PMC:3649690 / 24501-27275 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3649690","sourcedb":"PMC","sourceid":"3649690","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3649690","text":"11. Role of Neurotrophic Factors in Antidepressant Efficacy\nBrain-derived neurotrophic factor (BDNF) has been implicated in the etiology and treatment of depression. Depressed patients show decreased levels of serum BDNF [125, 126], which is correlated with decreased hippocampal volume and increased ratings of depression [126]. Conversely, increased BDNF levels are associated with antidepressant treatment and alleviation of depression [127]. These findings are mirrored in rodent models of depression [128–132] as chronic antidepressant treatment increases BDNF levels, coinciding with alleviation of depressive-like behaviours [130–132], and intracranial infusion of BDNF produces antidepressant effects [128, 133]. \nActivation of the TrkB neurotrophin receptor largely mediates the plasticity-enhancing actions of BDNF [134–136], where inhibition of TrkB signalling attenuates the behavioural efficacy of antidepressants [136]. Conversely BDNF, or more specifically proBDNF, via activation of the p75 neurotrophin receptor mediates plasticity-reducing actions such as apoptosis, neural atrophy, and synaptic pruning [137]. It has been postulated that the balance of TrkB and p75 signalling may underlie antidepressant effects of BDNF, suggesting a mechanism through which stress/depression may modulate the effects of BDNF. To this point, knocking out TrkB receptors fails to produce a depressive-like phenotype in neurogenesis-dependent or -independent behavioural measures of antidepressant efficacy [138, 139]; however sex differences exist as female TrkB knockouts do appear to develop a depressive-like behavioural phenotype [140]. \nInterestingly, PSA-NCAM interacts with BDNF, as removal of PSA from NCAM inhibits the induction of LTP, and the application of exogenous BDNF restores LTP at the affected synapse [141]. Further, disruption of the polysialylation of NCAM also disturbs the effects of BDNF on cortical neuron differentiation and survival, while the application of exogenous BDNF reverses these effects [142]. These findings suggest that PSA-NCAM may mediate the responsiveness of neurons to BDNF. It is known that PSA-NCAM interacts with, and may regulate, p75 expression in septal neurons [143] and newly generated neurons of the SVZ [144]. Indeed knockout of p75 significantly reduces the expression of PSA-NCAM in SVZ neuroblasts [145]. As previously mentioned the p75 receptor is involved in the regulation of adult hippocampal neurogenesis [146] and regulates neurogenesis stimulated by chronic antidepressant treatment [147]. Given the complex and varied role of BDNF in the etiology of depression and antidepressant treatment more research is needed to further elucidate a mechanism through which the modulation of BDNF exerts its 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