Postnatal ontogeny of hippocampal expression of the mineralocorticoid and glucocorticoid receptors in the common marmoset monkey

Abstract

The mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are nuclear transcription factors that mediate many of the basal and stress functions and effects of the corticosteroid hormones, including those related to brain development. Despite this, relatively little is known about the postnatal ontogeny of MR and GR gene and protein expression in the central nervous system, and this is particularly true of the primates, including humans. Here we describe the postnatal ontogeny of central MR and GR gene and protein expression in the common marmoset monkey. By developing marmoset-specific riboprobes and using in situ hybridization, it was demonstrated that MR mRNA expression in the dentate gyrus and Ammon's horn was significantly greater in marmoset infants (aged 4-6 weeks) than in neonates (1-2 days), juveniles (4-5 months) and adults (3-6 years), with expression in the latter three ontogenetic stages being broadly similar. In the same subjects and ontogenetic stages, GR mRNA expression was developmentally consistent in the marmoset dentate gyrus and Ammon's horn, as well as in the paraventricular nucleus of the hypothalamus. Qualitative immunohistochemical comparison of infants and adults demonstrated that MR protein expression in the hippocampus was, as for mRNA, also greater in infants than adults, and that hippocampal GR protein was, as for mRNA, also similar in infants and adults. The increase in MR mRNA expression between the stages of neonate and infant co-occurred with a reduction in basal plasma ACTH and cortisol titres. The ontogenetic profiles of MR and GR gene expression in the marmoset monkey are therefore fundamentally different from those described for the rat and the mouse. This evidence for the postnatal ontogeny of central corticosteroid nuclear receptor expression in a primate is important for understanding both the developmental stage-specific significance of stress exposure and its potential long-term effects on health and disease.

Plasma Cortisol and Progression of Dementia in Subjects With Alzheimer-Type Dementia

“…This association is consistent with previous reports of relationships between increased HPA axis activity and age-related hippocampal volume loss (5). There have been conflicting reports about the density of GC receptor expression in the hippocampus relative to other regions of the primate brain (41,42,43). Nonetheless, our findings raise the intriguing possibility that increased GC levels may have a disproportionate impact on the AD disease process as it develops in the hippocampus and other structures of the medial temporal lobe (e.g., entorhinal cortex) (44).…”

Glucocorticoid Hormones Decrease Proliferation of Embryonic Neural Stem Cells through Ubiquitin-Mediated Degradation of Cyclin D1

“…The ontogeny of the GR has been studied in rodent and recently also in marmoset monkey brain tissue (Van Eekelen et al, 1991;Schmidt et al, 2003;Pryce et al, 2005). Previous studies on rat hippocampus showed that prenatal stress reduced neurogenesis and caused an impairment of hippocampal-dependent spatial learning as observed later in life (Lemaire et al, 2000).…”

Age-related accumulation of Reelin in amyloid-like deposits

“…Confirmation of the genotypes was done with postmortem tail biopsies as described (Oddo et al, 2003). Groups 5/6: The housing conditions for rats and common marmoset monkeys were as described (Nyffeler et al, 2007;Pryce et al, 2005).…”

“…Louis, MO) staining for 5 -10 min as described Nyffeler et al, 2007;Pryce et al, 2005). Counterstaining of Reelin-IP labeling was done with 0.25% Cresyl violet according to standard protocols.…”