Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions.

Abstract

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in the central nervous system, promoting synaptic plasticity, neurogenesis and neuroprotection. The BDNF gene structure is very complex and consists of multiple 5'-non-coding exons, which give rise to differently spliced transcripts, and one coding exon at the 3'-end. These multiple transcripts, together with the complex transcriptional regulatory machinery, lead to a complex and fine regulation of BDNF expression that can be tissue and stimulus specific. BDNF effects are mainly mediated by the high-affinity, tropomyosin-related, kinase B receptor and involve the activation of several downstream cascades, including the mitogen-activated protein kinase, phospholipase C-γ and phosphoinositide-3-kinase pathways. BDNF exerts a wide range of effects on neuronal function, including the modulation of activity-dependent synaptic plasticity and neurogenesis. Importantly, alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response, which has important implications in psychiatric diseases, such as major depressive disorders and schizophrenia. In the present review, we have summarized the main features of BDNF in relation to neuronal plasticity, stress response and pathological conditions, and discussed the role of BDNF as a possible target for pharmacological and non-pharmacological treatments in the context of psychiatric illnesses.