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Keywords:

  • ageing;
  • neurogenesis;
  • neuroprotection;
  • StAR;
  • steroidogenesis

Abstract

The central nervous system synthesizes steroids which regulate the development and function of neurons and glia and have neuroprotective properties. The first step in this process involves the delivery of free cholesterol to the inner mitochondrial membrane where it can be converted into pregnenolone. This delivery is mediated by steroidogenic acute regulatory protein (StAR). Here, we present a detailed analysis of the distribution of StAR expression in neurons and glia, in the developing, adult and aged male rat brain. Immunohistochemical analysis revealed that StAR is widely distributed throughout the brain, although in each brain area it is restricted to very specific neuronal and astroglial populations. In most regions expressing StAR, immunoreactivity appeared at P10 and the levels of expression then either increased or remained constant until adulthood. In 2-year-old rat brains, StAR immunoreactivity was increased compared to young adults. StAR was expressed in the subventricular zone of the adult brain, in proliferating cells which incorporate BrdU as well as in germinal layers in the developing brain. These findings indicate that StAR expression is developmentally regulated and that StAR may play some function in regulating cell proliferation in the brain. Furthermore, StAR mRNA and protein levels were acutely and transiently increased in the hippocampus following excitotoxic brain injury induced by the administration of kainic acid. This raises the possibility that the up-regulation of StAR expression and the subsequent modifications in steroidogenesis may be part of the mechanisms used by the brain to cope with neurodegeneration.