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Publication : Variant brain-derived neurotrophic factor (Valine66Methionine) polymorphism contributes to developmental and estrous stage-specific expression of anxiety-like behavior in female mice.

First Author  Bath KG Year  2012
Journal  Biol Psychiatry Volume  72
Issue  6 Pages  499-504
PubMed ID  22552045 Mgi Jnum  J:283148
Mgi Id  MGI:6378067 Doi  10.1016/j.biopsych.2012.03.032
Citation  Bath KG, et al. (2012) Variant brain-derived neurotrophic factor (Valine66Methionine) polymorphism contributes to developmental and estrous stage-specific expression of anxiety-like behavior in female mice. Biol Psychiatry 72(6):499-504
abstractText  BACKGROUND: Most anxiety and depressive disorders are twice as common in women compared with men, and the sex difference in prevalence typically emerges during adolescence. Hormonal changes across the menstrual cycle and during the postpartum and perimenopausal periods are associated with increased risk for anxiety and depression symptoms. In humans and animals, reduced brain-derived neurotrophic factor (BDNF) has been associated with increased expression of affective pathology. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (BDNF Valine66Methionine [Val66Met]), which reduces BDNF bioavailability, has been identified in humans and associated with a variety of neuropsychiatric disorders. Although BDNF expression can be directly influenced by estrogen and progesterone, the potential impact of the BDNF Val66Met SNP on sensitivity to reproductive hormone changes remains an open question. METHODS: As a predictive model, we used female mice in which the human SNP (BDNF Val66Met) was inserted into the mouse BDNF gene. Using standard behavioral paradigms, we tested the impact of this SNP on age and estrous-cycle-specific expression of anxiety-like behaviors. RESULTS: Mice homozygous for the BDNF Val66Met SNP begin to exhibit increased anxiety-like behaviors over prepubertal and early adult development, show significant fluctuations in anxiety-like behaviors over the estrous cycle, and, as adults, differ from wild-type mice by showing significant fluctuations in anxiety-like behaviors over the estrous cycle-specifically, more anxiety-like behaviors during the estrus phase. CONCLUSIONS: These findings have implications regarding the potential role of this SNP in contributing to developmental and reproductive hormone-dependent changes in affective disorders in humans.
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