus seems to be a result of hormonal treatment rather than a consequence or risk factor of transsexualism. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  14. Reciprocal Regulation of Very Low Density Lipoprotein Receptors (VLDLRs) in Neurons by Brain-derived Neurotrophic Factor (BDNF) and Reelin

    Science.gov (United States)

    Do, Hai Thi; Bruelle, Céline; Tselykh, Timofey; Jalonen, Pilvi; Korhonen, Laura; Lindholm, Dan

    2013-01-01

    BDNF positively influences various aspects of neuronal migration, maturation, and survival in the developing brain. Reelin in turn mediates inhibitory signals to migrating neuroblasts, which is crucial for brain development. The interplay between BDNF and Reelin signaling in neurodevelopment is not fully understood. We show here that BDNF increased the levels of the Reelin receptor (VLDL receptor (VLDLR)) in hippocampal neurons by increasing gene expression. In contrast, Reelin decreased VLDLRs, which was accompanied by an increase in the levels of the E3 ligase Mylip/Idol in neurons. Down-regulation of Mylip/Idol using shRNAs abrogated the decrease in VLDLRs induced by Reelin. These results show that VLDLRs are tightly regulated in hippocampal neurons by both transcriptional and post-transcriptional mechanisms. The regulation of VLDLR by BDNF and Reelin may affect the migration of neurons and contribute to neurodevelopmental disorders in the nervous system. PMID:23990472

  15. BDNF activates mTOR to regulate GluR1 expression required for memory formation.

    Directory of Open Access Journals (Sweden)

    Leandro Slipczuk

    Full Text Available BACKGROUND: The mammalian target of Rapamycin (mTOR kinase plays a key role in translational control of a subset of mRNAs through regulation of its initiation step. In neurons, mTOR is present at the synaptic region, where it modulates the activity-dependent expression of locally-translated proteins independently of mRNA synthesis. Indeed, mTOR is necessary for different forms of synaptic plasticity and long-term memory (LTM formation. However, little is known about the time course of mTOR activation and the extracellular signals governing this process or the identity of the proteins whose translation is regulated by this kinase, during mnemonic processing. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that consolidation of inhibitory avoidance (IA LTM entails mTOR activation in the dorsal hippocampus at the moment of and 3 h after training and is associated with a rapid and rapamycin-sensitive increase in AMPA receptor GluR1 subunit expression, which was also blocked by intra-hippocampal delivery of GluR1 antisense oligonucleotides (ASO. In addition, we found that pre- or post-training administration of function-blocking anti-BDNF antibodies into dorsal CA1 hampered IA LTM retention, abolished the learning-induced biphasic activation of mTOR and its readout, p70S6K and blocked GluR1 expression, indicating that BDNF is an upstream factor controlling mTOR signaling during fear-memory consolidation. Interestingly, BDNF ASO hindered LTM retention only when given into dorsal CA1 1 h after but not 2 h before training, suggesting that BDNF controls the biphasic requirement of mTOR during LTM consolidation through different mechanisms: an early one involving BDNF already available at the moment of training, and a late one, happening around 3 h post-training that needs de novo synthesis of this neurotrophin. CONCLUSIONS/SIGNIFICANCE: IN CONCLUSION, OUR FINDINGS DEMONSTRATE THAT: 1 mTOR-mediated mRNA translation is required for memory consolidation during

  16. Brain-Derived Neurotrophic Factor (BDNF) protein levels in anxiety disorders: systematic review and meta-regression analysis

    Science.gov (United States)

    Suliman, Sharain; Hemmings, Sian M. J.; Seedat, Soraya

    2013-01-01

    Background: Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that is involved in the synaptic plasticity and survival of neurons. BDNF is believed to be involved in the pathogenesis of several neuropsychiatric disorders. As findings of BDNF levels in anxiety disorders have been inconsistent, we undertook to conduct a systematic review and meta-analysis of studies that assessed BDNF protein levels in these disorders. Methods: We conducted the review using electronic databases and searched reference lists of relevant articles for any further studies. Studies that measured BDNF protein levels in any anxiety disorder and compared these to a control group were included. Effect sizes of the differences in BDNF levels between anxiety disorder and control groups were calculated. Results: Eight studies with a total of 1179 participants were included. Initial findings suggested that BDNF levels were lower in individuals with any anxiety disorder compared to those without [Standard Mean Difference (SMD) = −0.94 (−1.75, −0.12), p ≤ 0.05]. This was, however, dependent on source of BDNF protein [plasma: SMD = −1.31 (−1.69, −0.92), p ≤ 0.01; serum: SMD = −1.06 (−2.27, 0.16), p ≥ 0.01] and type of anxiety disorder [PTSD: SMD = −0.05 (−1.66, 1.75), p ≥ 0.01; OCD: SMD = −2.33 (−4.21, −0.45), p ≤ 0.01]. Conclusion: Although BDNF levels appear to be reduced in individuals with an anxiety disorder, this is not consistent across the various anxiety disorders and may largely be explained by the significantly lowered BDNF levels found in OCD. Results further appear to be mediated by differences in sampling methods. Findings are, however, limited by the lack of research in this area, and given the potential for BDNF as a biomarker of anxiety disorders, it would be useful to clarify the relationship further. PMID:23908608

  17. Plasticity after pediatric cochlear implantation: Implication from changes in peripheral plasma level of BDNF and auditory nerve responses.

    Science.gov (United States)

    Alemi, Razieh; Motassadi Zarandy, Masoud; Joghataei, Mohammad Taghi; Eftekharian, Ali; Zarrindast, Mohammad Reza; Vousooghi, Nasim

    2018-02-01

    Sensory neural hearing loss could lead to some structural and physiological changes in the auditory pathways, such as alteration in the expression of neurotrophins. These factors, especially Brain-Derived Neurotrophic Factor (BDNF), play an important role in synaptic functions and experience-related plasticity. Restoring cochlear function after hearing loss is possible through cochlear implantation (CI). Evaluation of the blood concentration changes of neurotrophins as prerequisites of plasticity could help scientists to determine the prognosis of CI as in the candidacy procedure or enhancing prosthesis function by adding the exact needed amount of BDNF to the electrode array. Here we have studied the plasma BDNF concentration before CI surgery and 6 months after using CI device in 15 pediatric CI recipients and compared this level with changes of BDNF concentration in 10 children who were using hearing aid (H.A). In addition, we searched for a possible correlation between post-surgery plasma BDNF concentration and electrical compound action potential (ECAP) and comfort-level (C-level) thresholds. Plasma BDNF concentration in children with CI increased significantly after CI surgery, while this difference in H.A group was not significant. Analysis of repeated measures of ECAP and C-level thresholds in CI group showed that there were some kinds of steadiness during follow- up sessions for ECAP thresholds in basal and E16 of middle electrodes, whereas C-level thresholds for all selected electrodes increased significantly up to six months follow-up. Interestingly, we did not find any significant correlation between post-surgery plasma BDNF concentration and ECAP or C-level threshold changes. It is concluded that changes in C-level threshold and steady state of ECAP thresholds and significant changes in BDNF concentration could be regarded as an indicator of experienced-related plasticity after CI stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. BDNF Val66Met Polymorphism Interacts with Sleep Consolidation to Predict Ability to Create New Declarative Memories

    Science.gov (United States)

    Gosselin, Nadia; De Beaumont, Louis; Gagnon, Katia; Baril, Andrée-Ann; Mongrain, Valérie; Blais, Hélène; Montplaisir, Jacques; Gagnon, Jean-François; Pelleieux, Sandra; Poirier, Judes; Carrier, Julie

    2016-01-01

    It is hypothesized that a fundamental function of sleep is to restore an individual’s day-to-day ability to learn and to constantly adapt to a changing environment through brain plasticity. Brain-derived neurotrophic factor (BDNF) is among the key regulators that shape brain plasticity. However, advancing age and carrying the BDNF Met allele were both identified as factors that potentially reduce BDNF secretion, brain plasticity, and memory. Here, we investigated the moderating role of BDNF polymorphism on sleep and next-morning learning ability in 107 nondemented individuals who were between 55 and 84 years of age. All subjects were tested with 1 night of in-laboratory polysomnography followed by a cognitive evaluation the next morning. We found that in subjects carrying the BDNF Val66Val polymorphism, consolidated sleep was associated with significantly better performance on hippocampus-dependent episodic memory tasks the next morning (β-values from 0.290 to 0.434, p ≤ 0.01). In subjects carrying at least one copy of the BDNF Met allele, a more consolidated sleep was not associated with better memory performance in most memory tests (β-values from −0.309 to −0.392, p values from 0.06 to 0.15). Strikingly, increased sleep consolidation was associated with poorer performance in learning a short story presented verbally in Met allele carriers (β = −0.585, p = 0.005). This study provides new evidence regarding the interacting roles of consolidated sleep and BDNF polymorphism in the ability to learn and stresses the importance of considering BDNF polymorphism when studying how sleep affects cognition. PMID:27511011

  19. Brain derived Neurotropic Factor (BDNF) is associated with childhood abuse but not cognitive domains in first episode psychosis.

    Science.gov (United States)

    Theleritis, Christos; Fisher, Helen L; Shäfer, Ingo; Winters, Laura; Stahl, Daniel; Morgan, Craig; Dazzan, Paola; Breedvelt, Josefien; Sambath, Irene; Vitoratou, Silia; Russo, Manuela; Reichenberg, Abraham; Falcone, M Aurora; Mondelli, Valeria; O'Connor, Jennifer; David, Anthony; McGuire, Philip; Pariante, Carmine; Di Forti, Marta; Murray, Robin M; Bonaccorso, Stefania

    2014-10-01

    The Brain-derived Neurotrophic Factor (BDNF) modulates cognitive processes and is associated with increased risk of schizophrenia. Childhood trauma (CT) is frequent in patients with psychosis and severely affects course and outcome. We investigated the hypothesis that BDNF is associated with both CT and cognitive deficits in a sample of first-episode psychosis (FEP) cases and unaffected controls. Participants with FEP and healthy controls were recruited between August 2008 and July 2011 from South London, UK. Childhood traumatic events were detected using the Childhood Experience of Care and Abuse Questionnaire (CECA-Q). Neuropsychological data were also collected. BDNF plasma levels were measured from fasting blood samples. Data were available on 87 FEP patients and 152 controls. Our results showed a significant effect of separation (F=5.5; df=1,115; p=.02), physical (F=4.7; df=1, 118; p=.03) and sexual abuse (F=5.4; df=1,117; p=.02) on BDNF levels with lower levels among those who experienced the traumatic event compared to those who did not. Physical abuse predicted lower plasma levels of BDNF (β=-.30; p=.03) whereas sexual and/or physical abuse showed a trend (β=-.26; p=.06) in FEP patients but not in unaffected controls. No association between BDNF plasma levels and cognitive functions was found among patients with FEP and controls. Our findings suggest the possible involvement of BDNF in the onset of first-episode psychosis in individuals exposed to early trauma and propose BDNF as a potential clinical biomarker to detect the detrimental effects of CT on human brain plasticity. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  20. The role of the BDNF Val66Met polymorphism in individual differences in long-term memory capacity.

    Science.gov (United States)

    Montag, Christian; Felten, Andrea; Markett, Sebastian; Fischer, Luise; Winkel, Katja; Cooper, Andrew; Reuter, Martin

    2014-12-01

    The protein brain-derived neurotrophic factor (BDNF) plays an important role in diverse memory processes and is strongly expressed in the hippocampus. The hippocampus itself is a key structure involved in the processing of information from short-term to long-term memory. Due to the putative role of BDNF in memory consolidation, a prominent single nucleotide polymorphism (SNP) on the BDNF gene (BDNF Val66Met) was investigated in the context of long-term memory performance. N=138 students were presented with 40 words from 10 categories, each consisting of eight words such as 'fruits' or 'vehicles' in a memory recognition task (specifically the Deese-Roediger-McDermott Paradigm). Recognition performance was analyzed 25 min after the initial presentation of the word list and subsequently 1 week after the initial presentation. Overall, individual long-term memory performance immediately after learning the word list (T1) and performance 1 week later (T2) did not differ on the basis of the BDNF SNP, but an interaction effect of BDNF Val66Met by time-of-recall was found: Carriers of the Met66+ variant showed the strongest decline in hit rate performance over time.

  1. 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.

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

    International Nuclear Information System (INIS)

    Halepoto, D.M.; Bashir, S.

    2015-01-01

    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)

  3. Stability of BDNF in Human Samples Stored Up to 6 Months and Correlations of Serum and EDTA-Plasma Concentrations.

    Science.gov (United States)

    Polyakova, Maryna; Schlögl, Haiko; Sacher, Julia; Schmidt-Kassow, Maren; Kaiser, Jochen; Stumvoll, Michael; Kratzsch, Jürgen; Schroeter, Matthias L

    2017-06-03

    Brain-derived neurotrophic factor (BDNF), an important neural growth factor, has gained growing interest in neuroscience, but many influencing physiological and analytical aspects still remain unclear. In this study we assessed the impact of storage time at room temperature, repeated freeze/thaw cycles, and storage at -80 °C up to 6 months on serum and ethylenediaminetetraacetic acid (EDTA)-plasma BDNF. Furthermore, we assessed correlations of serum and plasma BDNF concentrations in two independent sets of samples. Coefficients of variations (CVs) for serum BDNF concentrations were significantly lower than CVs of plasma concentrations ( n = 245, p = 0.006). Mean serum and plasma concentrations at all analyzed time points remained within the acceptable change limit of the inter-assay precision as declared by the manufacturer. Serum and plasma BDNF concentrations correlated positively in both sets of samples and at all analyzed time points of the stability assessment ( r = 0.455 to r s = 0.596; p plasma up to 6 months. Due to a higher reliability, we suggest favoring serum over EDTA-plasma for future experiments assessing peripheral BDNF concentrations.

  4. 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

    2015-01-02

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. 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.

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

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    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.

  7. On holographic defect entropy

    Energy Technology Data Exchange (ETDEWEB)

    Estes, John [Blackett Laboratory, Imperial College,London SW7 2AZ (United Kingdom); Jensen, Kristan [Department of Physics and Astronomy, University of Victoria,Victoria, BC V8W 3P6 (Canada); C.N. Yang Institute for Theoretical Physics, SUNY Stony Brook,Stony Brook, NY 11794-3840 (United States); O’Bannon, Andy [Rudolf Peierls Centre for Theoretical Physics, University of Oxford,1 Keble Road, Oxford OX1 3NP (United Kingdom); Tsatis, Efstratios [8 Kotylaiou Street, Athens 11364 (Greece); Wrase, Timm [Stanford Institute for Theoretical Physics, Stanford University,Stanford, CA 94305 (United States)

    2014-05-19

    We study a number of (3+1)- and (2+1)-dimensional defect and boundary conformal field theories holographically dual to supergravity theories. In all cases the defects or boundaries are planar, and the defects are codimension-one. Using holography, we compute the entanglement entropy of a (hemi-)spherical region centered on the defect (boundary). We define defect and boundary entropies from the entanglement entropy by an appropriate background subtraction. For some (3+1)-dimensional theories we find evidence that the defect/boundary entropy changes monotonically under certain renormalization group flows triggered by operators localized at the defect or boundary. This provides evidence that the g-theorem of (1+1)-dimensional field theories generalizes to higher dimensions.

  8. On holographic defect entropy

    Science.gov (United States)

    Estes, John; Jensen, Kristan; O'Bannon, Andy; Tsatis, Efstratios; Wrase, Timm

    2014-05-01

    We study a number of (3 + 1)- and (2 + 1)-dimensional defect and boundary conformal field theories holographically dual to supergravity theories. In all cases the defects or boundaries are planar, and the defects are codimension-one. Using holography, we compute the entanglement entropy of a (hemi-)spherical region centered on the defect (boundary). We define defect and boundary entropies from the entanglement entropy by an appropriate background subtraction. For some (3 + 1)-dimensional theories we find evidence that the defect/boundary entropy changes monotonically under certain renormalization group flows triggered by operators localized at the defect or boundary. This provides evidence that the g-theorem of (1 + 1)-dimensional field theories generalizes to higher dimensions.

  9. NMR backbone resonance assignments of the prodomain variants of BDNF in the urea denatured state.

    Science.gov (United States)

    Wang, Jing; Bains, Henrietta; Anastasia, Agustin; Bracken, Clay

    2018-04-01

    Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family of proteins which plays a central role in neuronal survival, growth, plasticity and memory. A single Val66Met variant has been identified in the prodomain of human BDNF that is associated with anxiety, depression and memory disorders. The structural differences within the full-length prodomain Val66 and Met66 isoforms could shed light on the mechanism of action of the Met66 and its impact on the development of neuropsychiatric-associated disorders. In the present study, we report the backbone 1 H, 13 C, and 15 N NMR assignments of both full-length Val66 and Met66 prodomains in the presence of 2 M urea. These conditions were utilized to suppress residual structure and aid subsequent native state structural investigations aimed at mapping and identifying variant-dependent conformational differences under native-state conditions.

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

    Directory of Open Access Journals (Sweden)

    Rodrigo eNieto

    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.

  11. Extreme ultraviolet multilayer defect analysis and geometry reconstruction

    Science.gov (United States)

    Xu, Dongbo; Evanschitzky, Peter; Erdmann, Andreas

    2016-01-01

    This paper proposes a method for the characterization of multilayer defects from extreme ultraviolet (EUV) projection images at different focus positions. The transport-of-intensity equation is applied to retrieve the phase distribution of the reflected light in the vicinity of the defect. The defect-induced intensity and phase modifications and their dependency from defect geometry parameters are analyzed by several selected optical properties of multilayer defect. To reconstruct the defect geometry parameters from the intensity and phase of a defect, a principal component analysis (PCA) is employed to parameterize the intensity and phase distributions into principal component coefficients. In order to construct the base functions of the PCA, a combination of a reference multilayer defect and appropriate pupil filters is introduced to obtain the designed sets of intensity and phase distributions. Finally, an artificial neural network is applied to correlate the principal component coefficients of the intensity and the phase of the defect with the defect geometry parameters and to reconstruct the unknown defect geometry parameters. The performance of the proposed approach is evaluated both for mask blank defects and for defects in the vicinity of an absorber pattern.

  12. Early Stress Evokes Age-Dependent Biphasic Changes in Hippocampal Neurogenesis, Bdnf Expression, and Cognition

    Science.gov (United States)

    Suri, Deepika; Veenit, Vandana; Sarkar, Ambalika; Thiagarajan, Devi; Kumar, Arvind; Nestler, Eric J.; Galande, Sanjeev; Vaidya, Vidita A.

    2014-01-01

    Background Adult-onset stressors exert opposing effects on hippocampal neurogenesis and cognition, with enhancement observed following mild stress and dysfunction following severe chronic stress. While early life stress evokes persistent changes in anxiety, it is unknown whether early stress differentially regulates hippocampal neurogenesis, trophic factor expression, and cognition across the life span. Methods Hippocampal-dependent cognitive behavior, neurogenesis, and epigenetic regulation of brain-derived neurotrophic factor (Bdnf) expression was examined at distinct time points across the life span in rats subjected to the early stress of maternal separation (ES) and control groups. We also examined the influence of chronic antidepressant treatment on the neurogenic, neurotrophic, and cognitive changes in middle-aged ES animals. Results Animals subjected to early stress of maternal separation examined during postnatal life and young adulthood exhibited enhanced hippocampal neurogenesis, decreased repressive histone methylation at the Bdnf IV promoter along with enhanced Bdnf levels, and improved performance on the stress-associated Morris water maze. Strikingly, opposing changes in hippocampal neurogenesis and epigenetic regulation of Bdnf IV expression, concomitant with impairments on hippocampal-dependent cognitive tasks, were observed in middle-aged ES animals. Chronic antidepressant treatment with amitriptyline attenuated the maladaptive neurogenic, epigenetic, transcriptional, and cognitive effects in middle-aged ES animals. Conclusions Our study provides novel insights into the short- and long-term consequences of ES, demonstrating both biphasic and unique, age-dependent changes at the molecular, epigenetic, neurogenic, and behavioral levels. These results indicate that early stress may transiently endow animals with a potential adaptive advantage in stressful environments but across a life span is associated with long-term deleterious effects. PMID

  13. Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF

    OpenAIRE

    Graybeal, Carolyn; Feyder, Michael; Schulman, Emily; Saksida, Lisa M.; Bussey, Timothy J.; Brigman, Jonathan L.; Holmes, Andrew

    2011-01-01

    Stress often has deleterious effects on cognition. We show that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task. Ventromedial prefrontal cortex (vmPFC) lesions mimicked the effects of stress, while orbitofrontal (OFC) and dorsolateral striatal (DLS) lesions impaired reversal. Stress-facilitation of reversal was prevented by BDNF infusion into the vmPFC. These findings suggest a mechanism in which stress-induced vmPFC dysfunction disinhibits learning by...

  14. TBARS and BDNF levels in newborns exposed to crack/cocaine during pregnancy: a comparative study

    Directory of Open Access Journals (Sweden)

    Victor Mardini

    2017-03-01

    Full Text Available Objectives: To compare levels of a marker of lipid peroxidation (thiobarbituric acid reactive substances, TBARS and brain-derived neurotrophic factor (BDNF in umbilical cord blood (UCB between newborns exposed to crack/cocaine in utero (exposed newborns [EN], n=57 and non-exposed newborns (NEN, n=99, as well as in maternal peripheral blood at delivery. Methods: This was a cross-sectional study. Potential confounders, including perinatal parameters, psychopathology, and use of other substances, were assessed. Results: After adjusting for potential confounders, adjusted mean BDNF was significantly higher in EN (3.86 ng/mL, 95% confidence interval [95%CI] 2.29-5.43 than in NEN (0.85 ng/mL, 95%CI 0.47-1.23; p < 0.001; Cohen effect size: 1.12, and significantly lower in crack/cocaine mothers than in control mothers (4.03 ng/mL, 95%CI 2.87-5.18 vs. 6.67 ng/mL, 95%CI 5.60-7.74; p = 0.006. The adjusted mean TBARS level was significantly lower in EN (63.97 µM MDA, 95%CI 39.43-88.50 than NEN (177.04 µM MDA, 95%CI 140.93-213.14; p < 0.001; effect size = 0.84, with no difference between mother groups (p = 0.86. Conclusions: The changes in TBARS levels observed in EN suggest that fetuses exposed to cocaine mobilize endogenous antioxidant routes since very early stages of development. The increase in BDNF levels in EN might indicate changes in fetal development, whereas the changes in BDNF levels in mothers provide evidence of the complex metabolic processes involved in drug use during pregnancy.

  15. Suppression of choriocarcinoma invasion and metastasis following blockade of BDNF/TrkB signaling

    International Nuclear Information System (INIS)

    Kawamura, Kazuhiro; Kawamura, Nanami; Okamoto, Naoki; Manabe, Motomu

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) acts through its cognate receptor tyrosine kinase-B (TrkB) to regulate diverse physiological functions in reproductive and other tissues. In normal and malignant trophoblastic cells, the BDNF/TrkB signaling promotes cell growth. Due to the highly malignant nature of choriocarcinoma, we investigated possible involvement of this system in choriocarcinoma cell invasion and metastasis. We demonstrated that treatment of cultured choriocarcinoma cells, known to express both BDNF and TrkB, with a soluble TrkB ectodomain or a Trk receptor inhibitor K252a suppressed cell invasion accompanied with decreased expression of matrix metalloproteinase-2, a cell invasion marker. In vivo studies using a tumor xenograft model in athymic nude mice further showed inhibition of cell invasion from tumors to surrounding tissues following the suppression of endogenous TrkB signaling. For an in vivo model of choriocarcinoma metastasis, we performed intravenous injections of JAR cells expressing firefly luciferase into severe combined immunodeficiency (SCID) mice. Treatment with K252a inhibited metastasis of tumors to distant organs. In vivo K252a treatment also suppressed metastatic tumor growth as reflected by decreased cell proliferation and increased apoptosis and caspases-3/7 activities, together with reduced tissue levels of a tumor marker, human chorionic gonadotropin-β. In vivo suppression of TrkB signaling also led to decreased expression of angiogenic markers in metastatic tumor, including cluster of differentiation 31 and vascular endothelial growth factor A. Our findings suggested essential autocrine/paracrine roles of the BDNF/TrkB signaling system in choriocarcinoma invasion and metastasis. Inhibition of this signaling could serve as the basis to develop a novel therapy for patients with choriocarcinoma

  16. Effects of different timing of stress on corticosterone, BDNF and memory in male rats.

    Science.gov (United States)

    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

    2015-02-01

    Learning and memory seem to be affected by chronic stress. Previous reports have considered chronic stress as a precipitating factor of different neuropsychological disorders, while others reported neurobiological adaptations following stress. The present study investigated the effects of chronic stress before, after, and during learning on the changes of learning and memory, on serum and hippocampal levels of corticosterone (CORT), brain-derived neurotrophic factor (BDNF) and body weight in rats. Male Wistar rats were randomly divided into four groups (n=10) including Control (Co), Stress-Learning-Rest (St-L-Re), Rest-Learning-Stress (Re-L-St), and Stress-Learning-Stress (St-L-St) groups. The chronic restraint stress was applied 6 h/day for 21 days. Moreover, the passive avoidance test was used to assess memory deficit, 1, 7, and 21 days after training. At the end of experiments, CORT and BDNF levels were measured. The findings did not support adaptation in chronic stress conditions. The acquisition time as well as the short and mid-term memories was significantly impaired in the St-L-Re group. Short, mid, and long-term memories were significantly impaired in the Re-L-St and St-L-St groups compared with the Co group, as a result of the enhancement of CORT and reduction of BDNF levels. In the St-L-St group, changes in memory functions were less pronounced than in the Re-L-St group. Also, body weight declined following the chronic stress, while recovery period enhanced the body weight gain in stressed rats. It can be concluded that a potential time-dependent involvement of stress and recovery period on the level of BDNF. Longer duration time of chronic stress might promote adaptive effects on memory and CORT level. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

    Directory of Open Access Journals (Sweden)

    Kaja K Jasińska

    Full Text Available 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.

  18. BDNF levels are associated with autistic traits in the general population.

    Science.gov (United States)

    Brondino, Natascia; Fusar-Poli, Laura; Rocchetti, Matteo; Bertoglio, Federico; Bloise, Nora; Visai, Livia; Politi, Pierluigi

    2018-03-01

    Evidence supports the notion that autistic symptoms and behaviors should be regarded as dimensional traits. The present study aimed to investigate the role of vasopressin (AVP), brain-derived neurotrophic factor (BDNF) and oxytocin (OXT) as potential biochemical correlates of subclinical autistic traits in a cohort of healthy young adults. One hundred and fifty-three subjects (80 males, 73 females) were recruited. Participants completed the Autism Spectrum Quotient (AQ), a widely used measure for the identification of autistic traits in the general population. Additionally, blood samples were obtained from all participants at the same time of the day to control for circadian variation. We conducted a multiple regression analysis using the AQ score as the dependent variable and age, sex, AVP, BDNF and OXT levels as the independent variables. The model explained approximately the 22% of the variance of the AQ score. Among the parameters included in the analysis, only BDNF levels were independent predictors of AQ score. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Differential effects of BDNF val(66)met in repetitive associative learning paradigms.

    Science.gov (United States)

    Freundlieb, Nils; Backhaus, Winifried; Brüggemann, Norbert; Gerloff, Christian; Klein, Christine; Pinnschmidt, Hans O; Hummel, Friedhelm C

    2015-09-01

    In healthy young subjects, the brain derived neurotropic factor (BDNF) val(66)met polymorphism negatively affects behavioural outcome in short-term motor cortex or hippocampus-based learning paradigms. In repetitive training paradigms over several days this effect can be overcome, in tests involving other brain areas even positive effects were found. To further specify the role of this polymorphism in cognitive processes, we used an associative vocabulary learning paradigm over four consecutive days and tested 38 young healthy subjects and 29 healthy elderly subjects. As a control paradigm, we designed a nonverbal haptic Braille letter-learning paradigm based on the same principles. Behavioural outcome was then associated with the BDNF-genotype. In the vocabulary learning task, met carrier (met/val and met/met) benefitted more from the repetitive training than val/val subjects. This was paralleled by a higher reduction of delayed answers during the course of the study, an effect that was also present in the haptic paradigm. However, in a group of healthy elderly subjects, no similar tendency was found. We conclude that the BDNF val(66)met polymorphism alters highly circumscribed answer behaviours in young healthy subjects. This might partly explain the high variability of previously published results. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults

    Directory of Open Access Journals (Sweden)

    Kirsten Hötting

    2016-01-01

    Full Text Available In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans.

  1. The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults.

    Science.gov (United States)

    Hötting, Kirsten; Schickert, Nadine; Kaiser, Jochen; Röder, Brigitte; Schmidt-Kassow, Maren

    2016-01-01

    In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans.

  2. 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 hypoc......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 serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher...

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

    Directory of Open Access Journals (Sweden)

    Wenjuan Yu

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

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

    Science.gov (United States)

    Yu, Wenjuan; Zhu, Hao; Wang, Yueming; Li, Guanjun; Wang, Lihua; Li, Huafang

    2015-01-01

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

  5. Peptides derived from the solvent-exposed loops 3 and 4 of BDNF bind TrkB and p75(NTR) receptors and stimulate neurite outgrowth and survival

    DEFF Research Database (Denmark)

    Fobian, Kristina; Owczarek, Sylwia; Budtz, Christian

    2010-01-01

    . BDNF has been implicated in several neurological disorders, and irregularities in BDNF function may have severe consequences. Administration of BDNF as a drug has thus far yielded few practicable results, and the potential side effects when using a multifunctional protein are substantial. In an effort......), and induced neurite outgrowth and enhanced neuronal survival, probably by inducing signaling through tha Akt and MAPK pathways. Distinct, charged residues within the Betrofin sequences were identified as important for generating the neuritogenic response, which was also inhibited when BDNF was added together...

  6. 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.

  7. 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.

  8. Local and nonlocal defect-mediated electroweak baryogenesis

    International Nuclear Information System (INIS)

    Brandenberger, R.; Davis, A.; Prokopec, T.; Trodden, M.

    1996-01-01

    We consider the effects of particle transport in topological defect-mediated electroweak baryogenesis scenarios. We analyze the cases of both thin and thick defects and demonstrate an enhancement of the original mechanism in both cases due to an increased effective volume in which baryogenesis occurs. This phenomenon is a result of an imperfect cancellation between the baryons and antibaryons produced on opposite faces of the defect. copyright 1996 The American Physical Society

  9. ROLE OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF IN THE DIAGNOSIS OF COGNTIVE DYSFUNCTION IN PATIENTS WITH TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    Irina Vladimirovna Gatskikh

    2016-02-01

    Full Text Available One of the heavy progressive vascular complications of type 2 diabetes is a central nervous system, manifesting cognitive dysfunction due to metabolic changes. Goal. Defining the role of brain-derived neurotrophic factor (BDNF in the diagnosis of cognitive dysfunction in patients with type 2 diabetes. Materials and methods. The study involved 83 patients with type 2 diabetes at the age of 40 - 70 years. Complex examination included clinical and laboratory examination, neuropsychological testing. To screen for cognitive impairment used the Montreal Cognitive Assessment Scale (MOS test. To identify early markers of cognitive impairment was determined the level of brain-derived neurotrophic factor (BDNF. Results. The study found a negative correlation between the level of BDNF and the HbA1c (r = - 0,494, p = 0.01, fasting glucose (r = - 0,499, p = 0.01, and a positive relationship between the level of BDNF and cognitive function in patients with type 2 diabetes. Conclusion. In patients with type 2 diabetes revealed cognitive dysfunction in the form of reduced memory, attention, optical-dimensional activity that correlated with chronic hyperglycemia. The role of brain-derived neurotrophic factor (BDNF in the complex diagnosis of cognitive dysfunction in patients with type 2 diabetes. With an increase in HbA1c in patients with type 2 diabetes reduces the level of BDNF in the blood plasma, and a decline in cognitive function. Recommended use of BDNF as an additional marker of cognitive dysfunction in patients with type 2 diabetes.

  10. Prenatal auditory stimulation alters the levels of CREB mRNA, p-CREB and BDNF expression in chick hippocampus.

    Science.gov (United States)

    Chaudhury, Sraboni; Wadhwa, Shashi

    2009-10-01

    Prenatal auditory stimulation influences the development of the chick auditory pathway and the hippocampus showing an increase in various morphological parameters as well as expression of calcium-binding proteins. Calcium regulates the activity of cyclic adenosine monophosphate-response element binding (CREB) protein. CREB is known to play a role in development, undergo phosphorylation with neural activity as well as regulate transcription of BDNF. BDNF is important for the survival of neurons and regulates synaptic strength. Hence in the present study, we have evaluated the levels of CREB mRNA and protein along with p-CREB protein as well as BDNF mRNA and protein levels in the chick hippocampus at embryonic days (E) 12, E16, E20 and post-hatch day (PH) 1 following activation by prenatal auditory stimulation. Fertilized eggs were exposed to species-specific sound or sitar music (frequency range: 100-6300Hz) at 65dB levels for 15min/h over 24h from E10 till hatching. The control chick hippocampus showed higher CREB mRNA and p-CREB protein in the early embryonic stages, which later decline whereas BDNF mRNA and BDNF protein levels increase until PH1. The CREB mRNA and p-CREB protein were significantly increased at E12, E16 and PH1 in the auditory stimulated groups as compared to control group. A significant increase in the level of BDNF mRNA was observed from E12 and the protein expression from E16 onwards in both auditory stimulated groups. Therefore, enhanced phosphorylation of CREB during development following prenatal sound stimulation may be responsible for cell survival. Increased levels of p-CREB again at PH1 may trigger synthesis of proteins necessary for synaptic plasticity. Further, the increased levels of BDNF may also help in regulating synaptic plasticity.

  11. Atorvastatin Protects from Aβ1-40-Induced Cell Damage and Depressive-Like Behavior via ProBDNF Cleavage.

    Science.gov (United States)

    Ludka, Fabiana K; Cunha, Maurício P; Dal-Cim, Tharine; Binder, Luisa Bandeira; Constantino, Leandra C; Massari, Caio M; Martins, Wagner C; Rodrigues, Ana Lúcia S; Tasca, Carla I

    2017-10-01

    Intracerebroventricular (icv) amyloid-beta (Aβ) 1-40 infusion to mice has been demonstrated to cause neurotoxicty and depressive-like behavior and it can be used to evaluate antidepressant and neuroprotective effect of drugs. Atorvastatin is a widely used statin that has demonstrated antidepressant-like effect in predictable animal behavioral models and neuroprotective effect against Aβ 1-40 infusion. The purpose of this study was to determine the effect of in vivo atorvastatin treatment against Aβ 1-40 -induced changes in mood-related behaviors and biochemical parameters in ex vivo hippocampal slices from mice. Atorvastatin treatment (10 mg/kg, p.o., once a day for seven consecutive days) abolished depressive-like and anhedonic-like behaviors induced by Aβ 1-40 (400 pmol/site, icv) infusion. Aβ 1-40 -induced hippocampal cell damage was reversed by atorvastatin treatment. Aβ 1-40 infusion decreased glutamate uptake in hippocampal slices, and atorvastatin did not altered it. Glutamine synthetase activity was not altered by any treatment. Atorvastatin also increased hippocampal mature brain-derived neurotrophic factor (mBDNF)/precursor BDNF (proBDNF) ratio, suggesting an increase of proBDNF to mBDNF cleavage. Accordingly, increased tissue-type plasminogen activator (tPA) and p11 genic expression were observed in hippocampus of atorvastatin-treated mice. Atorvastatin displays antidepressant-like and neuroprotective effects against Aβ 1-40 -induced toxicity, and these effects may involve tPA- and p11-mediated cleavage of proBDNF to mBDNF.

  12. Rescue of axotomized rubrospinal neurons by brain-derived neurotrophic factor (BDNF) in the developing opossum, Didelphis virginiana.

    Science.gov (United States)

    Wang, X M; Terman, J R; Martin, G F

    1999-12-10

    Many rubrospinal neurons die in developing opossums when their axon is cut at thoracic levels of the spinal cord and in the present study we asked whether they can be rescued by brain-derived neurotrophic factor (BDNF). Bilateral injections of Fast Blue (FB) were made into the rostral lumbar cord to prelabel rubrospinal neurons and 5 days later the rubrospinal tract was cut unilaterally by hemisecting the thoracic cord. Immediately after hemisection, BDNF-soaked gelfoam was placed into the lesion cavity. Since pilot data indicated that one application of BDNF was not sufficient to produce a rescue effect, a second application was made 7 days later. Seven days after the second application the pups were killed by an overdose of anesthetic so that the red nucleus contralateral and ipsilateral to the lesion site could be examined for labeled neurons. The rubrospinal tract is almost entirely crossed, so the red nucleus contralateral to the lesion contained many axotomized neurons, whereas the red nucleus ipsilateral to it did not. Age-matched controls were subjected to the same procedures, but the gelfoam applied to the lesion site in the experimental animals was soaked only in the vehicle used to deliver BDNF. In all cases, labeled neurons were fewer in number in the red nucleus contralateral to the lesion than ipsilateral to it. It was of particular interest, however, that labeled neurons contralateral to the lesion were more numerous in the animals treated with BDNF than in the controls. We conclude that BDNF rescues at least some rubrospinal neurons from axotomy-induced cell death in developing opossums suggesting that loss of access to BDNF, and perhaps other neurotrophins, contributes to failure of rubrospinal neurons to survive axotomy.

  13. Inhibition of Inwardly Rectifying Potassium (Kir 4.1 Channels Facilitates Brain-Derived Neurotrophic Factor (BDNF Expression in Astrocytes

    Directory of Open Access Journals (Sweden)

    Masato Kinboshi

    2017-12-01

    Full Text Available Inwardly rectifying potassium (Kir 4.1 channels in astrocytes regulate neuronal excitability by mediating spatial potassium buffering. Although dysfunction of astrocytic Kir4.1 channels is implicated in the development of epileptic seizures, the functional mechanisms of Kir4.1 channels in modulating epileptogenesis remain unknown. We herein evaluated the effects of Kir4.1 inhibition (blockade and knockdown on expression of brain-derived neurotrophic factor (BDNF, a key modulator of epileptogenesis, in the primary cultures of mouse astrocytes. For blockade of Kir4.1 channels, we tested several antidepressant agents which reportedly bound to and blocked Kir4.1 channels in a subunit-specific manner. Treatment of astrocytes with fluoxetine enhanced BDNF mRNA expression in a concentration-dependent manner and increased the BDNF protein level. Other antidepressants (e.g., sertraline and imipramine also increased the expression of BDNF mRNA with relative potencies similar to those for inhibition of Kir4.1 channels. In addition, suppression of Kir4.1 expression by the transfection of small interfering RNA (siRNA targeting Kir4.1 significantly increased the mRNA and protein levels of BDNF. The BDNF induction by Kir4.1 siRNA transfection was suppressed by the MEK1/2 inhibitor U0126, but not by the p38 MAPK inhibitor SB202190 or the JNK inhibitor SP600125. The present results demonstrated that inhibition of Kir4.1 channels facilitates BDNF expression in astrocytes primarily by activating the Ras/Raf/MEK/ERK pathway, which may be linked to the development of epilepsy and other neuropsychiatric disorders.

  14. Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder: a correlation with BDNF expression.

    Directory of Open Access Journals (Sweden)

    Anilkumar Pillai

    Full Text Available BACKGROUND: Current theories on the pathophysiology of schizophrenia suggest altered brain plasticity such as decreased neural proliferation and migration, delayed myelination, and abnormal synaptic modeling, in the brain of subjects with schizophrenia. Though functional alterations in BDNF, which plays important role in neuroplasticity, are implicated in many abnormalities found in schizophrenia, the regulatory mechanism(s involved in the abnormal signaling of BDNF in schizophrenia is not clear. The present study investigated whether Sprouty2, a regulator of growth factor signaling, is abnormally expressed in schizophrenia, and is associated with the changes in BDNF mRNA in this disorder. The potential effect of antipsychotic drugs on Sprouty2 expression was tested in adult rats. METHODS AND FINDINGS: Sprouty2 and BDNF gene expression were analyzed in dorsolateral prefrontal cortex samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA in 100 individuals (35 with schizophrenia, 31 with bipolar disorder, and 34 psychiatrically normal controls showed significantly decreased expression of Sprouty2 and BDNF in both schizophrenia and bipolar disorder. Moreover, a significant correlation between these two genes existed in control, schizophrenia and bipolar subjects. Long-term treatment with antipsychotic drugs, haloperidol and olanzapine, showed differential effects on both Sprouty2 and BDNF mRNA and protein levels in the frontal cortex of rats. CONCLUSION: These findings demonstrating decreased expression of Sprouty2 associated with changes in BDNF, suggest the possibility that these decreases are secondary to treatment rather than to factors that are significant in the disease process of either schizophrenia and/or bipolar disorder. Further exploration of Sprouty2-related signal transduction pathways may be helpful to design novel treatment strategies for these disorders.

  15. 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

  16. Correlation of point defects in CdZnTe with charge transport:application to room-temperature X-ray and gamma-ray detectors. Final Technical Report

    International Nuclear Information System (INIS)

    Giles, Nancy C.

    2003-01-01

    The primary goal of this project has been to characterize and identify point defects (e.g., impurities, vacancies, vacancy-impurity complexes, etc.) in CdZnTe and determine the mechanisms by which these defects influence the carrier μτproducts. Special attention is given to the role of shallow donors, shallow acceptors, and deeper acceptors. There are two experimental focus areas in the project: (1) liquid-helium photoluminescence (PL) and PL excitation spectroscopy are used to identify and characterize donors and acceptors and to determine zinc molar fraction; and (2) electron paramagnetic resonance (EPR) and photoinduced EPR experiments are performed at liquid-helium temperature to identify paramagnetic point defects and to determine the concentration of these defects. Results from the two experimental focus areas are correlated with detector performance parameters (e.g., electron and hole μτ products), crystal growth conditions, and microstructure analyses

  17. 76 FR 51120 - Denial of Motor Vehicle Defect Petition

    Science.gov (United States)

    2011-08-17

    ... tests. FMVSS 208 All new passenger cars and lights trucks must comply with Federal Motor Vehicle Safety... Vehicle Defect Petition AGENCY: National Highway Traffic Safety Administration (NHTSA), Department of Transportation. ACTION: Denial of motor vehicle defect petition. SUMMARY: This document denies a March 2, 2010...

  18. 49 CFR 215.115 - Defective roller bearing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defective roller bearing. 215.115 Section 215.115... § 215.115 Defective roller bearing. (a) A railroad may not place or continue in service a car, if the car has— (1) A roller bearing that shows signs of having been overheated as evidenced by— (i...

  19. 49 CFR 215.111 - Defective plain bearing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defective plain bearing. 215.111 Section 215.111... § 215.111 Defective plain bearing. A railroad may not place or continue in service a car, if the car has a plain bearing— (a) That is missing, cracked, or broken; (b) On which the bearing liner— (1) Is...

  20. 49 CFR 215.117 - Defective roller bearing adapter.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defective roller bearing adapter. 215.117 Section... Suspension System § 215.117 Defective roller bearing adapter. A railroad may not place or continue in service a car, if the car has a roller bearing adapter that is— (a) Cracked or broken; (b) Not in its design...

  1. 49 CFR 215.113 - Defective plain bearing wedge.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defective plain bearing wedge. 215.113 Section 215... Suspension System § 215.113 Defective plain bearing wedge. A railroad may not place or continue in service a car, if a plain bearing wedge on that car is— (a) Missing; (b) Cracked; (c) Broken; or (d) Not located...

  2. Congenital disorders of glycosylation: new defects and still counting

    NARCIS (Netherlands)

    Scott, K.; Gadomski, T.; Kozicz, L.T.; Morava, E.

    2014-01-01

    Almost 50 inborn errors of metabolism have been described due to congenital defects in N-linked glycosylation. These phenotypically diverse disorders typically present as clinical syndromes, affecting multiple systems including the central nervous system, muscle function, transport, regulation,

  3. Necessity and effects of dynamic systems for railway wheel defect detection

    Directory of Open Access Journals (Sweden)

    S. Vesković

    2012-07-01

    Full Text Available State of railway vehicles highly influences transport safety due to vehicle derailments and in the same time worsens the quality of freight and passenger transportation. One of important elements that influence the state of railway vehicles is the wheel state. Wheel defects are common in railway transport. Therefore, timely defect detection is very important. This paper presents ways and effects of timely detection of wheel defects.

  4. Interaction of BDNF rs6265 variants and energy and protein intake in the risk for glucose intolerance and type 2 diabetes in middle-aged adults.

    Science.gov (United States)

    Daily, James W; Park, Sunmin

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) is associated with the risk for Alzheimer's disease and type 2 diabetes. The aim of this study was to examine the association of BDNF variants with type 2 diabetes and the interactions of different BDNF genotypes with dietary habits and food and nutrient intakes in middle-aged adults. The study population included 8840 adults ages 40 to 65 y from the Ansan and Asung areas in the Korean Genome Epidemiology Study, a cross-sectional study of Korean adults, conducted from 2001 to 2002. Adjusted odd ratios for the prevalence of glucose intolerance and type 2 diabetes according to BDNF genotypes were calculated after adjusting for age, sex, residence area, body mass index, physical activity, and smoking and stress status. Nutrient intake was calculated from usual food intake determined by semiquantitative food frequencies using the nutrient assessment software. BDNF rs6265 Val/Met and Met/Met variants were negatively associated with the risk for type 2 diabetes after adjusting for covariates. Serum glucose levels after glucose loading and hemoglobin A1c, but not serum insulin levels, also were negatively associated with BDNF Val/Met and Met/Met. In subgroup analysis, sex and stress levels had an interaction with BDNF Val/Met in the risk for type 2 diabetes. Glucose-intolerant and diabetic, but not nondiabetic, patients with BDNF Met/Met had nominally, but significantly higher intakes of energy than those with BDNF Val/Val. BDNF rs6265 had consistent gene-diet interactions with energy and protein intake. With low-energy, low-protein, and high-carbohydrate intake, BDNF Val/Met lowered the risk for type 2 diabetes after adjusting for confounding factors. BDNF Val/Met did not compensate for developing type 2 diabetes with high-energy intake. Additionally, indexes of insulin resistance and insulin secretion showed the same gene-energy interaction as type 2 diabetes. BDNF Val/Met and Met/Met variants (rs6265) decreases the risk for

  5. Defects in hardwood timber

    Science.gov (United States)

    Roswell D. Carpenter; David L. Sonderman; Everette D. Rast; Martin J. Jones

    1989-01-01

    Includes detailed information on all common defects that may aRect hardwood trees and logs. Relationships between manufactured products and those forms of round material to be processed from the tree for conversion into marketable products are discussed. This handbook supersedes Agriculture Handbook No. 244, Grade defects in hardwood timber and logs, by C.R. Lockard, J...

  6. Craniotomy Frontal Bone Defect

    African Journals Online (AJOL)

    2018-03-01

    Mar 1, 2018 ... with cosmetic deformity of fore head (Figure 1), and he claimed that he could not get job because of ... 1: Pre-operative forontal view of patient. Figure 2: Intra operative photography of defect (A) reconstructed defect (B) ... with a cosmetic deformity of forehead on left side. (4nA and B). He was a candidate for.

  7. Could BDNF be involved in compensatory mechanisms to maintain cognitive performance despite acute sleep deprivation? An exploratory study.

    Science.gov (United States)

    Giacobbo, Bruno Lima; Corrêa, Márcio Silveira; Vedovelli, Kelem; de Souza, Carlos Eduardo Bruhn; Spitza, Letícia Martins; Gonçalves, Lucas; Paludo, Nathália; Molina, Rachel Dias; da Rosa, Eduarda Dias; Argimon, Irani Iracema de Lima; Bromberg, Elke

    2016-01-01

    Neuroimaging studies suggest that acute sleep deprivation can lead to adaptations, such as compensatory recruitment of cerebral structures, to maintain cognitive performance despite sleep loss. However, the understanding of the neurochemical alterations related to these adaptations remains incomplete. Investigate BDNF levels, cognitive performance and their relations in healthy subjects after acute sleep deprivation. Nineteen sleep deprived (22.11±3.21years) and twenty control (25.10±4.42years) subjects completed depression, anxiety and sleep quality questionnaires. Sleep deprived group spent a full night awake performing different playful activities to keep themselves from sleeping. Attention, response inhibition capacity and working memory (prefrontal cortex-dependent) were assessed with Stroop and Digit Span tests. Declarative memory (hippocampus-dependent) was assessed with Logical Memory test. Serum BDNF was measured by sandwich ELISA. Data were analyzed with independent samples T-test, ANOVA, ANCOVA and curve estimation regressions. psleep deprived group showed higher BDNF levels and normal performance on attention, response inhibition capacity and working memory. However, declarative memory was impaired. A sigmoidal relation between BDNF and Stroop Test scores was found. Increased BDNF could be related, at least in part, to the maintenance of normal prefrontal cognitive functions after sleep deprivation. This potential relation should be further investigated. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Ketamine alters behavior and decreases BDNF levels in the rat brain as a function of time after drug administration

    Directory of Open Access Journals (Sweden)

    Daiane B. Fraga

    2013-09-01

    Full Text Available Objective: To evaluate behavioral changes and brain-derived neurotrophic factor (BDNF levels in rats subjected to ketamine administration (25 mg/kg for 7 days. Method: Behavioral evaluation was undertaken at 1 and 6 hours after the last injection. Results: We observed hyperlocomotion 1 hour after the last injection and a decrease in locomotion after 6 hours. Immobility time was decreased and climbing time was increased 6 hours after the last injection. BDNF levels were decreased in the prefrontal cortex and amygdala when rats were killed 6 hours after the last injection, compared to the saline group and to rats killed 1 hour after the last injection. BDNF levels in the striatum were decreased in rats killed 6 hours after the last ketamine injection, and BDNF levels in the hippocampus were decreased in the groups that were killed 1 and 6 hours after the last injection. Conclusion: These results suggest that the effects of ketamine on behavior and BDNF levels are related to the time at which they were evaluated after administration of the drug.

  9. Sex Differences in the Impact of BDNF Genotype on the Longitudinal Relationship between Physical Activity and Cognitive Performance.

    Science.gov (United States)

    Watts, Amber; Andrews, Shea J; Anstey, Kaarin J

    2018-02-02

    Physical activity may preserve cognitive function in older adults, but benefits vary by sex and genetic factors. We tested the longitudinal association between physical activity and cognitive performance to de termine whether a common genetic polymorphism for brain-derived neurotrophic factor (BDNF Val66Met) moderated this effect. In a 12-year longitudinal population-based sample of older adults (n = 2,218), we used growth curve modeling to investigate whether the benefits of physical activity on cognitive preservation differed by BDNF genotype and sex across multiple cognitive domains including processing speed, attention, working memory, and episodic verbal memory. The relationship between physical activity and cognitive performance was dependent on BDNF carrier status in males (Δχ2 [Δdf] = 12.94 [4], p = 0.01), but not in females (Δχ2 [Δdf] = 4.38 [4], p = 0.36). Cognition benefited from physical activity in male BDNF met noncarriers, but not met carriers, whereas cognition was not statistically significantly related to physical activity in females regardless of genotype. We observed longitudinal, but not cross-sectional, effects of physical activity on cognitive performance. Our study highlights the importance of longitudinal follow-up and consideration of sex differences in the relationships between physical activity, BDNF genotype, and cognitive decline. The findings contribute to understanding gene-lifestyle interactions in promoting cognitive health. © 2018 S. Karger AG, Basel.

  10. The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Adam Dinoff

    Full Text Available The mechanisms through which physical activity supports healthy brain function remain to be elucidated. One hypothesis suggests that increased brain-derived neurotrophic factor (BDNF mediates some cognitive and mood benefits. This meta-analysis sought to determine the effect of exercise training on resting concentrations of BDNF in peripheral blood.MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after exercise interventions ≥ 2 weeks. Risk of bias was assessed using standardized criteria. Standardized mean differences (SMDs were generated from random effects models. Risk of publication bias was assessed using funnel plots and Egger's test. Potential sources of heterogeneity were explored in subgroup analyses.In 29 studies that met inclusion criteria, resting concentrations of peripheral blood BDNF were higher after intervention (SMD = 0.39, 95% CI: 0.17-0.60, p < 0.001. Subgroup analyses suggested a significant effect in aerobic (SMD = 0.66, 95% CI: 0.33-0.99, p < 0.001 but not resistance training (SMD = 0.07, 95% CI: -0.15-0.30, p = 0.52 interventions. No significant difference in effect was observed between males and females, nor in serum vs plasma.Aerobic but not resistance training interventions increased resting BDNF concentrations in peripheral blood.

  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.

  12. The Met-genotype of the BDNF Val66Met polymorphism is associated with reduced Stroop interference in elderly.

    Science.gov (United States)

    Gajewski, Patrick D; Hengstler, Jan G; Golka, Klaus; Falkenstein, Michael; Beste, Christian

    2012-12-01

    Aging is accompanied by impairments of executive functions that rely on the functional integrity of fronto-striatal networks. This integrity is modulated by the release of neurotrophins like the brain-derived-neurotrophic factor (BDNF). Here, we investigate effects of the functional BDNF Val66Met polymorphism on interference processing in 131 healthy elderly subjects using event-related potentials (ERPs). In a Stroop task, participants had to indicate the name or the colour of colour-words while colour was either compatible or incompatible with the name. We show that susceptibility to Stroop-interference is affected by the BDNF Val66Met polymorphism: the Met-allele carriers showed better performance and enhanced N450 in interference trials. Other processes necessary to prepare and allocate cognitive resources to a particular task were not affected by BDNF Val66Met polymorphism, underlining the specificity of the observed effects. The observed performance and ERP difference is possibly due to dopamine related effects of BDNF in fronto-striatal networks, where it putatively mediates a shift in the balance of the direct and indirect pathway involved in inhibitory functions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. 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...

  14. Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional BDNF knock-out mice

    OpenAIRE

    Klein, AB; Santini, MA; Aznar, S; Knudsen, GM; Rios, M

    2010-01-01

    Changes in brain-derived neurotrophic factor (BDNF) expression have been implicated in the etiology of psychiatric disorders. To investigate pathological mechanisms elicited by perturbed BDNF signaling, we examined mutant mice with central depletion of BDNF (BDNF2L/2LCk-cre). A severe impairment specific for the serotonin 2A receptor (5-HT2A) in prefrontal cortex was described previously in these mice. This is of much interest, as 5-HT2A receptors have been linked to neuropsychiatric disorder...

  15. 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…

  16. 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...

  17. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

    DEFF Research Database (Denmark)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders

    2010-01-01

    mRNA expression in both the dentate gyrus of the dorsal hippocampus and the CA3 region of the ventral hippocampus indicating that there is no simple link between depression-like behaviors per se and brain BDNF levels in rats. However, a significant increase in BDNF mRNA levels in the dentate gyrus...

  18. Inherited behaviors, BDNF expression and response to treatment in a novel multifactorial rat model for depression.

    Science.gov (United States)

    Gersner, Roman; Gal, Ram; Levit, Ofir; Moshe, Hagar; Zangen, Abraham

    2014-06-01

    Major depressive disorder (MDD) is a common and devastating mental illness behaviorally characterized by various symptoms, including reduced motivation, anhedonia and psychomotor retardation. Although the etiology of MDD is still obscure, a genetic predisposition appears to play an important role. Here we used, for the first time, a multifactorial selective breeding procedure to generate a distinct 'depressed' rat line (DRL); our selection was based upon mobility in the forced swim test, sucrose preference and home-cage locomotion, three widely used tests associated with core characteristics of MDD. Other behavioral effects of the selection process, as well as changes in brain-derived neurotrophic factor (BDNF) and the response to three antidepressant treatments, were also examined. We show that decreased mobility in the forced swim test and decreased sucrose preference (two directly selected traits), as well as decreased exploration in the open field test (an indirectly selected trait), are hereditary components in DRL rats. In addition, lower BDNF levels are observed in the dorsal hippocampus of DRL rats, complying with the neurotrophic hypothesis of depression. Finally, electroconvulsive shocks (ECS) but not pharmacological treatment normalizes both the depressive-like behavioral impairments and the BDNF-related molecular alterations in DRL rats, highlighting the need for robust treatment when the disease is inherited and not necessarily triggered by salient chronic stress. We therefore provide a novel multifactorial genetic rat model for depression-related behaviors. The model can be used to further study the etiology of the disease and suggest molecular correlates and possible treatments for the disease.

  19. Predicting the use of corporal punishment: Child aggression, parent religiosity, and the BDNF gene.

    Science.gov (United States)

    Avinun, Reut; Davidov, Maayan; Mankuta, David; Knafo-Noam, Ariel

    2018-03-01

    Corporal punishment (CP) has been associated with deleterious child outcomes, highlighting the importance of understanding its underpinnings. Although several factors have been linked with parents' CP use, genetic influences on CP have rarely been studied, and an integrative view examining the interplay between different predictors of CP is missing. We focused on the separate and joint effects of religiosity, child aggression, parent's gender, and a valine (Val) to methionine (Met) substitution in the brain-derived neurotrophic factor (BDNF) gene. Data came from a twin sample (51% male, aged 6.5 years). We used mothers' and fathers' self-reports of CP and religiosity, and the other parent's report on child aggression. Complete data were available for 244 mothers and their 466 children, and for 217 fathers and their 409 children. The random split method was employed to examine replicability. For mothers, only the effect of religiosity appeared to replicate. For fathers, several effects predicting CP use replicated in both samples: child aggression, child sex, religiosity, and a three-way (GxExE) interaction implicating fathers' BDNF genotype, child aggression and religiosity. Religious fathers who carried the Met allele and had an aggressive child used CP more frequently; in contrast, secular fathers' CP use was not affected by their BDNF genotype or child aggression. Results were also repeated longitudinally in a subsample with age 8-9 data. Findings highlight the utility of a bio-ecological approach for studying CP use by shedding light on pertinent gene-environment interaction processes. Possible implications for intervention and public policy are discussed. © 2017 Wiley Periodicals, Inc.

  20. Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

    Science.gov (United States)

    Galinato, Melissa H.; Orio, Laura; Mandyam, Chitra D.

    2014-01-01

    Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1 h/day) or extended access (6 h/day) paradigm for 17 days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of NMDA receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct allostatic changes in

  1. Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks

    DEFF Research Database (Denmark)

    Dodds, Chris M; Henson, Richard N; Suckling, John

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation...... of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe....... In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results...

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

    OpenAIRE

    Pinheiro, Vera Lúcia Margarido

    2010-01-01

    Dissertação de mestrado em Biologia Celular e Molecular apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra 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-sinápti...

  3. Visual Experience Facilitates BDNF-Dependent Adaptive Recruitment of New Neurons in the Postembryonic Optic Tectum.

    Science.gov (United States)

    Hall, Zachary J; Tropepe, Vincent

    2018-02-21

    Postembryonic brain development is sensitive to environmental input and sensory experience, but the mechanisms underlying healthy adaptive brain growth are poorly understood. Here, we tested the importance of visual experience on larval zebrafish ( Danio rerio ) postembryonic development of the optic tectum (OT), a midbrain structure involved in visually guided behavior. We first characterized postembryonic neurogenic growth in OT, in which new neurons are generated along the caudal tectal surface and contribute appositionally to anatomical growth. Restricting visual experience during development by rearing larvae in dim light impaired OT anatomical and neurogenic growth, specifically by reducing the survival of new neurons in the medial periventricular gray zone. Neuronal survival in the OT was reduced only when visual experience was restricted for the first 5 d following new neuron generation, suggesting that tectal neurons exhibit an early sensitive period in which visual experience protects these cells from subsequent neuronal loss. The effect of dim rearing on neuronal survival was mimicked by treatment with an NMDA receptor antagonist early, but not later, in a new neuron's life. Both dim rearing and antagonist treatment reduced BDNF production in the OT, and supplementing larvae with exogenous BDNF during dim rearing prevented neuronal loss, suggesting that visual experience protects new tectal neurons through neural activity-dependent BDNF expression. Collectively, we present evidence for a sensitive period of neurogenic adaptive growth in the larval zebrafish OT that relies on visual experience-dependent mechanisms. SIGNIFICANCE STATEMENT Early brain development is shaped by environmental factors via sensory input; however, this form of experience-dependent neuroplasticity is traditionally studied as structural and functional changes within preexisting neurons. Here, we found that restricting visual experience affects development of the larval zebrafish

  4. Decreased plasma concentrations of BDNF and IGF-1 in abstinent patients with alcohol use disorders.

    Directory of Open Access Journals (Sweden)

    Nuria García-Marchena

    Full Text Available The identification of growth factors as potential biomarkers in alcohol addiction may help to understand underlying mechanisms associated with the pathogenesis of alcohol use disorders (AUDs. Previous studies have linked growth factors to neural plasticity in neurocognitive impairment and mental disorders. In order to further clarify the impact of chronic alcohol consumption on circulating growth factors, a cross-sectional study was performed in abstinent AUD patients (alcohol group, N = 91 and healthy control subjects (control group, N = 55 to examine plasma concentrations of brain-derived neurotrophic factor (BDNF, insulin-like growth factor-1 (IGF-1 and IGF-1 binding protein-3 (IGFBP-3. The association of these plasma peptides with relevant AUD-related variables and psychiatric comorbidity was explored. The alcohol group was diagnosed with severe AUD and showed an average of 13 years of problematic use and 10 months of abstinence at the moment of participating in the study. Regarding common medical conditions associated with AUD, we observed an elevated incidence of alcohol-induced liver and pancreas diseases (18.7% and psychiatric comorbidity (76.9%. Thus, AUD patients displayed a high prevalence of dual diagnosis (39.3% [mainly depression (19.9%] and comorbid substance use disorders (40.7%. Plasma BDNF and IGF-1 concentrations were significantly lower in the alcohol group than in the control group (p<0.001. Remarkably, there was a negative association between IGF-1 concentrations and age in the control group (r = -0.52, p<0.001 that was not found in the alcohol group. Concerning AUD-related variables, AUD patients with liver and pancreas diseases showed even lower concentrations of BDNF (p<0.05. In contrast, the changes in plasma concentrations of these peptides were not associated with abstinence, problematic use, AUD severity or lifetime psychiatric comorbidity. These results suggest that further research is necessary to elucidate the

  5. The BDNF Val66Met polymorphism moderates the relationship between Posttraumatic Stress Disorder and fear extinction learning.

    Science.gov (United States)

    Felmingham, Kim L; Zuj, Daniel V; Hsu, Ken Chia Ming; Nicholson, Emma; Palmer, Matthew A; Stuart, Kimberley; Vickers, James C; Malhi, Gin S; Bryant, Richard A

    2018-05-01

    The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val-Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val-Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val-Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Screening Tests for Birth Defects

    Science.gov (United States)

    ... Advocacy For Patients About ACOG Screening Tests for Birth Defects Home For Patients Search FAQs Screening Tests ... FAQ165, April 2014 PDF Format Screening Tests for Birth Defects Pregnancy What is a birth defect? What ...

  7. Melatonin Promotes Brain-Derived Neurotrophic Factor (BDNF) Expression and Anti-Apoptotic Effects in Neonatal Hemolytic Hyperbilirubinemia via a Phospholipase (PLC)-Mediated Mechanism.

    Science.gov (United States)

    Luo, Yong; Peng, Mei; Wei, Hong

    2017-12-16

    BACKGROUND Melatonin therapy shows positive effects on neuroprotective factor brain-derived neurotrophic factor (BDNF) expression and neuronal apoptosis in neonatal hemolytic hyperbilirubinemia. We hypothesized that melatonin promotes BDNF expression and anti-apoptotic effects in neonatal hemolytic hyperbilirubinemia through a phospholipase (PLC)-mediated mechanism. MATERIAL AND METHODS A phenylhydrazine hydrochloride (PHZ)-induced neonatal hemolytic hyperbilirubinemia model was constructed in neonatal rats. Four experimental groups - a control group (n=30), a PHZ group (n=30), a PHZ + melatonin group (n=30), and a PHZ + melatonin+U73122 (a PLC inhibitor) group (n=30) - were constructed. Trunk blood was assayed for serum hemoglobin, hematocrit, total and direct bilirubin, BDNF, S100B, and tau protein levels. Brain tissue levels of neuronal apoptosis, BDNF expression, PLC activity, IP3 content, phospho- and total Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV) expression, and phospho- and total cAMP response element binding protein (CREB) expression were also assayed. RESULTS PHZ-induced hemolytic hyperbilirubinemia was validated by significantly decreased serum hemoglobin and hematocrit as well as significantly increased total and direct serum bilirubin (p<0.05). Neonatal bilirubin-induced neurotoxicity was validated by significantly decreased serum BDNF, brain BDNF, and serum S100B, along with significantly increased serum tau protein (p<0.05). PHZ-induced hemolytic hyperbilirubinemia significantly decreased serum BDNF, brain BDNF, and PLC/IP3/Ca2+ pathway activation while increasing neuronal apoptosis levels (p<0.05), all of which were partially rescued by melatonin therapy (p<0.05). Pre-treatment with the PLC inhibitor U73122 largely abolished the positive effects of melatonin on PLC/IP3/Ca2+ pathway activation, downstream BDNF levels, and neuronal apoptosis (p<0.05). CONCLUSIONS Promotion of BDNF expression and anti-apoptotic effects in neonatal

  8. Single Ventricle Defects

    Science.gov (United States)

    ... heart defects along with pulmonary atresia. (Children with tetralogy of Fallot who also have pulmonary atresia may have treatment similar to others with tetralogy of Fallot.) How does it affect the heart? An opening ...

  9. Repairing Nanoparticle Surface Defects

    NARCIS (Netherlands)

    Marino, Emanuele; Kodger, Thomas E.; Crisp, R.W.; Timmerman, Dolf; MacArthur, Katherine E.; Heggen, Marc; Schall, Peter

    2017-01-01

    Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, replacing the native, insulating ligands with conductive metal chalcogenide complexes introduces structural defects within the crystalline nanostructure that act as traps for charge carriers. We

  10. 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.

  11. 49 CFR 230.100 - Defects in tender truck axles and journals.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defects in tender truck axles and journals. 230... Steam Locomotives and Tenders Running Gear § 230.100 Defects in tender truck axles and journals. (a... wheel seats that is more than 1/8 of an inch in depth. (b) Tender truck journal condemning defects...

  12. Charge mobility modification of semiconducting carbon nanotubes by intrinsic defects

    International Nuclear Information System (INIS)

    Bai, Hongcun; Ma, Yujia; Ma, Jinsuo; Mei, Jingnan; Tong, Yan; Ji, Yongqiang

    2017-01-01

    Charge carrier mobility is a central transport property in nanoscale electronics. Carbon nanotubes (CNTs) are supposed to have high carrier mobility. The preparation methods of CNTs have been greatly improved, but the defects always exist. This work presented first-principle investigations on the charge carrier mobility of carbon nanotubes containing several intrinsic defects. The charge carrier mobilities of zigzag (10, 0) tubes with Stone–Wales, mono vacant and 5/8/5 defects were studied as an example to explore the role of defects. Most carrier mobilities were decreased, but several values of mobility are unexpectedly increased upon the appearance of the defects. This interesting result is discussed based on the changes of the stretching modulus, the effective mass of the carrier and deformation potential constant induced by the defects. (paper)

  13. Gradually Increased Training Intensity Benefits Rehabilitation Outcome after Stroke by BDNF Upregulation and Stress Suppression

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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.

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

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    Harish Babu

    2009-09-01

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

  17. Electronic structure of point defects in semiconductors

    International Nuclear Information System (INIS)

    Bruneval, Fabien

    2014-01-01

    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

  18. Implications of permeation through intrinsic defects in graphene on the design of defect-tolerant membranes for gas separation.

    Science.gov (United States)

    Boutilier, Michael S H; Sun, Chengzhen; O'Hern, Sean C; Au, Harold; Hadjiconstantinou, Nicolas G; Karnik, Rohit

    2014-01-28

    Gas transport through intrinsic defects and tears is a critical yet poorly understood phenomenon in graphene membranes for gas separation. We report that independent stacking of graphene layers on a porous support exponentially decreases flow through defects. On the basis of experimental results, we develop a gas transport model that elucidates the separate contributions of tears and intrinsic defects on gas leakage through these membranes. The model shows that the pore size of the porous support and its permeance critically affect the separation behavior, and reveals the parameter space where gas separation can be achieved regardless of the presence of nonselective defects, even for single-layer membranes. The results provide a framework for understanding gas transport in graphene membranes and guide the design of practical, selectively permeable graphene membranes for gas separation.

  19. Xiaochaihutang attenuates depressive/anxiety-like behaviors of social isolation-reared mice by regulating monoaminergic system, neurogenesis and BDNF expression.

    Science.gov (United States)

    Ma, Jie; Wang, Fang; Yang, Jingyu; Dong, Yingxu; Su, Guangyue; Zhang, Kuo; Pan, Xing; Ma, Ping; Zhou, Tingshuo; Wu, Chunfu

    2017-08-17

    Xiaochaihutang (XCHT), as a classical herbal formula for the treatment of "Shaoyang syndrome" has been demonstrated to exert an antidepressant effect in multiple animal models of depression as shown in our previous studies. However, the effects of XCHT on social isolation (SI)-reared mice have not been investigated. This study aims to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice, and its implicated mechanisms, including alterations in the monoaminergic system, neurogenesis and neurotrophin expression. Male C57 BL/6J mice (aged 4 weeks after weaning) were reared isolatedly for 8 weeks and XCHT (0.8, 2.3, 7.0g/kg) were given by gavage once a day. Forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated-plus maze test (EPM) and intruder-induced aggression test were used to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice after administration of XCHT for 6 weeks. HPLC-MS/MS was performed to quantify the levels of neurotransmitters in the hippocampus by in vivo microdialysis, while western immunoblotting was used to evaluate the action of XCHT on the synthesis, transport and degradation of monoamine neurotransmitters. Immunofluorescence was used to study the effects of XCHT on neurogenesis and neurotrophin expression, including Ki-67, DCX, BrdU and BDNF. Our results showed that administration of XCHT (0.8, 2.3 and 7.0g/kg) for 6 weeks significantly attenuated the increase in immobility time in TST and FST, improved the anxiety-like behaviors in OFT and EPM, and improved the aggressive behaviors of SI-reared mice. XCHT significantly elevated monoamine neurotransmitters levels and inhibited 5-HT turnover (5-HIAA/5-HT) in hippocampal microdialysates of SI-reared mice. In addition, we found XCHT enhanced monoamine neurotransmitter synthesis enzymes (TPH2 and TH) expressions, inhibited serotonin transporter (SERT) expression and decreased monoamine neurotransmitter

  20. Enriched Environment Attenuates Surgery-Induced Impairment of Learning, Memory, and Neurogenesis Possibly by Preserving BDNF Expression.

    Science.gov (United States)

    Fan, Dan; Li, Jun; Zheng, Bin; Hua, Lei; Zuo, Zhiyi

    2016-01-01

    Postoperative cognitive dysfunction (POCD) is a significant clinical syndrome. Neurogenesis contributes to cognition. It is known that enriched environment (EE) enhances neurogenesis. We determined whether EE attenuated surgery-induced cognitive impairment and whether growth factors and neurogenesis played a role in the EE effect. Eight-week-old C57BL/6J mice were subjected to carotid artery exposure. Their learning and memory were assessed by Barnes maze, and fear conditioning started 2 weeks after the surgery. Growth factor expression and cell genesis were determined at various times after the surgery. Surgery increased the time for the mice to identify the target hole in the Barnes maze and reduced context-related freezing behavior. Surgery also reduced the expression of brain-derived neurotrophic factor (BDNF) and neurogenesis in the hippocampus. These effects were attenuated by EE. EE also attenuated surgery-induced reduction of phosphorylated/activated tropomyosin-related kinase B (TrkB) and extracellular signal-regulated kinases (ERK), components of BDNF signaling pathway. ANA-12, a selective TrkB antagonist, blocked the effects of EE on cognition, phosphorylation of TrkB and ERK, and neurogenesis. These results provide initial evidence that surgery reduces BDNF expression and neurogenesis in the hippocampus. Our results suggest that EE reduces surgery-induced impairment of learning, memory, and neurogenesis by preserving BDNF expression.

  1. Recurrent long-lasting tethering reduces BDNF protein levels in the dorsal hippocampus and frontal cortex in pigs

    NARCIS (Netherlands)

    Vry, de J.; Prickaerts, J.; Jetten, M.; Hulst, M.M.; Steinbusch, H.W.M.; Hove, van den D.L.; Schuurman, T.; Staay, van der F.J.

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) signaling has been implicated in the onset of depression and in antidepressant efficacy, although the exact role of this neurotrophin in the pathophysiology of depression remains to be elucidated. Also, the interaction between chronic stress, which may

  2. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

    Science.gov (United States)

    Zhao, Mingzhe; Chen, Lu; Yang, Jiarun; Han, Dong; Fang, Deyu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Ma, Jingsong; Wang, Lin; Jiang, Shixiang; Song, Xuejia; Zhou, Jiawei; Zhang, Jian; Chen, Mingqi; Qi, Dong; Yang, Yanjie; Pan, Hui

    2018-02-01

    Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway.

    Science.gov (United States)

    Zhang, Lu; Fang, Yu; Xu, Yuming; Lian, Yajun; Xie, Nanchang; Wu, Tianwen; Zhang, Haifeng; Sun, Limin; Zhang, Ruifang; Wang, Zhenhua

    2015-01-01

    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.

  5. Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis.

    Science.gov (United States)

    Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Faller, Cristiano Julio; Ceretta, Renan A; Petronilho, Fabricia; Lopes-Borges, Jéssica; Valvassori, Samira S; Quevedo, João

    2015-08-01

    Pneumococcal meningitis is a serious infection of the central nervous system (CNS) with high fatality rates that causes reduced psychomotor performance, slight mental slowness, impairments in attention executive functions and learning and memory deficiencies. Previously, we demonstrated a correlation between memory impairment and decreased levels of brain-derived neurotropic factor (BDNF) in the hippocampi of rats subjected to pneumococcal meningitis. Emerging evidence demonstrates that histone acetylation regulates neurotrophins; therefore, a potential molecular intervention against cognitive impairment in bacterial meningitis may be the histone deacetylase (HDAC) inhibitor, sodium butyrate, which stimulates the acetylation of histones and increases BDNF expression. In this study, animals received either artificial cerebrospinal fluid as a placebo or a Streptococcus pneumoniae suspension at a concentration of 5 × 10(9) colony-forming units (CFU/mL). The animals received antibiotic treatment as usual and received saline or sodium butyrate as an adjuvant treatment. Ten days after, meningitis was induced; the animals were subjected to open-field habituation and the step-down inhibitory avoidance task. Immediately after these behavioural tasks, the animals were killed, and their hippocampi were removed to evaluate the expression of BDNF, nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). In the meningitis group that received saline, the animals presented memory impairment in both behavioural tasks, and hippocampal BDNF and GDNF expression was decreased. Sodium butyrate was able to prevent memory impairment and re-establish hippocampal neurotrophin expression in experimental pneumococcal meningitis.

  6. BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration

    Science.gov (United States)

    Gao, Mingyong; Lu, Paul; Lynam, Dan; Bednark, Bridget; Campana, W. Marie; Sakamoto, Jeff; Tuszynski, Mark

    2016-12-01

    Objective. We combined implantation of multi-channel templated agarose scaffolds with growth factor gene delivery to examine whether this combinatorial treatment can enhance peripheral axonal regeneration through long sciatic nerve gaps. Approach. 15 mm long scaffolds were templated into highly organized, strictly linear channels, mimicking the linear organization of natural nerves into fascicles of related function. Scaffolds were filled with syngeneic bone marrow stromal cells (MSCs) secreting the growth factor brain derived neurotrophic factor (BDNF), and lentiviral vectors expressing BDNF were injected into the sciatic nerve segment distal to the scaffold implantation site. Main results. Twelve weeks after injury, scaffolds supported highly linear regeneration of host axons across the 15 mm lesion gap. The incorporation of BDNF-secreting cells into scaffolds significantly increased axonal regeneration, and additional injection of viral vectors expressing BDNF into the distal segment of the transected nerve significantly enhanced axonal regeneration beyond the lesion. Significance. Combinatorial treatment with multichannel bioengineered scaffolds and distal growth factor delivery significantly improves peripheral nerve repair, rivaling the gold standard of autografts.

  7. 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…

  8. 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.

  9. Predicting Response Trajectories during Cognitive-Behavioural Therapy for Panic Disorder: No Association with the BDNF Gene or Childhood Maltreatment.

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    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. Differential Expression of Sox11 and Bdnf mRNA Isoforms in the Injured and Regenerating Nervous Systems

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    Felix L. Struebing

    2017-11-01

    Full Text Available In both the central nervous system (CNS and the peripheral nervous system (PNS, axonal injury induces changes in neuronal gene expression. In the PNS, a relatively well-characterized alteration in transcriptional activation is known to promote axonal regeneration. This transcriptional cascade includes the neurotrophin Bdnf and the transcription factor Sox11. Although both molecules act to facilitate successful axon regeneration in the PNS, this process does not occur in the CNS. The present study examines the differential expression of Sox11 and Bdnf mRNA isoforms in the PNS and CNS using three experimental paradigms at different time points: (i the acutely injured CNS (retina after optic nerve crush and PNS (dorsal root ganglion after sciatic nerve crush, (ii a CNS regeneration model (retina after optic nerve crush and induced regeneration; and (iii the retina during a chronic form of central neurodegeneration (the DBA/2J glaucoma model. We find an initial increase of Sox11 in both PNS and CNS after injury; however, the expression of Bdnf isoforms is higher in the PNS relative to the CNS. Sustained upregulation of Sox11 is seen in the injured retina following regeneration treatment, while the expression of two Bdnf mRNA isoforms is suppressed. Furthermore, two isoforms of Sox11 with different 3′UTR lengths are present in the retina, and the long isoform is specifically upregulated in later stages of glaucoma. These results provide insight into the molecular cascades active during axonal injury and regeneration in mammalian neurons.

  11. Involvement of the BDNF Gene in Loneliness in Adolescence : A Report of Opposite Gene Effects in Boys and Girls

    NARCIS (Netherlands)

    Verhagen, Maaike; van Roekel, Eeske; Engels, Rutger C. M. E.

    2014-01-01

    Previous research has shown that loneliness has a heritable component and that genes within the serotonin-, dopamine-, and oxytocin systems are related to loneliness in adolescence. In the present study, the relation between the BDNF Val66Met polymorphism and loneliness in adolescent boys and girls

  12. The Brain-Uterus Connection: Brain Derived Neurotrophic Factor (BDNF) and Its Receptor (Ntrk2) Are Conserved in the Mammalian Uterus

    Science.gov (United States)

    Wessels, Jocelyn M.; Wu, Liang; Leyland, Nicholas A.; Wang, Hongmei; Foster, Warren G.

    2014-01-01

    The neurotrophins are neuropeptides that are potent regulators of neurite growth and survival. Although mainly studied in the brain and nervous system, recent reports have shown that neurotrophins are expressed in multiple target tissues and cell types throughout the body. Additionally, dysregulation of neurotrophins has been linked to several disease conditions including Alzheimer's, Parkinson's, Huntington's, psychiatric disorders, and cancer. Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family that elicits its actions through the neurotrophic tyrosine receptor kinase type 2 (Ntrk2). Together BDNF and Ntrk2 are capable of activating the adhesion, angiogenesis, apoptosis, and proliferation pathways. These pathways are prominently involved in reproductive physiology, yet a cross-species examination of BDNF and Ntrk2 expression in the mammalian uterus is lacking. Herein we demonstrated the conserved nature of BDNF and Ntrk2 across several mammalian species by mRNA and protein sequence alignment, isolated BDNF and Ntrk2 transcripts in the uterus by Real-Time PCR, localized both proteins to the glandular and luminal epithelium, vascular smooth muscle, and myometrium of the uterus, determined that the major isoforms expressed in the human endometrium were pro-BDNF, and truncated Ntrk2, and finally demonstrated antibody specificity. Our findings suggest that BDNF and Ntrk2 are transcribed, translated, and conserved across mammalian species including human, mouse, rat, pig, horse, and the bat. PMID:24714156

  13. The brain-uterus connection: brain derived neurotrophic factor (BDNF) and its receptor (Ntrk2) are conserved in the mammalian uterus.

    Science.gov (United States)

    Wessels, Jocelyn M; Wu, Liang; Leyland, Nicholas A; Wang, Hongmei; Foster, Warren G

    2014-01-01

    The neurotrophins are neuropeptides that are potent regulators of neurite growth and survival. Although mainly studied in the brain and nervous system, recent reports have shown that neurotrophins are expressed in multiple target tissues and cell types throughout the body. Additionally, dysregulation of neurotrophins has been linked to several disease conditions including Alzheimer's, Parkinson's, Huntington's, psychiatric disorders, and cancer. Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family that elicits its actions through the neurotrophic tyrosine receptor kinase type 2 (Ntrk2). Together BDNF and Ntrk2 are capable of activating the adhesion, angiogenesis, apoptosis, and proliferation pathways. These pathways are prominently involved in reproductive physiology, yet a cross-species examination of BDNF and Ntrk2 expression in the mammalian uterus is lacking. Herein we demonstrated the conserved nature of BDNF and Ntrk2 across several mammalian species by mRNA and protein sequence alignment, isolated BDNF and Ntrk2 transcripts in the uterus by Real-Time PCR, localized both proteins to the glandular and luminal epithelium, vascular smooth muscle, and myometrium of the uterus, determined that the major isoforms expressed in the human endometrium were pro-BDNF, and truncated Ntrk2, and finally demonstrated antibody specificity. Our findings suggest that BDNF and Ntrk2 are transcribed, translated, and conserved across mammalian species including human, mouse, rat, pig, horse, and the bat.

  14. The Pilot Study of the Effect of Meditation to the Serum Brain-Derived Neurotrophic Factor (BDNF) of Medical Students, Srinakharinvirot University.

    Science.gov (United States)

    Turakitwanakan, Wanpen; Mekseepralard, Chantana; Busarakumtragul, Panaree

    2015-11-01

    Mindfulness meditation is a method to decrease stress and increase memory. So, mindfulness meditation should increase serum brain-derived neurotrophic factor (BDNF). To study the effect of mindfulness meditation on the serum BDNF of medical students. The study group consisted of 30 male and female second-year medical students that volunteered to participate in the study, aged 19.1 ± 0.55 year olds (range 18-20) from Srinakharinwirot University. Their blood was drawn to measure BDNF before and after a four-day mindfulness meditation programme. The comparison of serum BDNF levels before and after meditation were analysed by paired t-test. The subjects were 66.77%female and 33.33% male. The average serum BDNF level before the meditation was 17.67 ng/ml (SD 3.58). After meditation, there was a decrease in serum BDNF to 17.34 ng/ml, which was however not statistically significant (SD 4.04, p > 0.05). The levels of blood BDNF decreases slightly after practising meditation. We plan to investigate the reason in the future.

  15. PFOS Disturbs BDNF-ERK-CREB Signalling in Association with Increased MicroRNA-22 in SH-SY5Y Cells

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    Wu Li

    2015-01-01

    Full Text Available Perfluorooctane sulfonate (PFOS, a ubiquitous environmental pollutant, is neurotoxic to mammalian species. However, the underlying mechanism of its neurotoxicity was unclear. We hypothesized that PFOS suppresses BDNF expression to produce its neurotoxic effects by inhibiting the ERK-CREB pathway. SH-SY5Y human neuroblastoma cells were exposed to various concentrations of PFOS to examine the role of the BDNF-ERK-CREB signalling pathway in PFOS-induced apoptosis and cytotoxicity. Furthermore, to ascertain the mechanism by which PFOS reduces BDNF signalling, we examined the expression levels of miR-16 and miR-22, which potentially regulate BDNF mRNA translation at the posttranscriptional level. Results indicated that PFOS significantly decreased cell viability and induced apoptosis in SH-SY5Y cells. In addition, BDNF and pERK protein levels decreased after PFOS treatment; however, pCREB protein levels were significantly elevated in PFOS treated groups. TrkB protein expression increased in the 10 μM and 50 μM PFOS groups and significantly decreased in the 100 μM PFOS group. Our results demonstrated that PFOS exposure decreased miR-16 expression and increased miR-22 expression, which may represent a possible mechanism by which PFOS decreases BDNF protein levels. PFOS may inhibit BDNF-ERK-CREB signalling by increasing miR-22 levels, which may, in part, explain the mechanism of PFOS neurotoxicity.

  16. Plasma BDNF is associated with age-related white matter atrophy but not with cognitive function in older, non-demented adults.

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    Ira Driscoll

    Full Text Available Brain derived neurotrophic factor (BDNF seems to be involved in regulation of synaptic plasticity and neurogenesis. BDNF plasma and serum levels have been associated with depression, Alzheimer's disease, and other psychiatric and neurodegenerative disorders. In a community sample, drawn from the Baltimore Longitudinal Study of Aging (BLSA, we examined whether BDNF plasma concentration was associated with rates of age-related change in cognitive performance (n = 429 and regional brain volume (n = 59. Plasma BDNF levels, which were significantly higher in females (p0.05. Sex differences in the relationship between BDNF and the trajectories of regional brain volume changes were observed for the whole brain and frontal white matter volumes (p<0.05, whereby lower plasma BDNF was associated with steeper volume decline in females but not males. Together, our findings contribute to furthering the understanding of the relationships between plasma BDNF, structural brain integrity and cognition. Potential mechanisms mediating these relationships merit further investigation.

  17. The effect of intrathecal administration of glial activation inhibitors on dorsal horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve ligated rats.

    Science.gov (United States)

    Zhang, Xin; Xu, Yongming; Wang, Jing; Zhou, Quanhong; Pu, Shaofeng; Jiang, Wei; Du, Dongping

    2012-03-01

    Recent studies have suggested that activated glia in the spinal cord may play a vital role at different times during spinal nerve ligation (SNL)-induced neuropathic pain; therefore, glial activation inhibitors have been used as effective painkillers. Brain-derived neurotrophic factor (BDNF) is also known to be a powerful pain modulator, but it remains unclear how it contributes to the glial activation inhibitor-based treatment. This study revealed the following results: (1) intrathecal administration of minocycline (a microglial activation inhibitor) could prevent mechanical allodynia during the initiation of SNL-induced neuropathic pain, and its action was associated with the elimination of BDNF overexpression in the dorsal horn; (2) the spinal injection of fluorocitrate (an astrocytic activation inhibitor) but not minocycline could reverse mechanical allodynia during the maintenance phase of SNL-induced pain, and its action was also related to a decrease in BDNF overexpression in the dorsal horn; and (3) treatment with TrkB/Fc (a BDNF-sequestering protein) had a similar effect during both the early development and maintenance periods. These results led to the following conclusions: (1) elevated BDNF expression in the dorsal horn was required to develop and maintain neuropathic pain; (2) minocycline could only prevent mechanical allodynia in the early stages, possibly by inhibiting BDNF release from microglia; and (3) fluorocitrate could reverse existing mechanical allodynia, and its action was associated with the inhibition of BDNF upregulation induced by astrocytic activation.

  18. Comparison of Brain-Derived Neurotrophic Factor (BDNF and Insulin-like Growth Factor 1 (IGF-1 Responses to Different Endurance Training Intensities in Runner Men

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    M. Habibian

    2017-04-01

    Full Text Available Aims: Blood neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF and Insulin-like Growth Factor 1 (IGF-1, mediate exercise- induced health benefits in humans. The purpose of this study was to compare the response of BDNF and IGF-1 to different endurance training intensities in runner men. Materials & Methods: In this semi-experimental study with pre-test-posttest design in 2015, 10 people of male runners from Gorgan were selected through purposeful and accessible sampling. The endurance training protocol was 6 km running with moderate (70-75% of heart rate reserve or severe (80-85% of heart rate reserve intensity, which was performed within a week's interval. Fasting blood samples were collected before and immediately after both acute training sessions and serum levels of BDNF and IGF-1 were measured by ELISA and radioimmunoassay enzyme. Data were analyzed by SPSS 20 software using independent t-test and paired t-test. Findings: Both acute endurance training significantly increased serum levels of BDNF and IGF-1 in runners, but high intensity endurance exercises increased BDNF levels in comparison with moderate intensity (p0.05. Conclusion: Serum BDNF response in endurance athletes is affected by the intensity of exercise, so that the effect of high intensity endurance training on BDNF levels is greater than moderate intensity exercise, but the response of IGF-1 to acute endurance training is independent of the intensity of exercise.

  19. Diet Treatment Glucose Transporter Type 1 Deficiency (G1D)

    Science.gov (United States)

    2017-10-17

    GLUT1DS1; Epilepsy; Glut1 Deficiency Syndrome 1, Autosomal Recessive; Glucose Metabolism Disorders; Glucose Transport Defect; Glucose Transporter Type 1 Deficiency Syndrome; Glucose Transporter Protein Type 1 Deficiency Syndrome

  20. Effects of long-term exercise and low-level inhibition of GABAergic synapses on motor control and the expression of BDNF in the motor related cortex.

    Science.gov (United States)

    Inoue, Takahiro; Ninuma, Shuta; Hayashi, Masataka; Okuda, Akane; Asaka, Tadayoshi; Maejima, Hiroshi

    2018-01-01

    Objectives Brain-derived neurotrophic factor (BDNF) plays important roles in neuroplasticity in the brain. The objective of this study was to examine the effects of long-term exercise combined with low-level inhibition of GABAergic synapses on motor control and the expression of BDNF in the motor-related cortex. Methods ICR mice were divided into four groups based on the factors exercise and GABA A receptor inhibition. We administered the GABA A receptor antagonist bicuculline intraperitoneally (0.25 mg/kg). Mice exercised on a treadmill 5 days/week for 4 weeks. Following behavioral tests, BDNF expression in the motor cortex and cerebellar cortex was assayed using RT-PCR and ELISA. Results Exercise increased BDNF protein in the motor cortex and improved motor coordination in the rotarod test either in the presence or absence of bicuculline. BDNF mRNA expression in the motor cortex and muscle coordination in the wire hang test decreased after administration of bicuculline, whereas bicuculline administration increased mRNA and protein expression of BDNF in the cerebellum. Discussion The present study revealed that long-term exercise increased BDNF expression in the motor cortex and facilitated a transfer of motor learning from aerobic exercise to postural coordination. Thus, aerobic exercise is meaningful for conditioning motor learning to rehabilitate patients with central nervous system (CNS) disorders. However, long-term inhibition of GABA A receptors decreased the expression of cortical BDNF mRNA and decreased muscle coordination, despite the increase of BDNF in the cerebellum, suggesting that we have to consider the term of the inhibition of the GABAergic receptor for future clinical application to CNS patients.

  1. 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...

  2. Quantum computing with defects

    Science.gov (United States)

    Varley, Joel

    2011-03-01

    The development of a quantum computer is contingent upon the identification and design of systems for use as qubits, the basic units of quantum information. One of the most promising candidates consists of a defect in diamond known as the nitrogen-vacancy (NV-1) center, since it is an individually-addressable quantum system that can be initialized, manipulated, and measured with high fidelity at room temperature. While the success of the NV-1 stems from its nature as a localized ``deep-center'' point defect, no systematic effort has been made to identify other defects that might behave in a similar way. We provide guidelines for identifying other defect centers with similar 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 systems. To elucidate these points, we compare electronic structure calculations of the NV-1 center in diamond with those of several deep centers in 4H silicon carbide (SiC). Using hybrid functionals, we report formation energies, configuration-coordinate diagrams, and defect-level diagrams to compare and contrast the properties of these defects. We find that the NC VSi - 1 center in SiC, a structural analog of the NV-1 center in diamond, may be a suitable center with very different optical transition energies. We also discuss how the proposed criteria can be translated into guidelines to discover NV analogs in other tetrahedrally coordinated materials. This work was performed in collaboration with J. R. Weber, W. F. Koehl, B. B. Buckley, A. Janotti, C. G. Van de Walle, and D. D. Awschalom. This work was supported by ARO, AFOSR, and NSF.

  3. Ketamine and aminoguanidine differentially affect Bdnf and Mtor gene expression in the prefrontal cortex of adult male rats.

    Science.gov (United States)

    Silva Pereira, Vitor; Elfving, Betina; Joca, Sâmia R L; Wegener, Gregers

    2017-11-15

    The rapid and sustained antidepressant properties of ketamine provide evidence of the importance of the glutamatergic system in the neurobiology of depression. The antidepressant-like effects of ketamine are dependent on brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in limbic brain areas. The nitrergic system is closely related to the glutamatergic system and generates antidepressant-like effects when blocked. The aim of this study was to investigate whether the behavioural effects induced by the inhibition of nitric oxide (NO) synthesis by aminoguanidine or N-methyl-D-aspartate (NMDA) receptor blockade by ketamine would affect the gene expression of Bdnf and Mtor in the ventromedial prefrontal cortex in rats. The effects of ketamine or aminoguanidine were investigated in Sprague-Dawley (SD) rats, the Flinders Sensitive Line (FSL), a genetic rat model of depression, and their controls, the Flinders Resistant Line (FRL) rats. In the studies, the three protocols evaluated to which the animals/rats were exposed were: (1) pre-test and test sessions of forced swim test (FST), (2) pre-test session of FST alone, or (3) not exposed to the FST. Ketamine and aminoguanidine both induce antidepressant-like effects in SD and FSL rats. Quantitative real-time polymerase chain reaction analyses in SD rats demonstrated that none of the treatments can change the Bdnf or Mtor gene expression, but in FSL rats the treatment with ketamine increased only Bdnf gene expression. The data obtained strengthens the role of NMDA antagonists and NO inhibitors as potential antidepressant drugs, albeit with different effects on Bdnf gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Interaction effect between the BDNF Val66Met polymorphism and parental rearing for interpersonal sensitivity in healthy subjects.

    Science.gov (United States)

    Suzuki, Akihito; Matsumoto, Yoshihiko; Shibuya, Naoshi; Ryoichi, Sadahiro; Kamata, Mitsuhiro; Enokido, Masanori; Goto, Kaoru; Otani, Koichi

    2012-12-30

    Interpersonal sensitivity is defined as undue and excessive awareness of, and sensitivity to, the behaviour and feelings of others and is one of the vulnerable factors to depression. In a twin study, it was suggested that this personality trait was characterised by both genetic and environmental factors. In the present study, we examined the effects of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and parental rearing on interpersonal sensitivity in 725 healthy Japanese subjects. Assessment of interpersonal sensitivity was performed by the Japanese version of the Interpersonal Sensitivity Measure (IPSM). Perceived parental rearing was assessed by the Parental Bonding Instrument (PBI), which consists of the care and protection factors. The BDNF polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. There was no main effect of the BDNF genotype on the IPSM score, while the PBI factors except maternal care had significant main effect on the IPSM score. There was significant interaction effect between the BDNF genotype and maternal care of the PBI on the IPSM score. Post-hoc analysis of simple slopes showed that the negative relationship between the IPSM score and maternal care was strongest and significant in the Met/Met genotype group, intermediate in the Val/Met genotype group and weakest in the Val/Val genotype group. The present study suggests that the interaction between the BDNF Val66Met polymorphism and parental rearing, especially maternal care, influences interpersonal sensitivity in healthy subjects. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus.

    Science.gov (United States)

    Galinato, M H; Orio, L; Mandyam, C D

    2015-02-12

    Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1h/day) or extended access (6h/day) paradigm for 17days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of N-methyl-d-aspartate (NMDA) receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct

  6. Effects of hippotherapy on brain function, BDNF level, and physical fitness in children with ADHD.

    Science.gov (United States)

    Lee, Namju; Park, Sok; Kim, Jongkyu

    2015-06-01

    The purpose of this study was to examine the effects of hippotherapy on brain function and levels of blood-derived neurotrophic factor (BDNF) in children with attention deficit and/or hyperactivity disorder (ADHD). The hippotherapy group (HRG) included twenty children with ADHD and the control group (CG) included 19 children. All participants' physical fitness, fMRI brain scans, and blood BDNF levels were measured at baseline and after 32 weeks of participating in hippotherapy. After 32 weeks of participating in hippotherapy, the body fat of the HRG was significantly decreased (-1.12 ± 4.20%) and the body fat of the CG was increased (2.38 ± 6.35%) (p=0.049). There was no significant difference of physical fitness in both groups (p>0.05). Although there was a higher decrease in the activated insular area in the HRG (-1.59 ± 0.99) than in the CG (-1.14 ± 1.41), there was no significant difference between the two groups (p>0.05) Also, there was a higher increase in the activated cerebellum area in the HRG (1.97 ± 1.45) than in the CG (1.92 ± 1.81). However, there was no significant difference between the two groups (p>0.05). BDNF levels showed an increased tendency in the HRG (166.29 ± 277.52pg) compared to the CG (21.13 ± 686.33pg); otherwise, there was not any significant difference in these blood levels between the two groups (p>0.05). It can be assumed that big individual differences in the level of ADHD in the study participants might not cause any significant results, although there might be positive changes in the brain function of children with ADHD. Therefore, this study suggests that hippotherapy training would need to be modified and developed to increase the efficacy of hippotherapy in children with ADHD.

  7. Structure defects in cementite

    International Nuclear Information System (INIS)

    Schmitt, Bernard

    1971-01-01

    After a presentation of experimental techniques (elaboration principles, elaboration techniques, and investigation techniques for cementite thin layers and iron-carbon massive alloys), the author of this research thesis reports the study of cementite structure (interatomic distance, description and representation), reports the study of iron-carbon thin layers (structure, influence of silicon, defects), reports the study of perfect and imperfect dislocations and of plane defects in cementite. The author also reports hardness measurements, and discusses the relationships between cementite and other iron carbides

  8. Implications of defect clusters formed in cascades on free defect generation and microstructural development

    International Nuclear Information System (INIS)

    Wiedersich, H.

    1992-12-01

    A large fraction of the defects produced by irradiation with energetic neutrons or heavy ions originates in cascades. Not only increased recombination of vacancy and interstitial defects but also significant clustering of like defects occur. Both processes reduce the number of point defects available for long range migration. Consequences of defect clustering in cascades will be discussed in a semi-quantitative form with the aid of calculations using a very simplified model: Quasi-steady-state distributions of immobile vacancy and/or interstitial clusters develop which, in turn, can become significant sinks for mobile defects, and, therefore reduce their lifetime. Although cluster sinks will cause segregation and, potentially, precipitation of second phases due to local changes of composition, the finite lifetime of clusters will not lead to lasting, local compositional changes. A transition from highly dense interstitial and vacancy cluster distributions to the void swelling regime occurs when the thermal evaporation of vacancies from small vacancy clusters becomes significant at higher temperatures. Unequal clustering of vacancies and interstitials leads to an imbalance of their fluxes of in the matrix and, hence, to unequal contributions to atom transport by interstitials and by vacancies even in the quasi-steady state approximation

  9. BDNF VAL66MET Polymorphism Elevates the Risk of Bladder Cancer via MiRNA-146b in Micro-Vehicles

    Directory of Open Access Journals (Sweden)

    Cong Li

    2018-01-01

    Full Text Available Background/Aims: Emerging studies on brain-derived neurotrophic factor (BDNF have shown that might be novel biomarkers and therapeutic targets for cancer. We explore the role of BDNF in the tumorigenesis of bladder cancer and the underlying molecular mechanism. Methods: 368 patients with diagnosed bladder cancer and 352 healthy controls were enrolled to evaluate the association of BDNF and the miR-146b. Bioinformatics algorithm analysis and luciferase assay were performed to identify the target genes of miR-146b. Real-time PCR and western-blot were carried out to validate the relationship between miR-146b and CRK. MTT assay and FACS were used to evaluated the proliferation and apoptosis of cancer cells. MVs were isolated and transfect into the culture cells to confirm the above observation. Results: The clinical study shows that BDNF Met/Met was significantly associated with the risk of bladder cancer. In addition, comparing with Val/Val and Val/Met, Met/Met has lower miR-146b level. Luciferase assay shows that BDNF Val/Val is apparently enhanced miR-146b promoter-luciferase, but not BDNF Met/Met. Based on luciferase assay, CRK is a direct target gene of miR-146b. MiR-146b mimics significantly inhibited the expression of CRK and activation of AKT level. The expression of CRK and the activation of AKT (p-AKT were significantly inhibited by MV-BDNF Val/Val-miR-146b or MV-BDNF Val/Met-miR-146b, but not MV-BDNF Met/Met-miR-146b. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b obviously inhibited cell proliferation, which eliminated by CRK. Meanwhile, with MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not affect the proliferation. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b enhanced cell apoptosis, which could be eliminated by CRK. Meanwhile, MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not promote apoptosis. Conclusion: BDNF VAL66MET polymorphism is associated with miR-146b and its target gene CRK. MiR-146b and CRK mediated BDNF VAL66

  10. Growth factors and hormones pro-peptides: the unexpected adventures of the BDNF prodomain.

    Science.gov (United States)

    Zanin, Juan Pablo; Unsain, Nicolás; Anastasia, Agustin

    2017-05-01

    Most growth factors and hormones are synthesized as pre-pro-proteins which are processed to the biologically active mature protein. The pre- and prodomains are cleaved from the precursor protein in the secretory pathway or, in some cases, extracellularly. The canonical functions of these prodomains are to assist in folding and stabilization of the mature domain, to direct intra and extracellular localization, to facilitate storage, and to regulate bioavailability of their mature counterpart. Recently, exciting evidence has revealed that prodomains of certain growth factors, after cleaved from the precursor pro-protein, can act as independent active signaling molecules. In this review, we discuss the various classical functions of prodomains, and the biological consequences of these pro-peptides acting as ligands. We will focus our attention on the brain-derived neurotrophic factor prodomain (pBDNF), which has been recently described as a novel secreted ligand influencing neuronal morphology and physiology. © 2017 International Society for Neurochemistry.

  11. Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF

    DEFF Research Database (Denmark)

    Buttenschøn, H N; Demontis, D; Kaas, M

    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 may relate......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...

  12. 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.

  13. Defects in semiconductor nanostructures

    Indian Academy of Sciences (India)

    sizes were less than 100 Si atoms due to computational limitations. An interesting parallel is that current first principles calculations alluded to in §5 are size ham- pered for similar reasons. These 'defect molecule' calculations were probably the first studies in SN. We believe that a perusal of this 'ancient' scientific literature.

  14. Production of point defects

    International Nuclear Information System (INIS)

    Zuppiroli, L.

    1975-01-01

    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 [fr

  15. Fetal abdominal wall defects.

    Science.gov (United States)

    Prefumo, Federico; Izzi, Claudia

    2014-04-01

    The most common fetal abdominal wall defects are gastroschisis and omphalocele, both with a prevalence of about three in 10,000 births. Prenatal ultrasound has a high sensitivity for these abnormalities already at the time of the first-trimester nuchal scan. Major unrelated defects are associated with gastroschisis in about 10% of cases, whereas omphalocele is associated with chromosomal or genetic abnormalities in a much higher proportion of cases. Challenges in management of gastroschisis are related to the prevention of late intrauterine death, and the prediction and treatment of complex forms. With omphalocele, the main difficulty is the exclusion of associated conditions, not all diagnosed prenatally. An outline of the postnatal treatment of abdominal wall defects is given. Other rarer forms of abdominal wall defects are pentalogy of Cantrell, omphalocele, bladder exstrophy, imperforate anus, spina bifida complex, prune-belly syndrome, body stalk anomaly, and bladder and cloacal exstrophy; they deserve multidisciplinary counselling and management. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Defects in flexoelectric solids

    Science.gov (United States)

    Mao, Sheng; Purohit, Prashant K.

    2015-11-01

    A solid is said to be flexoelectric when it polarizes in proportion to strain gradients. Since strain gradients are large near defects, we expect the flexoelectric effect to be prominent there and decay away at distances much larger than a flexoelectric length scale. Here, we quantify this expectation by computing displacement, stress and polarization fields near defects in flexoelectric solids. For point defects we recover some well known results from strain gradient elasticity and non-local piezoelectric theories, but with different length scales in the final expressions. For edge dislocations we show that the electric potential is a maximum in the vicinity of the dislocation core. We also estimate the polarized line charge density of an edge dislocation in an isotropic flexoelectric solid which is in agreement with some measurements in ice. We perform an asymptotic analysis of the crack tip fields in flexoelectric solids and show that our results share some features from solutions in strain gradient elasticity and piezoelectricity. We also compute the energy release rate for cracks using simple crack face boundary conditions and use them in classical criteria for crack growth to make predictions. Our analysis can serve as a starting point for more sophisticated analytic and computational treatments of defects in flexoelectric solids which are gaining increasing prominence in the field of nanoscience and nanotechnology.

  17. Semiconductor Nanowires: Defects Update

    Science.gov (United States)

    Kavanagh, Karen L.

    2008-05-01

    Structural defects commonly observed in semiconducting nanowires by electron microscopy will be reviewed and their origins discussed. Their effects on electrical and optical properties will be illustrated with examples from GaSb, InAs, and ZnSe nanowires grown by MOCVD and MBE.

  18. 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.

  19. BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness: Associations with Working Memory Function.

    Science.gov (United States)

    Håkansson, Krister; Ledreux, Aurélie; Daffner, Kirk; Terjestam, Yvonne; Bergman, Patrick; Carlsson, Roger; Kivipelto, Miia; Winblad, Bengt; Granholm, Ann-Charlotte; Mohammed, Abdul Kadir H

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities. We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function. We conclude that the BDNF increase we found after physical exercise more probably has a peripheral than a central origin, but that the association between post-intervention BDNF levels and cognitive function could have implications for BDNF responsivity in serum as a potential marker of cognitive health.

  20. BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury

    Czech Academy of Sciences Publication Activity Database

    Chumak, Tetyana; Rüttiger, L.; Lee, S.Ch.; Campanelli, D.; Zuccotti, A.; Singer, W.; Popelář, Jiří; Gutsche, K.; Geisler, H.S.; Schraven, S.P.; Jaumann, M.; Panford-Walsh, R.; Hu, J.; Schimmang, T.; Zimmermann, U.; Syka, Josef; Knipper, M.

    2016-01-01

    Roč. 53, č. 8 (2016), s. 5607-5627 ISSN 0893-7648 Institutional support: RVO:68378041 Keywords : BDNF * central hyperactivity * high-spontaneous rate Subject RIV: FH - Neurology Impact factor: 6.190, year: 2016

  1. 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.

  2. Amygdala electrical stimulation inducing spatial memory recovery produces an increase of hippocampal bdnf and arc gene expression.

    Science.gov (United States)

    Mercerón-Martínez, D; Almaguer-Melian, W; Alberti-Amador, E; Estupiñán, B; Fernández, I; Bergado, J A

    2016-06-01

    Amygdala seems to promote the consolidation of plastic modification in different brain areas and these long-term brain changes require a rapid de novo RNA and protein synthesis. We have previously shown that basolateral amygdala electrical stimulation produces a partial recovery of spatial memory in fimbria-fornix lesioned animals and it is also able to increase the BDNF protein content in the hippocampus. The emerging question is whether these increased BDNF protein content arises from previously synthesized RNA or from de novo RNA expression. Now we address the question if amygdala electrical stimulation 15min after daily water maze training produces a rapid de novo RNA synthesis in the hippocampus, a critical brain area for spatial memory recovery in fimbria-fornix lesioned animals. In addition, we also study RNA arc expression, a gene which is essential for memory and neural plasticity processes. To this purpose, we study amygdala stimulation effects on the expression of plasticity related-early-genes bdnf and arc in the hippocampus of fimbria-fornix lesioned animals trained in a water-maze for 4days. We also checked on the expression of both genes in non-lesioned, untrained animals (acute condition) at 0.5, 1, 2 and 24h after basolateral amygdala electrical stimulation. Our data from trained animals confirm that daily amygdala electrical stimulation 15min after water maze training produces a partial memory recovery and that is coupled to an increase of bdnf and arc genes expression in the hippocampus. Additionally, the acute study shows that a single session of amygdala stimulation induces a transient increase of both genes (peaking at 30min). These results confirm the memory improving effect of amygdala stimulation in fimbria-fornix-lesioned animals and sustain the assumption that the memory improving effect is mediated by newly synthetized BDNF acting on a memory relevant structure like the hippocampus. The increased amount of BDNF within the hippocampus

  3. Regulated viral BDNF delivery in combination with Schwann cells promotes axonal regeneration through capillary alginate hydrogels after spinal cord injury.

    Science.gov (United States)

    Liu, Shengwen; Sandner, Beatrice; Schackel, Thomas; Nicholson, LaShae; Chtarto, Abdelwahed; Tenenbaum, Liliane; Puttagunta, Radhika; Müller, Rainer; Weidner, Norbert; Blesch, Armin

    2017-09-15

    Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally. In addition, we examined whether SC injection into the caudal spinal parenchyma would further enhance regeneration of descending axons to re-enter the host spinal cord. Our data show that both serotonergic and descending axons traced by biotinylated dextran amine (BDA) extend throughout the scaffolds. The number of regenerating axons is significantly increased when caudal BDNF expression is activated and transient BDNF delivery is able to sustain axons after gene expression is switched off. Descending axons are confined to the caudal graft/host interface even with continuous BDNF expression for 8weeks. Only with a caudal injection of SCs, a pathway facilitating axonal regeneration through the host/graft interface is generated allowing axons to successfully re-enter the caudal spinal cord. Recovery from spinal cord injury is poor due to the limited regeneration observed in the adult mammalian central nervous system. Biomaterials, cell transplantation and growth factors that can guide axons across a lesion site, provide a cellular substrate, stimulate axon growth and have shown some promise in increasing the growth distance of regenerating axons. In the present study, we combined an alginate biomaterial with linear channels with transplantation of Schwann cells within

  4. Serum BDNF levels in relation to illness severity, suicide attempts, and central serotonin activity in patients with major depressive disorder: a pilot study.

    Science.gov (United States)

    Park, Young-Min; Lee, Bun-Hee; Um, Tae Hyun; Kim, Sollip

    2014-01-01

    The aim of this study was to test the hypothesis that serum levels of brain-derived neurotrophic factor (BDNF) are correlated with the loudness dependence of auditory evoked potentials (LDAEP). The question of whether there is a difference in BDNF levels between depressive patients according to their illness severity, history of suicide attempts, and central serotonin activity was also addressed. A sample of 51 patients who met the criteria for major depressive disorder following diagnosis using axis I of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders - text revision comprised the study subjects. The patients were stratified into two subgroups based on their illness severity, history of suicide attempts, and their LDAEP values. The LDAEP was evaluated by measuring the auditory event-related potentials, and serum BDNF was measured using blood sampling before beginning medication with serotonergic agents. There was no difference in serum BDNF levels between the two patient subgroups. The subgroup with moderate-to-severe depression (n = 16) was reanalyzed after stratifying it into two subgroups according to LDAEP and BDNF values (dichotomized at the medians into low and high). The high-LDAEP subgroup had higher serum BDNF levels and total Barratt Impulsiveness Scale score than the low-LDAEP subgroup (p = 0.03 and 0.036, respectively). Serum BDNF levels were positively correlated with LDAEP and total Beck Hopelessness Scale (BHS) score (r = 0.56, p = 0.025, and r = 0.59, p = 0.016, respectively). The high-BDNF subgroup had a higher LDAEP and total BHS score than the low-BDNF subgroup (p = 0.046 and p = 0.011, respectively). This is the first study to demonstrate a relationship between the BDNF level and LDAEP in Asian depressive patients. Intriguingly, the high-BDNF subgroup (divided according to illness severity) exhibited a more severe psychopathology on some psychometric rating scales, a finding that

  5. NGF and BDNF long-term variations in the thyroid, testis and adrenal glands of a mouse model of fetal alcohol spectrum disorders

    OpenAIRE

    Mauro Ceccanti; Sara De Nicolò; Rosanna Mancinelli; George Chaldakov; Valentina Carito; Marco Ceccanti; Giovanni Laviola; Paola Tirassa; Marco Fiore

    2013-01-01

    OBJECTIVES: Fetal Alcohol Spectrum Disorders (FASD) due to prenatal ethanol consumption may induce long-lasting changes to the newborns affecting also the endocrine system and the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) signaling. Thus the aim of this study was to investigate in the thyroid, testis and adrenal glands of a FASD mouse model the long-lasting effects of ethanol exposure during pregnancy and lactation on NGF and BDNF and their main receptors, TrkA an...

  6. Ventricular Septal Defect (For Teens)

    Science.gov (United States)

    ... have a heart defect should avoid getting body piercings. Piercing increases the possibility that bacteria can get into ... damage heart valves. If you're considering a piercing and you have a heart defect, talk to ...

  7. Congenital Heart Defects (For Parents)

    Science.gov (United States)

    ... diagnosed until the teen years — or even adulthood. Newborn Screening Newborns in the U.S. are screened at ... Has a Heart Defect Coarctation of the Aorta Arrhythmias Mitral Valve Prolapse Atrial Septal Defect Ventricular Septal ...

  8. Defects in Quantum Computers.

    Science.gov (United States)

    Gardas, Bartłomiej; Dziarmaga, Jacek; Zurek, Wojciech H; Zwolak, Michael

    2018-03-14

    The shift of interest from general purpose quantum computers to adiabatic quantum computing or quantum annealing calls for a broadly applicable and easy to implement test to assess how quantum or adiabatic is a specific hardware. Here we propose such a test based on an exactly solvable many body system-the quantum Ising chain in transverse field-and implement it on the D-Wave machine. An ideal adiabatic quench of the quantum Ising chain should lead to an ordered broken symmetry ground state with all spins aligned in the same direction. An actual quench can be imperfect due to decoherence, noise, flaws in the implemented Hamiltonian, or simply too fast to be adiabatic. Imperfections result in topological defects: Spins change orientation, kinks punctuating ordered sections of the chain. The number of such defects quantifies the extent by which the quantum computer misses the ground state, and is, therefore, imperfect.

  9. Reconstructions of eyelid defects

    Directory of Open Access Journals (Sweden)

    Nirmala Subramanian

    2011-01-01

    Full Text Available Eyelids are the protective mechanism of the eyes. The upper and lower eyelids have been formed for their specific functions by Nature. The eyelid defects are encountered in congenital anomalies, trauma, and postexcision for neoplasm. The reconstructions should be based on both functional and cosmetic aspects. The knowledge of the basic anatomy of the lids is a must. There are different techniques for reconstructing the upper eyelid, lower eyelid, and medial and lateral canthal areas. Many a times, the defects involve more than one area. For the reconstruction of the lid, the lining should be similar to the conjunctiva, a cover by skin and the middle layer to give firmness and support. It is important to understand the availability of various tissues for reconstruction. One layer should have the vascularity to support the other layer which can be a graft. A proper plan and execution of it is very important.

  10. Long-term Administration of Salicylate-induced Changes in BDNF Expression and CREB Phosphorylation in the Auditory Cortex of Rats.

    Science.gov (United States)

    Yi, Bin; Wu, Cong; Shi, Runjie; Han, Kun; Sheng, Haibin; Li, Bei; Mei, Ling; Wang, Xueling; Huang, Zhiwu; Wu, Hao

    2018-03-01

    We investigated whether salicylate induces tinnitus through alteration of the expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC). Salicylate medication is frequently used for long-term treatment in clinical settings, but it may cause reversible tinnitus. Salicylate-induced tinnitus is associated with changes related to central auditory neuroplasticity. Our previous studies revealed enhanced neural activity and ultrastructural synaptic changes in the central auditory system after long-term salicylate administration. However, the underlying mechanisms remained unclear. Salicylate-induced tinnitus-like behavior in rats was confirmed using gap prepulse inhibition of acoustic startle and prepulse inhibition testing, followed by comparison of the expression levels of BDNF, proBDNF, TrkB, CREB, and p-CREB. Synaptic ultrastructure was observed under a transmission electron microscope. BDNF and p-CREB were upregulated along with ultrastructural changes at the synapses in the AC of rats treated chronically with salicylate (p  0.05). Long-term administration of salicylate increased BDNF expression and CREB activation, upregulated synaptic efficacy, and changed synaptic ultrastructure in the AC. There may be a relationship between these factors and the mechanism of tinnitus.

  11. 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.

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    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.

  12. Disruption of the brain-derived neurotrophic factor (BDNF immunoreactivity in the human Kölliker-Fuse nucleus in victims of unexplained fetal and infant death

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    Anna Maria Lavezzi

    2014-09-01

    Full Text Available Experimental studies have demonstrated that the neurotrophin brain-derived neutrophic factor (BDNF is required for the appropriate development of the central respiratory network, a neuronal complex in the brainstem of vital importance to sustaining life. The pontine Kölliker-Fuse nucleus (KFN is a fundamental component of this circuitry with strong implications in the pre- and postnatal breathing control. This study provides detailed account for the cytoarchitecture, the physiology and the BDNF behaviour of the human KFN in perinatal age. We applied immunohistochemistry in formalin-fixed and paraffin-embedded brainstem samples (from 45 fetuses and newborns died of both known and unknown causes, to analyze BDNF, gliosis and apoptosis patterns of manifestation. The KFN showed clear signs of developmental immaturity, prevalently associated to BDNF altered expression, in high percentages of sudden intrauterine unexplained death syndrome (SIUDS and sudden infant death syndrome (SIDS victims. Our results indicate that BDNF pathway dysfunctions can derange the normal KFN development so preventing the breathing control in the sudden perinatal death.The data presented here are also relevant to a better understanding of how the BDNF expression in the KFN can be involved in several human respiratory pathologies such as the Rett’s and the congenital central hypoventilation syndromes.

  13. Inhibition of BDNF in multiple myeloma blocks osteoclastogenesis via down-regulated stroma-derived RANKL expression both in vitro and in vivo.

    Science.gov (United States)

    Ai, Li-Sha; Sun, Chun-Yan; Zhang, Lu; Zhou, Shun-Chang; Chu, Zhang-Bo; Qin, You; Wang, Ya-Dan; Zeng, Wei; Yan, Han; Guo, Tao; Chen, Lei; Yang, Di; Hu, Yu

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) was recently identified as a factor produced by multiple myeloma (MM) cells, which may contribute to bone resorption and disease progression in MM, though the molecular mechanism of this process is not well understood. The purpose of this study was to test the effect of BDNF on bone disease and growth of MM cells both in vitro and in vivo. Co- and triple-culture systems were implemented. The in vitro results demonstrate that BDNF augmented receptor activator of nuclear factor kappa B ligand (RANKL) expression in human bone marrow stromal cells, thus contributing to osteoclast formation. To further clarify the effect of BDNF on myeloma bone disease in vivo, ARH-77 cells were stably transfected with an antisense construct to BDNF (AS-ARH) or empty vector (EV-ARH) to test their capacity to induce MM bone disease in SCID-rab mice. Mice treated with AS-ARH cells were preserved, exhibited no radiologically identifiable lytic lesions and, unlike the controls treated with EV-ARH cells, lived longer and showed reduced tumor burden. Consistently, bones harboring AS-ARH cells showed marked reductions of RANKL expression and osteoclast density compared to the controls harboring EV-ARH cells. These results provide further support for the potential osteoclastogenic effects of BDNF, which may mediate stromal-MM cell interactions to upregulate RANKL secretion, in myeloma bone diseases.

  14. BDNF prevents NMDA-induced toxicity in models of Huntington's disease: the effects are genotype specific and adenosine A2A receptor is involved.

    Science.gov (United States)

    Martire, Alberto; Pepponi, Rita; Domenici, Maria Rosaria; Ferrante, Antonella; Chiodi, Valentina; Popoli, Patrizia

    2013-04-01

    NMDA receptor-mediated excitotoxicity is thought to play a pivotal role in the pathogenesis of Huntington's disease (HD). The neurotrophin brain-derived neurotrophic factor (BDNF), which is also highly involved in HD and whose effects are modulated by adenosine A2 ARs, influences the activity and expression of striatal NMDA receptors. In electrophysiology experiments, we investigated the role of BDNF toward NMDA-induced effects in HD models, and the possible involvement of A2ARs. In corticostriatal slices from wild-type mice and age-matched symptomatic R6/2 mice (a model of HD), NMDA application (75 μM) induced a transient or a permanent (i.e., toxic) reduction of field potential amplitude, respectively. BDNF (10 ng/mL) potentiated NMDA effects in wild-type, while it protected from NMDA toxicity in R6/2 mice. Both effects of BDNF were prevented by A2 AR blockade. The protective effect of BDNF against NMDA-induced toxicity was reproduced in a cellular model of HD. These findings may have very important implications for the neuroprotective potential of BDNF and A2 AR ligands in HD. © 2013 International Society for Neurochemistry.

  15. Role of Adenosine A2A Receptors in Modulating Synaptic Functions and Brain Levels of BDNF: a Possible Key Mechanism in the Pathophysiology of Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Maria Teresa Tebano

    2010-01-01

    Full Text Available In the last few years, accumulating evidence has shown the existence of an important cross-talk between adenosine A2A receptors (A2ARs and brain-derived neurotrophic factor (BDNF. Not only are A2ARs involved in the mechanism of transactivation of BDNF receptor TrkB, they also modulate the effect of BDNF on synaptic transmission, playing a facilitatory and permissive role. The cAMP-PKA pathway, the main transduction system operated by A2ARs, is involved in such effects. Furthermore, a basal tonus of A2ARs is required to allow the regulation of BDNF physiological levels in the brain, as demonstrated by the reduced protein levels measured in A2ARs KO mice. The crucial role of adenosine A2ARs in the maintenance of synaptic functions and BDNF levels will be reviewed here and discussed in the light of possible implications for Huntington's disease therapy, in which a joint impairment of BDNF and A2ARs seems to play a pathogenetic role.

  16. Benign gastric filling defect

    Energy Technology Data Exchange (ETDEWEB)

    Oh, K. K.; Lee, Y. H.; Cho, O. K.; Park, C. Y. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  17. Benign gastric filling defect

    International Nuclear Information System (INIS)

    Oh, K. K.; Lee, Y. H.; Cho, O. K.; Park, C. Y.

    1979-01-01

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  18. Effect of Early-Life Fluoxetine on Anxiety-Like Behaviors in BDNF Val66Met Mice.

    Science.gov (United States)

    Dincheva, Iva; Yang, Jianmin; Li, Anfei; Marinic, Tina; Freilingsdorf, Helena; Huang, Chienchun; Casey, B J; Hempstead, Barbara; Glatt, Charles E; Lee, Francis S; Bath, Kevin G; Jing, Deqiang

    2017-12-01

    Adolescence is a developmental stage in which the incidence of psychiatric disorders, such as anxiety disorders, peaks. Selective serotonin reuptake inhibitors (SSRIs) are the main class of agents used to treat anxiety disorders. However, the impact of SSRIs on the developing brain during adolescence remains unknown. The authors assessed the impact of developmentally timed SSRI administration in a genetic mouse model displaying elevated anxiety-like behaviors. Knock-in mice containing a common human single-nucleotide polymorphism (Val66Met; rs6265) in brain-derived neurotrophic factor (BDNF), a growth factor implicated in the mechanism of action of SSRIs, were studied based on their established phenotype of increased anxiety-like behavior. Timed administration of fluoxetine was delivered during one of three developmental periods (postnatal days 21-42, 40-61, or 60-81), spanning the transition from childhood to adulthood. Neurochemical and anxiety-like behavioral analyses were performed. We identified a "sensitive period" during periadolescence (postnatal days 21-42) in which developmentally timed fluoxetine administration rescued anxiety-like phenotypes in BDNF Val66Met mice in adulthood. Compared with littermate controls, BDNF Met/Met mice exhibited diminished maturation of serotonergic fibers projecting particularly to the prefrontal cortex, as well as decreased expression of the serotonergic trophic factor S100B in the dorsal raphe. Interestingly, deficient serotonergic innervation, as well as S100B levels, were rescued with fluoxetine administration during periadolescence. These findings suggest that SSRI administration during a "sensitive period" during periadolescence leads to long-lasting anxiolytic effects in a genetic mouse model of elevated anxiety-like behaviors. These persistent effects highlight the role of BDNF in the maturation of the serotonin system and the capacity to enhance its development through a pharmacological intervention.

  19. 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

  20. Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to induce sex specific visceral hypersensitivity in offspring

    Science.gov (United States)

    Winston, John H.; Li, Qingjie; Sarna, Sushil K.

    2014-01-01

    Background Irritable bowel syndrome (IBS) is a heterogeneous disorder with abdomen pain as one of the primary symptoms. The etiology of IBS remains unknown. Epidemiological studies found that a subset of these patients have a history of adverse early-life events. We tested the hypothesis that chronic prenatal stress (CPS) epigenetically enhances brain-derived neurotrophic factor (BDNF) in spinal cord to aggravate colon sensitivity to colorectal distension (CRD) differentially in male and female offspring. Methods We used heterotypic intermittent chronic stress (HeICS) protocols in pregnant dams from E11 until delivery. Results CPS induced significant visceral hypersensitivity (VHS) to CRD in male and female offspring. A second exposure to HeICS in adult offspring exacerbated VHS greater in female offspring that persisted longer than in male offspring. CPS upregulated BDNF expression in the lumbar-sacral dorsal horn that correlated with the exacerbation of VHS in female, but not in male offspring. The upregulation of BDNF was due to a significant increase in RNA Pol II binding, histone H3 acetylation and significant decrease in histone deacetylase 1 association with the core promoter of BDNF in female offspring. Other chronic prenatal and neonatal stress protocols were less effective than HeICS. Conclusion & Inferences The development of visceral hypersensitivity, which contributes to the symptom of intermittent abdominal pain, is a two-step process, chronic in utero stress followed by chronic stress in adult-life. This two-step process induces aggravated and persistent colon hypersensitivity in female than in male offspring. Our preclinical model explains several clinical features in IBS patients. PMID:24588943

  1. The Effects of Resistance Exercise on Cocaine Self-Administration, Muscle Hypertrophy, and BDNF Expression in the Nucleus Accumbens

    Science.gov (United States)

    Strickland, Justin C.; Abel, Jean M.; Lacy, Ryan T.; Beckmann, Joshua S.; Witte, Maryam A.; Lynch, Wendy J.; Smith, Mark A.

    2016-01-01

    Background Exercise is associated with positive outcomes in drug abusing populations and reduces drug self-administration in laboratory animals. To date, most research has focused on aerobic exercise, and other types of exercise have not been examined. This study examined the effects of resistance exercise (strength training) on cocaine self-administration and BDNF expression, a marker of neuronal activation regulated by aerobic exercise. Methods Female rats were assigned to either exercising or sedentary conditions. Exercising rats climbed a ladder wearing a weighted vest and trained six days/week. Training consisted of a three-set “pyramid” in which the number of repetitions and resistance varied across three sets: eight climbs carrying 70% body weight (BW), six climbs carrying 85% BW, and four climbs carrying 100% BW. Rats were implanted with intravenous catheters and cocaine self-administration was examined. Behavioral economic measures of demand intensity and demand elasticity were derived from the behavioral data. BDNF mRNA expression was measured via qRT-PCR in the nucleus accumbens following behavioral testing. Results Exercising rats self-administered significantly less cocaine than sedentary rats. A behavioral economic analysis revealed that exercise increased demand elasticity for cocaine, reducing consumption at higher unit prices. Exercising rats had lower BDNF expression in the nucleus accumbens core than sedentary rats. Conclusions These data indicate that resistance exercise decreases cocaine self-administration and reduces BDNF expression in the nucleus accumbens after a history of cocaine exposure. Collectively, these findings suggest that strength training reduces the positive reinforcing effects of cocaine and may decrease cocaine use in human populations. PMID:27137405

  2. The Effects of Endurance Training and Gallic Acid on BDNF and TNF-a in Male Rats with Alzheimer

    Directory of Open Access Journals (Sweden)

    Yoones Baziyar

    2017-01-01

    Full Text Available Background: In the present study, the effects of endurance training and chronic administration of Gallic acid (GA on hippocampal level of brain-derived neurotrophic factor (BDNF and tumor necrosis factor alpha (TNF-α in trimethyltin (TMT-induced hippocampal degeneration as a model of Alzheimer’s disease were investigated. Methods: 70 male Sprague-Dawley rats were selected and randomly assigned to 7 groups: 1.control, 2.TMT, 3.TMT+GA50, 4.TMT+GA100, 5.TMT+Ex, 6.TMT+Ex+GA50, 7.TMT+Ex+GA100. For induction of Alzheimer's disease, the rats in groups 2-7 were injected with single dose of TMT (8 mg/kg, intra-peritonealy (i.p.. Rats in the groups 5, 6 and 7 carried out an 8-week exercise program on a motorized treadmill (15-20 m/min, 0% inclination for 15-30 min/day, 5 days/week.  In addition, the groups 3 and 6 were treated by 50 mg /kg and groups 4 and 7 are administered 100 mg/ kg of Gallic acid for 2 weeks. Then, the hippocampal level of BDNF and TNF-α was performed for all groups by Elisa.  Results: The findings of present study showed that the hippocampal level of BDNF in all test groups are significantly higher than TMT group (p≤0.05 and the hippocampal level of TNF-a in all test groups is significantly less than the TMT group (p≤0.05. Conclusion: Endurance exercises training, chronic administration of GA and co-treatment with training and GA consumption specially, having sufficient neurotrophic and immune modulator effects in male rats with Alzheimer.  Keywords: Alzheimer’s disease, Endurance training, Gallic acid, BDNF, TNF-a, hippocampus 

  3. BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity.

    Science.gov (United States)

    Notaras, Michael J; Hill, Rachel A; Gogos, Joseph A; van den Buuse, Maarten

    2017-05-01

    Reduced expression of Brain-Derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of schizophrenia. The BDNF Val66Met polymorphism, which results in deficient activity-dependent secretion of BDNF, is associated with clinical features of schizophrenia. We investigated the effect of this polymorphism on Prepulse Inhibition (PPI), a translational model of sensorimotor gating which is disrupted in schizophrenia. We utilized humanized BDNFVal66Met (hBDNFVal66Met) mice which have been modified to carry the Val66Met polymorphism, as well as express humanized BDNF in vivo. We also studied the long-term effect of chronic corticosterone (CORT) exposure in these animals as a model of history of stress. PPI was assessed at 30ms and 100ms interstimulus intervals (ISI). Analysis of PPI at the commonly used 100ms ISI identified that, irrespective of CORT treatment, the hBDNFVal/Met genotype was associated with significantly reduced PPI. In contrast, PPI was not different between hBDNFMet/Met and hBDNFVal/Val genotype mice. At the 30ms ISI, CORT treatment selectively disrupted sensorimotor gating of hBDNFVal/Met heterozygote mice but not hBDNFVal/Val or hBDNFMet/Met mice. Analysis of startle reactivity revealed that chronic CORT reduced startle reactivity of hBDNFVal/Val male mice by 51%. However, this was independent of the effect of CORT on PPI. In summary, we provide evidence of a distinct BDNFVal66Met heterozygote-specific phenotype using the sensorimotor gating endophenotype of schizophrenia. These data have important implications for clinical studies where, if possible, the BDNFVal/Met heterozygote genotype should be distinguished from the BDNFMet/Met genotype. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. BDNF Val66Met genotype and neuroticism predict life stress: A longitudinal study from childhood to adulthood.

    Science.gov (United States)

    Lehto, Kelli; Mäestu, Jarek; Kiive, Evelyn; Veidebaum, Toomas; Harro, Jaanus

    2016-03-01

    The brain-derived neurotrophic factor gene (BDNF) Val66Met polymorphism and life stress have been associated with negative emotionality (e.g., neuroticism), but relevant evidence is far from unequivocal. Possible confounding factors include the type and timing of stressful events measured, such as childhood adversity vs. recent stressful events, and variable gene × environment interactions. The aim of this study was to longitudinally assess the BDNF Val66Met polymorphism and environment interaction effect on neuroticism in a population representative sample, depending upon the type of stress, gender and family relations. In the original older cohort of the Estonian Children Personality Behavior and Health Study (ECPBHS, n=593), neuroticism was measured at age 15 (parental assessment), 18 and 25 (self-assessments). Childhood stress was reported at age 15, quality of family relations was measured at age 18, and recent stressful life events at age 25. The BDNF Val66Met polymorphism interacted with recent stressful life events, but not with childhood adversities, to impact neuroticism. Interestingly, in female participants, neuroticism at age 18 predicted future stressful life events dependent upon genotype: individuals with Val/Val genotype and high neuroticism experienced higher, but Met-allele carriers with high neuroticism lower stress exposure at age 25. Similar tendencies were observed using parental assessments at age 15. The protective effect of Met-allele in the high stress exposure group could result from better early family environment. In conclusion, we herewith provide further evidence for a role of BDNF gene variance contributing to plasticity in response to environmental demands. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  5. Thermal properties of defective fullerene

    Science.gov (United States)

    Li, Jian; Zheng, Dong-Qin; Zhong, Wei-Rong

    2016-09-01

    We have investigated the thermal conductivity of defective fullerene (C60) by using the nonequilibrium molecular dynamics (MD) method. It is found that the thermal conductivity of C60 with one defect is lower than the thermal conductivity of perfect C60. However, double defects in C60 have either positive or negative influence on the thermal conductivity, which depends on the positions of the defects. The phonon spectra of perfect and defective C60 are also provided to give corresponding supports. Our results can be extended to long C60 chains, which is helpful for the thermal management of C60.

  6. Impaired cognitive flexibility during sleep deprivation among carriers of the Brain Derived Neurotrophic Factor (BDNF) Val66Met allele.

    Science.gov (United States)

    Grant, Leilah K; Cain, Sean W; Chang, Anne-Marie; Saxena, Richa; Czeisler, Charles A; Anderson, Clare

    2018-02-15

    Accumulating evidence points to a genetic contribution to explain inter-individual vulnerability to sleep deprivation. A functional polymorphism in the BDNF gene, which causes a valine (Val) to methionine (Met) amino acid substitution at Codon 66, has been associated with cognitive impairment, particularly in populations with impaired frontal functioning. We hypothesised that sleep deprivation, which affects frontal function, may lead to cognitive dysfunction in Met allele carriers. To examine this, we investigated, in different BDNF genotypes, the effects of sleep deprivation on cognitive flexibility, as measured by response inhibition using the Stroop Color Naming Task. Thirty healthy, adults of European ancestry, including 12 heterozygous Met allele carriers and 18 Val/Val homozygotes, underwent 30-h of extended wakefulness under constant routine conditions. A computerised Stroop task was administered every 2h. Error rate and reaction times increased with time awake for all individuals. Participants with the Val/Met genotype made more errors on incongruent trials after 20h awake. While Val/Met participants also took significantly longer to respond when inhibiting a prepotent response irrespective of time awake, this was particularly evident during the biological night. Our study shows that carriers of the BDNF Met allele are more vulnerable to the impact of prolonged wakefulness and the biological night on a critical component of executive function, as measured by response inhibition on the Stroop task. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Acute exercise has a general facilitative effect on cognitive function: A combined ERP temporal dynamics and BDNF study.

    Science.gov (United States)

    Chang, Yu-Kai; Alderman, Brandon L; Chu, Chien-Heng; Wang, Chun-Chih; Song, Tai-Fen; Chen, Feng-Tzu

    2017-02-01

    This study examined whether acute moderate intensity exercise results in a general or selective improvement in cognitive function. In addition, multiple stimulus-locked ERP components and serum BDNF levels were assessed to investigate potential neurobiological mechanisms underlying acute exercise effects on select aspects of cognitive performance. Thirty young adults were recruited and participated in exercise and reading control sessions in a counterbalanced order. Following treatments, the Stroop task was administrated, and N1, N2, P3, and N450 components of the ERP waveform were recorded and analyzed. Additionally, blood samples were withdrawn immediately following exercise or rest conditions prior to administration of the Stroop task. Acute exercise facilitated response times for both Stroop congruent and incongruent task conditions, with a similar magnitude of improvement. Larger P3 and reduced N450 amplitudes as well as decreased N450 latency were observed following exercise, but no effects on N1 and N2 components were found. This dose of exercise also did not influence serum BDNF levels. These findings suggest that moderate intensity acute exercise results in a generalized rather than selective improvement in cognition. The facilitation may be related to an increase in attentional or neural resource allocation and conflict detection processes reflected by longer latency endogenous components (P3, N450), but is not influenced by earlier sensory and monitoring processes revealed by earlier ERP components or by serum levels of BDNF. © 2016 Society for Psychophysiological Research.

  8. The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model.

    Science.gov (United States)

    Zhang, Leilei; Li, Zhi; Chen, Jie; Li, Xinying; Zhang, Jianxin; Belsky, Jay

    2016-03-01

    Although depressive symptoms are common during adolescence, little research has examined gene-environment interaction on youth depression. This study chose the brain-derived neurotrophic factor (BDNF) gene, tested the interaction between a functional polymorphism resulting amino acid substitution of valine (Val) to methionine (Met) in the proBDNF protein at codon 66 (Val66Met), and maternal parenting on youth depressive symptoms in a sample of 780 community adolescents of Chinese Han ethnicity (aged 11-17, M = 13.6, 51.3 % females). Participants reported their depressive symptoms and perceived maternal parenting. Results indicated the BDNF Val66Met polymorphism significantly moderated the influence of maternal warmth-reasoning, but not harshness-hostility, on youth depressive symptoms. Confirmatory model evaluation indicated that the interaction effect involving warmth-reasoning conformed to the differential-susceptibility rather than diathesis-stress model of person-X-environment interaction. Thus, Val carriers experienced less depressive symptoms than Met homozygotes when mothering was more positive but more symptoms when mothering was less positive. The findings provided evidence in support of the differential susceptibility hypothesis of youth depressive symptoms and shed light on the importance of examining the gene-environment interaction from a developmental perspective.

  9. Lipopolysaccharide causes deficits in spatial learning in the watermaze but not in BDNF expression in the rat dentate gyrus.

    Science.gov (United States)

    Shaw, K N; Commins, S; O'Mara, S M

    2001-09-28

    We investigated the effects of a single injection and a daily injection of lipopolysaccharide (LPS) on spatial learning and brain-derived neurotrophic factor (BDNF) expression in the rat dentate gyrus. LPS is derived from the cell wall of Gram-negative bacteria and is a potent endotoxin that causes the release of cytokines such as interleukin-1 and tumour necrosis factor. LPS is thought to activate both the neuroimmune and neuroendocrine systems; it also blocks long-term potentiation in the hippocampus. Here, we examined the effects of LPS on a form of hippocampal-dependent learning-spatial learning in the water maze. Rats were injected with LPS intraperitoneally (100 microg/kg) and trained in the water maze. The first group of rats were injected on day 1 of training, 4 h prior to learning the water maze task. Groups 2 and 3 were injected daily, again 4 h prior to the water-maze task; group 2 with LPS and group 3 with saline. A number of behavioural variables were recorded by a computerised tracking system for each trial. The behavioural results showed a single injection of LPS (group 1) impaired escape latency in both the acquisition and retention phases of the study, whereas a daily injection of LPS did not significantly impair acquisition or retention. BDNF expression was analysed in the dentate gyrus of all animals. No significant differences in BDNF expression were found between the three groups.

  10. Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: A meta-analysis study.

    Science.gov (United States)

    Rocha, Renan Boeira; Dondossola, Eduardo Ronconi; Grande, Antônio José; Colonetti, Tamy; Ceretta, Luciane Bisognin; Passos, Ives C; Quevedo, Joao; da Rosa, Maria Inês

    2016-12-01

    We performed a systematic review and meta-analysis to estimate brain-derived neurotrophic factor (BDNF) level in patients with major depressive disorder (MDD) after electroconvulsive therapy (ECT). A comprehensive search of the Cochrane Library, MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published from January 1990 to April 2016. The following key terms were searched: "major depressive disorder", "unipolar depression", "brain-derived neurotrophic factor", and "electroconvulsive therapy". A total of 252 citations were identified by the search strategy, and nine studies met the inclusion criteria of the meta-analysis. BDNF levels were increased among patients with MDD after ECT (P value = 0.006). The standardized mean difference was 0.56 (95% CI: 0.17-0.96). Additionally, we found significant heterogeneity between studies (I 2  = 73%). Our findings suggest a potential role of BDNF as a marker of treatment response after ECT in patients with MDD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Piperine-like alkamides from Piper nigrum induce BDNF promoter and promote neurite outgrowth in Neuro-2a cells.

    Science.gov (United States)

    Yun, Young Sook; Noda, Sachie; Takahashi, Shigeru; Takahashi, Yuji; Inoue, Hideshi

    2018-01-01

    Black pepper (Piper nigrum) contains a variety of alkamides. Among them, piperine has been reported to have antidepressant-like effects in chronically stressed mice, but little is known about the biological activity of other alkamides. In this study, we investigated the effects of alkamides from white pepper (P. nigrum) on neuronal cells. Twelve alkamides were isolated from white pepper MeOH extracts, and their chemical structures were identified by NMR and MS analyses. The compounds were subjected to assays using the luciferase-reporter gene under the control of the BDNF promoter or cAMP response element in mouse neuroblastoma Neuro-2a cells. In both assays, marked reporter-inducing activity was observed for piperine (1), piperettine (2) and piperylin (7), all of which have in common an (E)-5-(buta-1,3-dien-1-yl)benzo[d] [1, 3] dioxole moiety. Piperettine (2) and piperylin (7) tended to increase endogenous BDNF protein levels. Furthermore, piperylin (7) promoted retinoic acid-induced neurite outgrowth. These results suggest that piperylin (7), or analogues thereof, may have a beneficial effect on disorders associated with dysregulation of BDNF expression, such as depression.

  12. Sleep deprivation prevents stimulation-induced increases of levels of P-CREB and BDNF: protection by caffeine.

    Science.gov (United States)

    Alhaider, Ibrahim A; Aleisa, Abdulaziz M; Tran, Trinh T; Alkadhi, Karim A

    2011-04-01

    It is well known that caffeine and sleep deprivation have opposing effects on learning and memory; therefore, this study was undertaken to determine the effects of chronic (4wks) caffeine treatment (0.3g/l in drinking water) on long-term memory deficit associated with 24h sleep deprivation. Animals were sleep deprived using the modified multiple platform method. The results showed that chronic caffeine treatment prevented the impairment of long-term memory as measured by performance in the radial arm water maze task and normalized L-LTP in area CA1 of the hippocampi of sleep-deprived anesthetized rats. Sleep deprivation prevents the high frequency stimulation-induced increases in the levels of phosphorylated-cAMP response element binding protein (P-CREB) and brain-derived neurotrophic factor (BDNF) seen during the expression of late phase long-term potentiation (L-LTP). However, chronic caffeine treatment prevented the effect of sleep-deprivation on the stimulated levels of P-CREB and BDNF. The results suggest that chronic caffeine treatment may protect the sleep-deprived brain probably by preserving the levels of P-CREB and BDNF. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. COMT (Val158Met and BDNF (Val66Met Genes Polymorphism in Schizophrenia: A Case-Control Report

    Directory of Open Access Journals (Sweden)

    ramin saravani

    2017-10-01

    Full Text Available Objective: The effects of human brain-derived neurotropic factor (BDNF Val66Met (G>A and the human Catechol-O-methylTransferase (COMT Val158Met (G>A polymorphisms on Schizophrenia (SCZ risk were evaluated.Methods: This case control study included 92 SCZ patients and 92 healthy controls (HCs. Genotyping of both variants were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR.Results: The findings showed that BDNF Val66Met (G>A variant increased the risk of SCZ (OR=2.008 95%CI=1.008-4.00, P=0.047, GA vs. GG, OR=3.876 95%CI=1.001-14.925, P=0.049. AA vs. GG, OR=2.272. 95%CI=1.204-4.347, P=0.011, GA+AA vs. GG, OR=2.22 95%CI=1.29-3.82. P=0.005, A vs. G. COMT Val158Met (G>A polymorphism was not associated with the risk/protective of SCZ.Conclusion: The results proposed that BDNF Val66Met (G>A polymorphism may increase the risk of SCZ development and did not support an association between COMT Val158Met (G>A variant and risk/protective of SCZ. Further studies and different ethnicities are recommended to confirm the findings.

  14. Muscle Contraction Regulates BDNF/TrkB Signaling to Modulate Synaptic Function through Presynaptic cPKCα and cPKCβI

    Directory of Open Access Journals (Sweden)

    Erica Hurtado

    2017-05-01

    Full Text Available The neurotrophin brain-derived neurotrophic factor (BDNF acts via tropomyosin-related kinase B receptor (TrkB to regulate synapse maintenance and function in the neuromuscular system. The potentiation of acetylcholine (ACh release by BDNF requires TrkB phosphorylation and Protein Kinase C (PKC activation. BDNF is secreted in an activity-dependent manner but it is not known if pre- and/or postsynaptic activities enhance BDNF expression in vivo at the neuromuscular junction (NMJ. Here, we investigated whether nerve and muscle cell activities regulate presynaptic conventional PKC (cPKCα and βI via BDNF/TrkB signaling to modulate synaptic strength at the NMJ. To differentiate the effects of presynaptic activity from that of muscle contraction, we stimulated the phrenic nerve of rat diaphragms (1 Hz, 30 min with or without contraction (abolished by μ-conotoxin GIIIB. Then, we performed ELISA, Western blotting, qRT-PCR, immunofluorescence and electrophysiological techniques. We found that nerve-induced muscle contraction: (1 increases the levels of mature BDNF protein without affecting pro-BDNF protein or BDNF mRNA levels; (2 downregulates TrkB.T1 without affecting TrkB.FL or p75 neurotrophin receptor (p75 levels; (3 increases presynaptic cPKCα and cPKCβI protein level through TrkB signaling; and (4 enhances phosphorylation of cPKCα and cPKCβI. Furthermore, we demonstrate that cPKCβI, which is exclusively located in the motor nerve terminals, increases activity-induced acetylcholine release. Together, these results show that nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling pathway, retrogradely activating presynaptic cPKC isoforms (in particular cPKCβI to modulate synaptic function. These results indicate that a decrease in neuromuscular activity, as occurs in several neuromuscular disorders, could affect the BDNF/TrkB/PKC pathway that links pre- and postsynaptic activity to maintain neuromuscular function.

  15. Effects of ionizing-radiation to the expressions of bFGF and BDNF and the protective and repaired functions of melatonin in the forebrain of rat

    International Nuclear Information System (INIS)

    Di Rongke; Xu Jin; Zhou Zhiqiang; Liu Yiren

    2006-01-01

    Objective: To investigate the expressions of bFGF and BDNF induced with ionizing-radiation and the effects of melatonin to the expressions of bFGF and BDNF in the rate cerebral cortex and subependymal ventrical zone (SVZ) and discuss the protective function and repaired mechanism of melatonin to brain during radiation nervous damage. Methods: 60 SD rats were used in this experiment, which were divided into three groups: blank control group, radiation control group, and treatment groups. Injections of melatonin were given into the abdomen of the rats in the treatment group in three doses of 1, 5 and 10 mg·kg -1 one time each day, in total of 10 days. Then, the radiation control and treatment groups were X-rayed a dose of 600 cGy. All of rat brains were cut up in coronal sections continuously, which were stained with bFGF and BDNF in immunohistochemical ABC method. The positive cells stained with bFGF and BDNF were observed and counted under the light microscope with computed program. Results: bFGF and BDNF are expressed weakly in cerebral cortex and subependymal ventrical zone of the normal rats. One day after radiation, the expressions of bFGF and BDNF are increasing, but weaking 5 days after radiation in cerebral cortex; then, one day after radiation, the expressions of bFGF and BDNF are less increasing, but more increasing 5 days after radiation in the subependymal ventrical zone cells. When the rats were treated by the melatonin in advance, the expressions of bFGF and BDNF are increasing continuously (more than 50%) and accompanying with the dose of melatonin. The cells of proliferation, differentiation, and migration can be observed in the subependymal ventrical zone (from 1-2 layers to 3-5 layers). Conclution: Radiation nervous damage can induce the expressions of bFGF and BDNF in the cerebral cortex and subependymal ventrical zone, which are more increasing when stimulated with melatonin. It is shown that melatonin has the functions to protect the cerebral

  16. Point defects in nickel

    International Nuclear Information System (INIS)

    Peretto, P.

    1969-01-01

    The defects in electron irradiated nickel (20 deg. K) or neutron irradiated nickel (28 deg. K) are studied by simultaneous analysis using the magnetic after-effect, electron microscopy and electrical resistivity recovery. We use zone refined nickel (99.999 per cent) which, for some experiments, is alloyed with a small amount of iron (for example 0.1 per cent Fe). The temperature dependant electrical recovery may be divided in four stages. The sub-stages I B (31 deg. K), I C (42 deg. K), I D (from to 57 deg. K) and I E (62 deg. K) of stage I are due to the disappearance of single interstitials into vacancies. The interstitial defect has a split configuration with a migration energy of about 0.15 eV. In the close pair which disappears in stage I B the interstitial is found to be in a 3. neighbour position whilst in stage I D it is near the direction from the vacancy. In stage I E there is no longer any interaction between the interstitial and the vacancy. The stage II is due to more complicated interstitial defects: di-interstitials for stage II B (84 deg. K) and larger and larger interstitial loops for the following sub-stages. The loops may be seen by electron microscopy. Impurities can play the role of nucleation centers for the loops. Stages III A (370 deg. K) and III B (376 deg. K) are due to two types of di-vacancies. During stage IV (410 deg. K) the single vacancies migrate. Vacancy type loops and interstitial type loops grow concurrently and disappear at about 800 deg. K as observed by electron microscopy. (author) [fr

  17. Single ventricle cardiac defect

    International Nuclear Information System (INIS)

    Eren, B.; Turkmen, N.; Fedakar, R.; Cetin, V.

    2010-01-01

    Single ventricle heart is defined as a rare cardiac abnormality with a single ventricle chamber involving diverse functional and physiological defects. Our case is of a ten month-old baby boy who died shortly after admission to the hospital due to vomiting and diarrhoea. Autopsy findings revealed cyanosis of finger nails and ears. Internal examination revealed; large heart, weighing 60 grams, single ventricle, without a septum and upper membranous part. Single ventricle is a rare pathology, hence, this paper aims to discuss this case from a medico-legal point of view. (author)

  18. Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor (BDNF) tohuman umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) promotescrush-injured rat sciatic nerve regeneration.

    Science.gov (United States)

    Hei, Wei-Hong; Almansoori, Akram A; Sung, Mi-Ae; Ju, Kyung-Won; Seo, Nari; Lee, Sung-Ho; Kim, Bong-Ju; Kim, Soung-Min; Jahng, Jeong Won; He, Hong; Lee, Jong-Ho

    2017-03-16

    This study was designed toinvestigate the efficacy of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) in a rat sciatic nerve crush injury model. BDNF protein and mRNA expression after infection was checked through an enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Male Sprague-Dawley rats (200-250g, 6 weeks old) were distributed into threegroups (n=20 each): the control group, UCB-MSC group, and BDNF-adenovirus infected UCB-MSC (BDNF-Ad+UCB-MSC) group. UCB-MSCs (1×10 6 cells/10μl/rat) or BDNF-Ad+UCB-MSCs (1×10 6 cells/10μl/rat)were transplantedinto the rats at the crush site immediately after sciatic nerve injury. Cell tracking was done with PKH26-labeled UCB-MSCs and BDNF-Ad+UCB-MSCs (1×10 6 cells/10μl/rat). The rats were monitored for 4 weeks post-surgery. Results showed that expression of BDNF at both the protein and mRNA levels was higher inthe BDNF-Ad+UCB-MSC group compared to theUCB-MSC group in vitro.Moreover, BDNF mRNA expression was higher in both UCB-MSC group and BDNF-Ad+ UCB-MSC group compared tothe control group, and BDNF mRNA expression in theBDNF-Ad+UCB-MSC group was higher than inboth other groups 5days after surgeryin vivo. Labeled neurons in the dorsal root ganglia (DRG), axon counts, axon density, and sciatic function index were significantly increased in the UCB-MSC and BDNF-Ad+ UCB-MSCgroupscompared to the controlgroup four weeksaftercell transplantation. Importantly,the BDNF-Ad+UCB-MSCgroup exhibited more peripheral nerve regeneration than the other two groups.Our results indicate thatboth UCB-MSCs and BDNF-Ad+UCB-MSCscan improve rat sciatic nerve regeneration, with BDNF-Ad+UCB-MSCsshowing a greater effectthan UCB-MSCs. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effects of Environmental Enrichment on Doublecortin and BDNF Expression along the Dorso-Ventral Axis of the Dentate Gyrus

    Directory of Open Access Journals (Sweden)

    Fabio Gualtieri

    2017-09-01

    Full Text Available Adult hippocampal neurogenesis (AHN in the dentate gyrus is known to respond to environmental enrichment, chronic stress, and many other factors. The function of AHN may vary across the septo-temporal axis of the hippocampus, as different subdivisions are responsible for different functions. The dorsal pole regulates cognitive-related behaviors, while the ventral pole mediates mood-related responses through the hypothalamic-pituitary-adrenal (HPA axis. In this study, we investigate different methods of quantifying the effect of environmental enrichment on AHN in the dorsal and ventral parts of the dentate gyrus (dDG and vDG. To this purpose, 11-week-old female CD-1 mice were assigned for 8 days to one of two conditions: the Environmental Enrichment (E group received (i running wheels, (ii larger cages, (iii plastic tunnels, and (iv bedding with male urine, while the Control (C group received standard housing. Dorsal CA (Cornu Ammonis and DG regions were larger in the E than the C animals. Distance run linearly predicted the volume of the dorsal hippocampus, as well as of the intermediate and ventral CA regions. In the dDG, the amount of Doublecortin (DCX immunoreactivity was significantly higher in E than in C mice. Surprisingly, this pattern was the opposite in the vDG (C > E. Real-time PCR measurement of Dcx mRNA and DCX protein analysis using ELISA showed the same pattern. Brain Derived Neurotrophic Factor (BDNF immunoreactivity and mRNA displayed no difference between E and C, suggesting that upregulation of DCX was not caused by changes in BDNF levels. BDNF levels were higher in vDG than in dDG, as measured by both methods. Bdnf expression in vDG correlated positively with the distance run by individual E mice. The similarity in the patterns of immunoreactivity, mRNA and protein for differential DCX expression and for BDNF distribution suggests that the latter two methods might be effective tools for more rapid quantification of AHN.

  20. Social isolation mediated anxiety like behavior is associated with enhanced expression and regulation of BDNF in the female mouse brain.

    Science.gov (United States)

    Kumari, Anita; Singh, Padmanabh; Baghel, Meghraj Singh; Thakur, M K

    2016-05-01

    Adverse early life experience is prominent risk factors for numerous psychiatric illnesses, including mood and anxiety disorders. It imposes serious long-term costs on the individual as well as health and social systems. Hence, developing therapies that prevent the long-term consequences of early life stress is of utmost importance, and necessitates a better understanding of the mechanisms by which early life stress triggers long-lasting alterations in gene expression and behavior. Post-weaning isolation rearing of rodents models the behavioral consequences of adverse early life experiences in humans and it is reported to cause anxiety like behavior which is more common in case of females. Therefore, in the present study, we have studied the impact of social isolation of young female mice for 8weeks on the anxiety like behavior and the underlying molecular mechanism. Elevated plus maze and open field test revealed that social isolation caused anxiety like behavior. BDNF, a well-known molecule implicated in the anxiety like behavior, was up-regulated both at the message and protein level in cerebral cortex by social isolation. CREB-1 and CBP, which play a crucial role in BDNF transcription, were up-regulated at mRNA level in cerebral cortex by social isolation. HDAC-2, which negatively regulates BDNF expression, was down-regulated at mRNA and protein level in cerebral cortex by social isolation. Furthermore, BDNF acts in concert with Limk-1, miRNA-132 and miRNA-134 for the regulation of structural and morphological plasticity. Social isolation resulted in up-regulation of Limk-1 mRNA and miRNA-132 expression in the cerebral cortex. MiRNA-134, which inhibits the translation of Limk-1, was decreased in cerebral cortex by social isolation. Taken together, our study suggests that social isolation mediated anxiety like behavior is associated with up-regulation of BDNF expression and concomitant increase in the expression of CBP, CREB-1, Limk-1 and miRNA-132, and decrease

  1. Dipole defects in beryl

    International Nuclear Information System (INIS)

    Holanda, B A; Cordeiro, R C; Blak, A R

    2010-01-01

    Dipole defects in gamma irradiated and thermally treated beryl (Be 3 Al 2 Si 6 O 18 ) samples have been studied using the Thermally Stimulated Depolarization Currents (TSDC) technique. TSDC experiments were performed in pink (morganite), green (emerald), blue (aquamarine) and colourless (goshenite) natural beryl. TSDC spectra present dipole peaks at 190K, 220K, 280K and 310K that change after gamma irradiation and thermal treatments. In morganite samples, for thermal treatments between 700K and 1100K, the 280K peak increase in intensity and the band at 220K disappears. An increase of the 280K peak and a decrease of the 190K peak were observed in the TSDC spectra of morganite after a gamma irradiation of 25kGy performed after the thermal treatments. In the case of emerald samples, thermal treatments enhanced the 280K peak and gamma irradiation partially destroyed this band. The goshenite TSDC spectra present only one band at 280K that is not affected either by thermal treatments or by gamma irradiation. All the observed peaks are of dipolar origin because the intensity of the bands is linearly dependent on the polarization field, behaviour of dipole defects. The systematic study, by means of TSDC measurements, of ionizing irradiation effects and thermal treatments in these crystals makes possible a better understanding of the role played by the impurities in beryl crystals.

  2. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence.

    Science.gov (United States)

    Xu, R; Duan, S R; Zhao, J W; Wang, C Y

    2015-08-01

    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.

  4. Electroconvulsive therapy (ECT) and aerobic exercise training (AET) increased plasma BDNF and ameliorated depressive symptoms in patients suffering from major depressive disorder.

    Science.gov (United States)

    Salehi, Iraj; Hosseini, Seyed Mohammad; Haghighi, Mohammad; Jahangard, Leila; Bajoghli, Hafez; Gerber, Markus; Pühse, Uwe; Holsboer-Trachsler, Edith; Brand, Serge

    2016-05-01

    To treat patients suffering from major depressive disorder (MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. plasma BDNF (pBDNF). 60 patients with MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 45 min, three times a week. Both depression severity and pBDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication. pBDNF levels increased over time in all three study conditions, though, highest increase was observed in the ECT + EAT condition, and lowest increase was observed in the AET condition. Depressive symptoms decreased in all three conditions over time, though, strongest decrease was observed in the ECT + AET condition. The combination of ECT + AET led to significantly greater remission rates than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression. The pattern of results suggests that ECT, AET and particularly their combination are promising directions for the treatment of patients suffering from MDD, and that it remains unclear to what extent pBDNF is key and a reliable biomarker for MDD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Impact of variation in the BDNF gene on social stress sensitivity and the buffering impact of positive emotions: replication and extension of a gene-environment interaction.

    Science.gov (United States)

    van Winkel, Mark; Peeters, Frenk; van Winkel, Ruud; Kenis, Gunter; Collip, Dina; Geschwind, Nicole; Jacobs, Nele; Derom, Catherine; Thiery, Evert; van Os, Jim; Myin-Germeys, Inez; Wichers, Marieke

    2014-06-01

    A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factor(Val66Met) (BDNF rs6265) genotype. Additionally, positive emotions partially neutralize this moderating effect. The current study aimed to: (i) replicate in a new independent sample of subjects with residual depressive symptoms the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity, (ii) replicate the neutralizing impact of positive emotions, (iii) extend these analyses to other variations in the BDNF gene in the new independent sample and the original sample of non-depressed individuals. Previous findings were replicated in an experience sampling method (ESM) study. Negative Affect (NA) responses to social stress were stronger in "Val/Met" carriers of BDNF(Val66Met) compared to "Val/Val" carriers. Positive emotions neutralized the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity in a dose-response fashion. Finally, two of four additional BDNF SNPs (rs11030101, rs2049046) showed similar moderating effects on social stress-sensitivity across both samples. The neutralizing effect of positive emotions on the moderating effects of these two additional SNPs was found in one sample. In conclusion, ESM has important advantages in gene-environment (GxE) research and may attribute to more consistent findings in future GxE research. This study shows how the impact of BDNF genetic variation on depressive symptoms may be explained by its impact on subtle daily life responses to social stress. Further, it shows that the generation of positive affect (PA) can buffer social stress sensitivity and partially undo the genetic susceptibility. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  6. 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.

  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)

    Xu, R.; Duan, S.R.; Zhao, J.W.; Wang, C.Y.

    2015-01-01

    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. BDNF Val66Met Polymorphism Influences Visuomotor Associative Learning and the Sensitivity to Action Observation

    Science.gov (United States)

    Taschereau-Dumouchel, Vincent; Hétu, Sébastien; Michon, Pierre-Emmanuel; Vachon-Presseau, Etienne; Massicotte, Elsa; De Beaumont, Louis; Fecteau, Shirley; Poirier, Judes; Mercier, Catherine; Chagnon, Yvon C.; Jackson, Philip L.

    2016-01-01

    Motor representations in the human mirror neuron system are tuned to respond to specific observed actions. This ability is widely believed to be influenced by genetic factors, but no study has reported a genetic variant affecting this system so far. One possibility is that genetic variants might interact with visuomotor associative learning to configure the system to respond to novel observed actions. In this perspective, we conducted a candidate gene study on the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, a genetic variant linked to motor learning in regions of the mirror neuron system, and tested the effect of this polymorphism on motor facilitation and visuomotor associative learning. In a single-pulse TMS study carried on 16 Met (Val/Met and Met/Met) and 16 Val/Val participants selected from a large pool of healthy volunteers, Met participants showed significantly less muscle-specific corticospinal sensitivity during action observation, as well as reduced visuomotor associative learning, compared to Val homozygotes. These results are the first evidence of a genetic variant tuning sensitivity to action observation and bring to light the importance of considering the intricate relation between genetics and associative learning in order to further understand the origin and function of the human mirror neuron system. PMID:27703276

  9. Neither cortisol nor brain-derived neurotrophic factor is associated with serotonin transporter in bipolar disorder.

    Science.gov (United States)

    Chou, Yuan-Hwa; Lirng, Jiing-Feng; Hsieh, Wen-Chi; Chiu, Yen-Chen; Tu, Yi-An; Wang, Shyh-Jen

    2016-02-01

    Converging evidence indicates the hypothalamus-pituitary-adrenal axis and serotonergic neurons exert reciprocal modulatory actions. Likewise, brain-derived neurotrophic factor (BDNF) has been implicated as a growth and differentiation factor in the development of serotonergic neurons. The aim of this study was to examine the interaction of cortisol and BDNF on serotonin transporter (SERT) in bipolar disorder (BD). Twenty-eight BD and 28 age- and gender-matched healthy controls (HCs) were recruited. (123)I-ADAM with single-photon emission computed tomography (SPECT) was applied for measurement of SERT availability in the brain, which included the midbrain, thalamus, putamen and caudate. Ten milliliters of venous blood was withdrawn, when the subject underwent SPECT, for the measurement of the plasma concentration of cortisol and BDNF. SERT availability was significantly decreased in the midbrain and caudate of BD compared with HCs, whereas plasma concentration of cortisol and BDNF did not show a significant difference. The linear mixed-effect model revealed that there was a significant interaction of group and cortisol on SERT availability of the midbrain, but not BDNF. Linear regression analyses by groups revealed that cortisol was associated with SERT availability in the midbrain in the HCs, but not in BD. Considering previous studies, which showed a significant association of cortisol with SERT availability in the HCs and major depressive disorder (MDD), our result replicated a similar finding in HCs. However, the negative finding of the association of cortisol and SERT availability in BD, which was different from MDD, suggests a different role for cortisol in the pathophysiology of mood disorder. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  10. Topological defects in extended inflation

    International Nuclear Information System (INIS)

    Copeland, E.J.; Kolb, E.W.; Chicago Univ., IL; Liddle, A.R.

    1990-04-01

    We consider the production of topological defects, especially cosmic strings, in extended inflation models. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of bubbles when they collide. This mechanism allows a natural combination of inflation and large-scale structure via cosmic strings. 18 refs

  11. Diaphragmatic defect in trisomy 13

    International Nuclear Information System (INIS)

    Reinbold, W.D.; Reinwein, H.; Back, E.

    1986-01-01

    Congenital diaphragmatic defect is often combined with other malformations that are severe or fatal. The rare finding of a congenital diaphragmatic defect in a newborn with trisomy 13 is reported. The newborn died within 2 days. Postmortem examination showed typical malformations due to trisomy 13 besides a diaphragmatic defect of left retrosternal position. Karyotype revealed a 13/14 translocation of trisomy 13. (orig.) [de

  12. Topological defects in extended inflation

    International Nuclear Information System (INIS)

    Copeland, E.J.; Kolb, E.W.; Liddle, A.R.

    1990-01-01

    We consider the production of topological defects, especially cosmic strings, in extended-inflation models. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of the bubbles when they collide. This mechanism allows a natural combination of inflation and large-scale structure via cosmic strings

  13. Dual-probe spectroscopic fingerprints of defects in graphene

    DEFF Research Database (Denmark)

    Settnes, Mikkel; Power, Stephen; Petersen, Dirch Hjorth

    2014-01-01

    (e.g., an extended graphene sheet). Applying this method, we study the transport anisotropies in pristine graphene sheets, and analyze the spectroscopic fingerprints arising from quantum interference around single-site defects, such as vacancies and adatoms. Furthermore, we demonstrate that the dual...

  14. Who named the quantum defect?

    Energy Technology Data Exchange (ETDEWEB)

    Rau, A.R.P. [Louisiana State Univ., Baton Rouge, LA (United States). Dept. of Physics and Astronomy; Inokuti, M. [Argonne National Lab., IL (United States). Physics Div.

    1997-08-01

    The notion of the quantum defect is important in atomic and molecular spectroscopy and also in unifying spectroscopy with collision theory. In the latter context, the quantum defect may be viewed as an ancestor of the phase shift. However, the origin of the term quantum defect does not seem to be explained in standard textbooks. It occurred in a 1921 paper by Schroedinger, preceding quantum mechanics, yet giving the correct meaning as an index of the short-range interactions with the core of an atom. The authors present the early history of the quantum-defect idea, and sketch its recent developments.

  15. Abnormalities in the zinc-metalloprotease-BDNF axis may contribute to megalencephaly and cortical hyperconnectivity in young autism spectrum disorder patients.

    Science.gov (United States)

    Koh, Jae-Young; Lim, Joon Seo; Byun, Hyae-Ran; Yoo, Min-Heui

    2014-09-03

    Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo- or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu. Consistently, some ASD patients, as well as some animal models of ASD, show increased levels of brain-derived neurotrophic factor (BDNF). However, how BDNF is upregulated in ASD is unknown. To address this question, we propose the novel hypothesis that a putative zinc-metalloprotease-BDNF (ZMB) axis in the forebrain plays a pivotal role in the development of hyperconnectivity and megalencephaly in ASD. We have previously demonstrated that extracellular zinc at micromolar concentrations can rapidly increase BDNF levels and phosphorylate the receptor tyrosine kinase TrkB via the activation of metalloproteases. The role of metalloproteases in ASD is still uncertain, but in fragile X syndrome, a monogenic disease with an autistic phenotype, the levels of MMP are increased. Early exposure to lipopolysaccharides (LPS) and other MMP activators such as organic mercurials also have been implicated in ASD pathogenesis. The resultant increases in BDNF levels at synapses, especially those involved in the zinc-containing, associative glutamatergic system may produce abnormal brain circuit development. Various genetic mutations that lead to ASD are also known to affect BDNF signaling: some down-regulate, and others up-regulate it. We hypothesize that, although both up- and down-regulation of BDNF may induce autism symptoms, only BDNF up-regulation is associated with the hyperconnectivity and large brain size observed in most young idiopathic ASD patients. To test this hypothesis, we propose to examine the

  16. Investigation of brain-derived neurotrophic factor (BDNF) gene expression in hypothalamus of obese rats: Modulation by omega-3 fatty acids.

    Science.gov (United States)

    Abdel-Maksoud, Sahar M; Hassanein, Sally I; Gohar, Neveen A; Attia, Saad M M; Gad, Mohamed Z

    2017-10-01

    The aim of this study was investigating the effect of omega-3 fatty acids (ω-3 FAs) on brain-derived neurotrophic factor (BDNF) gene expression, using in vivo and in vitro models, to unravel the potential mechanisms of polyunsaturated fatty acids use in obesity. Twenty-nine Sprague-Dawley rats were divided into three groups; lean controls fed normal chow diet for 14 weeks, obese controls fed 60% of their diet as saturated fats for 14 weeks, and ω-3 FAs-treated rats fed 60% saturated fat diet for 14 weeks with concomitant oral administration of 400 mg/kg/day ω-3 FAs, mainly docosahexaenoic acid and EPA, from week 12 to week 14. For the in vitro experiment, hypothalamic cells from six obese rats were cultured in the presence of different concentrations of ω-3 FAs to determine its direct effect on BDNF expression. In vivo results showed that obesity has negative effect on BDNF gene expression in rat hypothalamus that was reversed by administration of ω-3 FAs. Obese rats showed hypercholesterolemia, hypertriglyceridemia, normoinsulinemia, hyperglycemia and hyperleptinemia. Treatment with ω-3 FAs showed significant decrease in serum total cholesterol and TAG. Also serum glucose level and HOMA index were decreased significantly. In vitro results demonstrated the increase in BDNF expression by ω-3 FAs in a dose-dependent manner. Obesity causes down-regulation of BDNF gene expression that can be reversed by ω-3 FAs treatment, making them an interesting treatment approach for obesity and metabolic disease.

  17. Dose-Dependent Protective Effect of Lithium Chloride on Retinal Ganglion Cells Is Interrelated with an Upregulated Intraretinal BDNF after Optic Nerve Transection in Adult Rats

    Directory of Open Access Journals (Sweden)

    Ming-Mei Wu

    2014-08-01

    Full Text Available Neuroprotection of lithium for axotomized retinal ganglion cells (RGCs is attributed to upregulated intraretinal Bcl-2. As lithium also upregulates brain-derived neurotrophic factor (BDNF which can rescue axotomized RGCs, it is hypothesized that lithium could protect RGCs through BDNF. This study investigated this hypothesis and a possible relationship between the dose and protection of lithium. All adult experimental rats received daily intraperitoneal injections of lithium chloride (LiCl at 30, 60 or 85 mg/kg·bw until they were euthanized 2, 7 or 14 days after left intraorbital optic nerve (ON transection. Our results revealed that RGC densities promoted and declined with increased dose of LiCl and the highest RGC densities were always in the 60 mg/kg·bw LiCl group at both 7 and 14 day points. Similar promotion and decline in the mRNA and protein levels of intraretinal BDNF were also found at the 14 day point, while such BDNF levels increased in the 30 mg/kg·bw LiCl group but peaked in the 60 and 85 mg/kg·bw LiCl groups at the 7 day point. These findings suggested that lithium can delay the death of axotomized RGCs in a dose-dependent manner within a certain period after ON injury and such beneficial effect is interrelated with an upregulated level of intraretinal BDNF.

  18. 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

  19. Effects of aquatic exercise and CES treatment on the changes of cognitive function, BDNF, IGF-1, and VEGF of persons with intellectual disabilities.

    Science.gov (United States)

    Lee, In Ho; Seo, Eun Jung; Lim, In Soo

    2014-03-01

    The purpose of this study was to investigate the effects of aquatic exercise and CES treatment on the cognitive function by using K-WAB and BDNF, IGF-1, and VEGF of persons with intellectual disabilities. All subjects were 15 male with intellectual disabilities who were participating in the aquatic training program and CES treatment during 12 weeks at rehabilitation center. The subjects were divided into control group, exercise group, and exercise+CES group. Blood samples for BDNF, IGF-1, and VEGF were taken from brachial vein at rest between before and after treatment. The results are summarized as follows: Cognitive function level increased significantly in the exercise+CES group compared to those in the exercise and control group. The changes of blood IGF-1 concentration were no significant difference among groups. The changes of blood BDNF and VEGF concentration were significantly increased in exercise group and exercise+CES group than control group. However, blood BDNF and VEGF concentration were significantly difference between exercise group and exercise+CES group. In conclusion, it can be concluded that CES treatment with exercise can amend cognitive function of persons with intellectual disabilities more effectively and increase of BDNF and VEGF by exercise can explain the cognitive function improvement of persons with intellectual disabilities.

  20. Studies of defects and defect agglomerates by positron annihilation spectroscopy

    DEFF Research Database (Denmark)

    Eldrup, Morten Mostgaard; Singh, B.N.

    1997-01-01

    A brief introduction to positron annihilation spectroscopy (PAS), and in particular lo its use for defect studies in metals is given. Positrons injected into a metal may become trapped in defects such as vacancies, vacancy clusters, voids, bubbles and dislocations and subsequently annihilate from...

  1. Effect of charged line defects on conductivity in graphene: Numerical Kubo and analytical Boltzmann approaches

    DEFF Research Database (Denmark)

    Radchenko, T. M.; Shylau, A. A.; Zozoulenko, I. V.

    2013-01-01

    Charge carrier transport in single-layer graphene with one-dimensional charged defects is studied theoretically. Extended charged defects, considered an important factor for mobility degradation in chemically vapor-deposited graphene, are described by a self-consistent Thomas-Fermi potential...

  2. Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis

    NARCIS (Netherlands)

    Rachel, R.A.; May-Simera, H.L.; Veleri, S.; Gotoh, N.; Choi, B.Y.; Murga-Zamalloa, C.; McIntyre, J.C.; Marek, J.; Lopez, I.; Hackett, A.N.; Zhang, J.; Brooks, M.; Hollander, A.I. den; Beales, P.L.; Li, T.; Jacobson, S.G.; Sood, R.; Martens, J.R.; Liu, P.; Friedman, T.B.; Khanna, H.; Koenekoop, R.K.; Kelley, M.W.; Swaroop, A.

    2012-01-01

    Cilia are highly specialized microtubule-based organelles that have pivotal roles in numerous biological processes, including transducing sensory signals. Defects in cilia biogenesis and transport cause pleiotropic human ciliopathies. Mutations in over 30 different genes can lead to cilia defects,

  3. 49 CFR 215.109 - Defective plain bearing box: Journal lubrication system.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Defective plain bearing box: Journal lubrication... Freight Car Components Suspension System § 215.109 Defective plain bearing box: Journal lubrication system...) Metal parts contacting the journal; or (e) Is— (1) Missing; or (2) Not in contact with the journal. ...

  4. Birth defects surveillance in China.

    Science.gov (United States)

    Dai, Li; Zhu, Jun; Liang, Juan; Wang, Yan-Ping; Wang, He; Mao, Meng

    2011-11-01

    Birth defects are a global public health problem because of their large contribution to infant mortalities and disabilities. It is estimated that 4%-6% of Chinese newborns are affected by birth defects every year. Surveillance is a basic