Ontogenetic Change in the Regional Distribution of Dehydroepiandrosterone-Synthesizing Enzyme and the Glucocorticoid Receptor in the Brain of the Spiny Mouse <b><i>(Acomys cahirinus)</i></b>

Abstract

The androgen dehydroepiandrosterone (DHEA) has trophic and anti-glucocorticoid actions on brain growth. The adrenal gland of the spiny mouse (Acomys cahirinus) synthesizes DHEA. The aim of this study was to determine whether the brain of this precocial species is also able to produce DHEA de novo during fetal, neonatal and adult life. The expression of P450c17 and cytochrome b5 (Cytb5), the enzyme and accessory protein responsible for the synthesis of DHEA, was determined in fetal, neonatal and adult brains by immunocytochemistry, and P450c17 bioactivity was determined by the conversion of pregnenolone to DHEA. Homogenates of fetal brain produced significantly more DHEA after 48 h in culture (22.46 ± 2.0 ng/mg tissue) than adult brain homogenates (5.04 ± 2.0 ng/mg tissue; p < 0.0001). P450c17 and Cytb5 were co-expressed in fetal neurons but predominantly in oligodendrocytes and white matter tracts in the adult brain. Because DHEA modulates glucocorticoids actions, the expression of the glucocorticoid receptor (GR) was also determined. In the brainstem, medulla, midbrain, and cerebellum, the predominant GR localization changed from neurons in the fetal brain to oligodendrocytes and white matter tracts in the adult brain. The change of expression of P450c17, Cytb5 and GR proteins with cell type, brain region and developmental age indicates that DHEA is an endogenous neurosteroid in this species that may have important trophic and stress-modifying actions during both prenatal and postnatal life.

Expression and glucocorticoid-dependent regulation of the stress-inducible protein DRR1 in the mouse adult brain

“…One possible explanation is that DRR1 mRNA could be strongly induced in oligodendrocytes, where DRR1 is lowly expressed under baseline conditions (Cahoy et al 2008 ), and/or a consequence of an increase in corticosteroid-induced oligodendrogenesis (Chetty et al 2014 ). In this line, glucocorticoid receptor expression is especially strong in white matter tracts in the adult mouse (Quinn et al 2016 ). Another possibility is that DRR1 mRNA is transported to the terminal, as for example the actin-regulating protein Arc (Huang et al 2007 ).…”

Central intracrine DHEA synthesis in ageing-related neuroinflammation and neurodegeneration: therapeutic potential?

“…It has also been shown in spiny mice that cortisol is the main glucocorticoid in the blood, unlike in rats where corticosterone is the main circulating glucocorticoid [ 160 , 161 ]. Most importantly, explanted foetal, neonate and adult spiny mouse brain tissue in culture have been shown capable of producing DHEA in the presence of pregnenolone [ 164 ]. In addition, spiny mouse also exhibit an age-related decline in DHEA synthesis [ 163 ].…”

De novo transcriptome assembly for the spiny mouse (Acomys cahirinus)

“…The Common or Cairo spiny mouse ( Acomys cahirinus ) is a small rodent species endemic to the semi-arid deserts of Africa and the Middle East 1 . Used in research to model human disease, spiny mice exhibit physiological characteristics not typically found in rodents: they exhibit a precocial pattern of development 2 , 3 , atypical synthesis of hormones such as cortisol and dehydroepiandosterone 4 – 6 , and a menstrual cycle 7 . These traits are common to humans and other higher order primates, but rare in other mammals.…”