Chronic psychosocial stress regulates the expression of both GR and MR mRNA in the hippocampal formation of tree shrews

Abstract

A persistent hyperactivity of the hypothalamic-pituitary-adrenal axis and thus elevated glucocorticoid levels are main neuroendocrine features of depressive symptomatology in humans. The broad range of effects that are set off by glucocorticoids is mediated by glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs), which themselves are subject to autoregulation. In order to investigate the impact of long-lasting psychological stress on corticosteroid receptor mRNA expression in the hippocampal formation, we employed the psychosocial stress paradigm in male tree shrews (Tupaia belangeri). By in situ hybridization studies and semiquantitative evaluation of stress-induced changes of GR and MR mRNA expression at the single-cell level, brain tissue from subordinate animals which were exposed to 27 days (1 h/day) of social confrontation was compared to that of nonstressed animals. Four weeks of stress exposure resulted in a downregulation of GR mRNA in the dentate gyrus and hippocampal subfields CA1 and CA3 of subordinate male tree shrews compared to controls. The MR mRNA content in these subfields of the anterior hippocampus was also clearly reduced. On the contrary, in a more posterior location on the longitudinal axis of the tree shrew hippocampus, the MR message was increased in subfields CA1 and CA3 and in the dentate gyrus. These results suggest a relevance of the stress-induced regulation of both corticosteroid receptor subtype mRNAs in a naturalistic challenging situation. Moreover, the differential regulation of MR mRNA along the rostrocaudal axis of the hippocampus adds another feature to the heterogenous composition of this structure.