Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior
Zhe-Yu Chen,Deqiang Jing,Kevin G. Bath,Alessandro Ieraci,Tanvir Khan,Chia-Jen Siao,Daniel G. Herrera,Miklós Tóth,Chingwen Yang,Bruce S. McEwen,Barbara L. Hempstead,Francis S. Lee +11 more
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TLDR
A variant BDNF mouse (BDNFMet/Met) is generated that reproduces the phenotypic hallmarks in humans with the variant allele and may play a key role in genetic predispositions to anxiety and depressive disorders.Abstract:
A common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNFMet/Met) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNFMet was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNFMet/Met mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.read more
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References
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene
Avshalom Caspi,Karen Sugden,Terrie E. Moffitt,Alan Taylor,Ian W. Craig,Hona Lee Harrington,Joseph L. McClay,Jonathan Mill,Judy Martin,Antony W. Braithwaite,Richie Poulton +10 more
TL;DR: Evidence of a gene-by-environment interaction is provided, in which an individual's response to environmental insults is moderated by his or her genetic makeup.
Journal ArticleDOI
Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants
Luca Santarelli,Michael Saxe,Cornelius Gross,Alexandre Surget,Fortunato Battaglia,Stephanie C. Dulawa,Noelia V. Weisstaub,James T. Lee,Ronald S. Duman,Ottavio Arancio,Catherine Belzung,René Hen +11 more
TL;DR: It is shown that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants, suggesting that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neuroGenesis in the hippocampus.
Journal ArticleDOI
The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function
Michael F. Egan,Masami Kojima,Masami Kojima,Joseph H. Callicott,Terry E. Goldberg,Bhaskar Kolachana,Alessandro Bertolino,Eugene Zaitsev,Bert Gold,David Goldman,Michael Dean,Bai Lu,Daniel R. Weinberger +12 more
TL;DR: A role is demonstrated for BDNF and its val/met polymorphism in human memory and hippocampal function and it is suggested val/ met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF.
Journal ArticleDOI
Regulation of BDNF and trkB mRNA in Rat Brain by Chronic Electroconvulsive Seizure and Antidepressant Drug Treatments
TL;DR: The enhanced induction and prolonged expression of BDNF in response to chronic ECS and antidepressant drug treatments could promote neuronal survival, and protect neurons from the damaging effects of stress.