PMC:3643078 / 8052-10042
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3643078","sourcedb":"PMC","sourceid":"3643078","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3643078","text":"Neural mediators of resilience\nWhile cortisol is an important allostatic mediator, other factors are surely involved. For instance, neurotrophins such as brain derived neurotrophic factor (BDNF) play a key role [11]. It has been demonstrated that chronic stress can decrease BDNF expression in the brain [12,13], though this relationship is a complex one [14,15] with reciprocal cross-talk between glucocorticoids and BDNF signaling. However, recently, a common polymorphism in the BDNF gene has been identified in humans, in which there is substitution of a valine at codon 66 with a methionine (val66met). Individuals who carry this mutation demonstrate reduced performance in hippocampal-dependent memory tasks and increased anxiety. The val66met mouse was developed using a transgenic approach. The mice have decreased BDNF secretion, a reduction in hippocampal volume, and changes in cognition [16,17], as well as increased anxiety levels [18,19]. In these models, alterations in BDNF signaling can be considered “risk factors” in the development of neuropsychiatric disease [20,21].\nOther studies have suggested an additional interpretation, in which BDNF is a necessary factor in the ability of the brain to show plasticity. For example, BDNF haploinsufficient mice show shrunken dendrites in the CA3 region of the hippocampus. However, these mice do not show further shrinkage of hippocampal dendrites when chronically stressed in contrast to WT mice, which do show stress-induced shrinkage [22]. The mechanisms by which BDNF plays these somewhat contradictory roles could be explained by a necessity for BDNF in plasticity in general, from neurite outgrowth and spine remodeling, to destabilization of existing spines [23,24]. Thus, trophic factors such as BDNF are facilitators of plasticity, and the outcome may be negative (e.g. epilepsy [25]) or positive (e.g. recovery from depression [26]) depending on the complex, perhaps hermetic, processes that are operating at the 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