The role of BDNF in depression on the basis of its location in the neural circuitry

Abstract

Depression is one of the most prevalent and life-threatening forms of mental illnesses and the neural circuitry underlying depression remains incompletely understood. Most attention in the field has focused on hippocampal and frontal cortical regions for their roles in depression and antidepressant action. While these regions no doubt play important roles in the mental illness, there is compelling evidence that other brain regions are also involved. Brain-derived neurotrophic factor (BDNF) is broadly expressed in the developing and adult mammalian brain and has been implicated in development, neural regeneration, synaptic transmission, synaptic plasticity and neurogenesis. Recently BDNF has been shown to play an important role in the pathophysiology of depression, however there are controversial reports about the effects of BDNF on depression. Here, we present an overview of the current knowledge concerning BDNF actions and associated intracellular signaling in hippocampus, prefrontal cortex, nucleus accumbens (NAc) and amygdala as their relation to depression.

Bipolar disorder risk gene FOXO6 modulates negative symptoms in schizophrenia: a neuroimaging genetics study

“…The association between FOXO6 and the Akt/P13K signalling pathway is of particular interest owing to its downstream effects on cAMP response element binding protein and brain-derived neurotrophic factor 61 and prior associations with schizophrenia, 45 depression 62 and oxidative stress. 63 Additionally, many antipsychotic drugs increase phosphorylation of Akt as well as the associated GSK-3b, 45 whose phosphorylation is mediated by the Wnt signalling pathway, associated with negative symptom risk gene BCL9.…”

The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model

“…Rodent studies indicate that maternal behavior including postnatal maternal separation (negative) and higher quality maternal care (positive) can influence offspring's BDNF expression in brain (Bath et al 2013;Cutuli et al 2015;Mashoodh et al 2012). Noteworthy, too, is accumulating evidence of the diverse role of BDNF on depression in different brain regions (Yu and Chen 2011), such that in the hippocampus BNDF inhibits depression (Duman and Monteggia 2006) whereas in the nucleus accumbens (NAc) it facilitates depression (Groves 2007;Martinowich et al 2007). Collectively, these results provide the basis for the hypothesis that BDNF Val66Met and maternal parenting interactively influence abnormal BDNF levels in the brain and thus contribute to depressive symptoms.…”

Diferencias individuales en modelos animales: un enfoque para el estudio de factores neurobiológicos relacionados con depresión

“…Nuestros datos sugieren una dinámica distinta entre animales con alta y baja inmovilidad donde el efecto relacionado con la PNF (i.e., la reducción en la neurotrofina) se da con una cinética temporal distinta. Es importante mencionar una discrepancia con respecto a lo esperado; la disminución en los niveles de BDNF ha sido ampliamente asociada con el surgimiento de la depresión (Yu & Chen, 2011) y desde ese punto de vista, es de esperar que los animales "más deprimidos" experimenten una disminución mayor o al menos más rápida de esta neurotrofina.…”