Intervention of Brain-Derived Neurotrophic Factor and Other Neurotrophins in Adult Neurogenesis.

Abstract

Cell survival during adult neurogenesis and the modulation of each step, namely, proliferation, lineage differentiation, migration, maturation, and functional integration of the newborn cells into the existing circuitry, is regulated by intrinsic and extrinsic factors. Transduction of extracellular niche signals triggers the activation of intracellular mechanisms that regulate adult neurogenesis by affecting gene expression. While the intrinsic factors include transcription factors and epigenetic regulators, the extrinsic factors are molecular signals that are present in the neurogenic niche microenvironment. These include morphogens, growth factors, neurotransmitters, and signaling molecules secreted as soluble factors or associated to the extracellular matrix. Among these molecular mechanisms are neurotrophins and neurotrophin receptors which have been implicated in the regulation of adult neurogenesis at different levels, with brain-derived neurotrophic factor (BDNF) being the most studied neurotrophin. In this chapter, we review the current knowledge about the role of neurotrophins in the regulation of adult neurogenesis in both the subventricular zone (SVZ) and the hippocampal subgranular zone (SGZ).