Regulation of Neurogenesis by Neurotrophins during Adulthood: Expected and Unexpected Roles.

Marçal Vilar,Helena Mira

doi:10.3389/fnins.2016.00026

Abstract

The subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus are the two main regions of the adult mammalian brain in which neurogenesis is maintained throughout life. Because alterations in adult neurogenesis appear to be a common hallmark of different neurodegenerative diseases, understanding the molecular mechanisms controlling adult neurogenesis is a focus of active research. Neurotrophic factors are a family of molecules that play critical roles in the survival and differentiation of neurons during development and in the control of neural plasticity in the adult. Several neurotrophins and neurotrophin receptors have been implicated in the regulation of adult neurogenesis at different levels. Here, we review the current understanding of neurotrophin modulation of adult neurogenesis in both the SVZ and SGZ. We compile data supporting a variety of roles for neurotrophins/neurotrophin receptors in different scenarios, including both expected and unexpected functions.

Highlights

Neurotrophins (NTs) are implicated in the maintenance and survival of the peripheral and central nervous systems and mediate several forms of synaptic plasticity (Chao, 2003; Ceni et al, 2014; Hempstead, 2014; Lu et al, 2014)
NTs interact with two distinct receptors, a cognate member of the Tropomyosin receptor kinase (Trk) receptor tyrosine kinase family and the common p75 neurotrophin receptor (p75NTR), which belongs to the tumor necrosis factor receptor (TNFR) superfamily of death receptors (Friedman and Greene, 1999; Huang and Reichardt, 2003)
In rats a larger proportion of subventricular zone (SVZ) cells express p75NTR, this receptor does not significantly co-localize with type B markers such as GFAP and appears to be largely confined to EGFR+ type C progenitor cells, with some low level expression in PSA-NCAM+ or DCX+ neuroblasts (Giuliani et al, 2004; Young et al, 2007). This suggests that p75NTR may play a greater role in the regulation of SVZ progenitor proliferation in rats than in mice, and that neurotrophin signaling in the two species may differ slightly

Summary

INTRODUCTION

Neurotrophins (NTs) are implicated in the maintenance and survival of the peripheral and central nervous systems and mediate several forms of synaptic plasticity (Chao, 2003; Ceni et al, 2014; Hempstead, 2014; Lu et al, 2014). Neurotrophins were first identified as survival factors for developing neurons, but are pleiotropic molecules that can exert a variety of functions, including the regulation of neuronal differentiation, axonal and dendritic growth, and synaptic plasticity (Bothwell, 2014). NGF is the preferred ligand for TrkA, BDNF, and NT4/5 are preferred for TrkB, and NT3 for TrkC. In addition to full length (FL) receptors, splice variants containing either deletions in the extracellular domain or intracellular truncations including the kinase domain have been described. These receptor molecules may influence ligand specificity, restrict its availability by internalization, or act as dominant-negative modulators. Splice variants of TrkB, designated T1 and T2, are expressed at high levels in the mature brain (Klein et al, 1990)

Regulation of Adult Neurogenesis by Neurotrophins

FUNCTIONAL SIGNIFICANCE OF NEUROTROPHINS AND THEIR RECEPTORS IN THE SVZ

FUNCTIONAL SIGNIFICANCE OF NEUROTROPHINS AND THEIR RECEPTORS IN THE SGZ

CONCLUDING REMARKS