Role of p75 neurotrophin receptor in the development of neuronal and oligodendroglial progenitors of the rat postnatal subventricular zone
Creators: name: Joshi, Subhashini
Publisher: name: No Publisher Supplied
Year: 2022

description: The p75 neurotrophin receptor is widely expressed in the brain during embryonic development (Frade &amp; Barde, 1998). In neonatal and adult ages its expression in the central nervous system gets restricted to specific cell populations including cholinergic neurons of the basal forebrain, olfactory ensheathing glia, progenitors of the hippocampus and progenitors of the cerebellum where it plays a multitude of roles. While some studies have also reported that the subventricular zone (SVZ) expresses p75NTR in postnatal and adult stages (Galvão, RP, Garcea-Verdugo, JM, Alvarez-Buylla, 2008; Giuliani et al., 2004; van Strien et al., 2014; Young, Merson, et al., 2007), its exact role in this germinal niche remains unknown. Further, the expression of p75NTR has been reported at various ages in the rat and human SVZ but it is not observed in mice (Galvão, RP, Garcea-Verdugo, JM, Alvarez-Buylla, 2008). Although species differences remain unexplained, no comprehensive studies of p75NTR, regarding its role in the rat or human SVZ, have been conducted thus far. The SVZ serves as a neurogenic niche for the olfactory bulb in adult animals (Alvarez-Buylla et al., 2002; Bath &amp; Lee, 2010; Faigle &amp; Song, 2013). For a brief period postnatally, it also generates glial cells, predominantly oligodendrocytes for the corpus callosum, cortex and striatum (Kessaris et al., 2006.; Kuhn et al., 2019; Luskin &amp; McDermott, 1994; Menn et al., 2006; Naruse et al., 2017). Initial characterization showed expression of p75NTR in the dorsolateral SVZ throughout postnatal development in rats with maximal expression observed during the period of gliogenesis. Therefore, I hypothesized that p75NTR may be involved in the regulation of SVZ progenitor development during postnatal development.This study shows that p75NTR regulates both neuronal and oligodendroglial progenitors in the postnatal SVZ. Progenitors expressing p75NTR proliferate longer than cells in the dSVZ that lack p75NTR. I also determine that in the absence of p75NTR, postnatal oligodendrocyte progenitor development was accelerated in comparison to that observed under normal conditions. Consequently, I observed premature maturation of oligodendrocytes at postnatal ages which could have implications for myelination. Furthermore, I describe a role for p75NTR in neurogenesis where p75NTR defines a specific neuronal subpopulation expressing the transcription factor Pax6. I show that, postnatally, p75NTR is expressed by proliferating cells present in the rostral migratory stream extending from the lateral ventricle to the olfactory bulb. In younger animals, absence of p75NTR did not alter the cytoarchitecture of the olfactory bulb and did not affect odor discrimination. However, lack of p75NTR functionally affected odor discrimination in aged rats and led to changes in the olfactory bulb circuitry. Overall, this study defines a novel role for the multifunctional receptor p75NTR in the SVZ in regulation of oligodendrocyte progenitors in vivo during postnatal development. Further, I provide evidence that the role of p75NTR is not limited to a single subset of oligodendrocyte lineage committed progenitors but could have additional roles in olfactory bulb neurogenesis as a result of ageing.