BDNF function and intracellular signaling in neurons

Abstract

Brain-derived neurotrophic factor (BDNF)and its receptor, TrkB, are broadly expressed in thedeveloping and adult mammalian brain. BDNF/TrkB-stimulated intracellular signaling is critical for neuronalsurvival, morphogenesis, and plasticity. It is well knownthat binding of BDNF to TrkB elicits variousintracellular signaling pathways, including mitogen-activated protein kinase/extracellular signal-regulatedprotein kinase (MAPK/ERK), phospholipase Cγ(PLCγ),and phosphoinositide 3-kinase (PI3K) pathways, andthat BDNF exerts biological effects on neurons viaactivation of similar mechanisms. In addition to TrkB, alow-affinity receptor p75 is also involved in neuronalsurvival and plasticity. BDNF affects neurons positivelyor negatively through various intracellular signalingpathways triggered by activation of TrkB or p75. From aclinical standpoint, roles of BDNF have been implicatedin the pathophysiology of various brain diseases. Thestress-induced steroid hormone, glucocorticoid, andBDNF are putatively associated with thepathophysiology of depression. Recent reports, includingour studies, demonstrate possible crosstalk betweenglucocorticoid- and BDNF/TrkB-mediated signaling.Here, we present a broad overview of the currentknowledge concerning BDNF action and associatedintracellular signaling as it relates to neuronal protection,synaptic function, and morphological change.Furthermore, understanding the secretion andintracellular dynamics of BDNF proteins is critical as thefate of secreted BDNF may contribute to differences inneuronal response