The effect of adolescent testosterone on hippocampal BDNF and TrkB mRNA expression: relationship with cell proliferation.

Katherine M Allen,Cynthia Shannon Weickert,Tertia D Purves-Tyson,Samantha J Fung

doi:10.1186/s12868-015-0142-x

Katherine M Allen, Cynthia Shannon Weickert + Show 2 more

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https://doi.org/10.1186/s12868-015-0142-x

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Abstract

BackgroundTestosterone attenuates postnatal hippocampal neurogenesis in adolescent male rhesus macaques through altering neuronal survival. While brain-derived neurotropic factor (BDNF)/ tyrosine kinase receptor B (TrkB) are critical in regulating neuronal survival, it is not known if the molecular mechanism underlying testosterone’s action on postnatal neurogenesis involves changes in BDNF/TrkB levels. First, (1) we sought to localize the site of synthesis of the full length and truncated TrkB receptor in the neurogenic regions of the adolescent rhesus macaque hippocampus. Next, (2) we asked if gonadectomy or sex hormone replacement altered hippocampal BDNF and TrkB expression level in mammalian hippocampus (rhesus macaque and Sprague Dawley rat), and (3) if the relationship between BDNF/TrkB expression was altered depending on the sex steroid environment.ResultsWe find that truncated TrkB mRNA+ cells are highly abundant in the proliferative subgranular zone (SGZ) of the primate hippocampus; in addition, there are scant and scattered full length TrkB mRNA+ cells in this region. Gonadectomy or sex steroid replacement did not alter BDNF or TrkB mRNA levels in young adult male rat or rhesus macaque hippocampus. In the monkey and rat, we find a positive correlation with cell proliferation and TrkB-TK+ mRNA expression, and this positive relationship was found only when sex steroids were present.ConclusionsWe suggest that testosterone does not down-regulate neurogenesis at adolescence via overall changes in BDNF or TrkB expression. However, BDNF/TrkB mRNA appears to have a greater link to cell proliferation in the presence of circulating testosterone.

Highlights

Testosterone attenuates postnatal hippocampal neurogenesis in adolescent male rhesus macaques through altering neuronal survival
tyrosine kinase receptor B (TrkB)-tyrosine kinase (TK)+ and TrkB-TK- mRNA expression in hippocampal subregions in the monkey As distinct TrkB isoforms appear to regulate different stages of neurogenesis [19], we investigated the presence of TrkB-TK+ and TrkB-TK- mRNA in the subgranular zone, granule cell layer and hilus in the rhesus macaque
In contrast to TrkBTK+, TrkB-TK- mRNA showed limited expression within the granule cell layer itself, there were numerous individual cells at the boundary of the granule cell and molecular layers which expressed TrkBTK- but these TK- expressing cells found superficial to the granule cell layer did not appear as densely packed as the TK-expressing cells found deep to the granule cell layer

Summary

Introduction

Testosterone attenuates postnatal hippocampal neurogenesis in adolescent male rhesus macaques through altering neuronal survival. (1) we sought to localize the site of synthesis of the full length and truncated TrkB receptor in the neurogenic regions of the adolescent rhesus macaque hippocampus. (2) we asked if gonadectomy or sex hormone replacement altered hippocampal BDNF and TrkB expression level in mammalian hippocampus (rhesus macaque and Sprague Dawley rat), and (3) if the relationship between BDNF/TrkB expression was altered depending on the sex steroid environment. Our study in adolescent male rhesus macaques found that gonadectomy increases nacent neuron survival and increases markers of immature neurons in the hippocampus [4], suggesting that testosterone may differentially modulate neurogenesis at adolescence. TrkB is found as a full length (TrkB-TK+) form that is capable of activating differentiation and survival

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