Neurotrophic factor control of adult SVZ neurogenesis

Abstract

Neurogenesis is the process by which cells divide, migrate, and subsequently differentiate into a neuronal phenotype. Significant rates of neurogenesis persist into adulthood in two brain regions, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles. Cells of the SVZ divide and migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB) where they differentiate into granule and periglomerular cells. With the discovery of large-scale neurogenesis in the adult brain, there have been significant efforts to identify the mechanisms that control this process as well as the role of these cells in neuronal functioning. Neurotrophic factors are a family of molecules that serve critical roles in the survival and differentiation of neurons during development, as well as contribute to continued plasticity throughout life. Several members of the neurotrophin family have been implicated in the control of adult postnatal SVZ neurogenesis. In this review we will address what is currently known regarding neurotrophic factor-dependent control of SVZ neurogenesis and place these findings in the context of what is known regarding other growth factors.

Figure 1

Developmental expression of BDNF, TrkB, and p75^NTR in mouse OB. Histograms depict relative levels of (a) BDNF, (b) TrkB, and (c) p75NTR mRNA in the olfactory bulb of mice at different developmental time points (n = 3 per group). All samples were run in triplicate and normalize to GAPDH.

Figure 2

Comparison of commercially available p75^NTR antibodies. Photomicrographs of p75^NTR immunoreactivity in brains of wild-type (WT) and p75^NTR-null (p75^NTR KO) mice. Comparisons were made between the c-terminal (c-term) and n-terminal (n-term) antibodies from Santa Cruz Biotechnology, (SC- Cat#'s sc6188 and sc6189 respectively) and a c-terminal antibody from R&D Systems (R&D- Cat# AF1157). Immunolabeling was carried out in adjacent sections from a single wild-type and a single p75^NTR null mouse. Immunoreactivity was compared in the basal forebrain (a, b, e, f, i, and j) and rostral migratory stream (RMS) (c, d, h, k, and l).