title: Corticosterone alters N-methyl-D-aspartate receptor subunit mRNA expression before puberty.
abstract: Stress and stress hormones alter the expression of mRNA for the NR1, NR2A and NR2B subunits of the N-methyl-D-aspartate (NMDA) receptor in brain regions associated with the stress response. Early life stress contributes to the risk and pathophysiology of mental illness. Examining how stress hormones modulate NMDA receptor subunit gene expression before and after pubertal onset will further contribute to the understanding of how stress during adolescence relates to adult mental illness. Using in situ hybridization histochemistry, we measured NR1, NR2A and NR2B mRNA expression in the hippocampus and in the hypothalamic paraventricular nucleus (PVN) of rats that had undergone adrenalectomy (ADX) or sham surgery before or after puberty. Some ADX rats received corticosterone pellets that released either normal or stress levels of corticosterone for 14 days prior to sacrifice. There was a significant increase in NR1 subunit mRNA expression throughout the subfields of the hippocampus and in the PVN of ADX prepubertal rats. However, similar changes in hippocampal NR1 expression were not observed in postpubertal ADX rats. Pre- and postpubertal ADX rats implanted with a high-dose corticosterone pellet had decreased expression of PVN NR1 mRNA. Only prepubertal rats had an increase in dentate gyrus NR2A mRNA and CA3 region NR2B mRNA following high-dose replacement. These results provide evidence that glucocorticoids have differential effects on the regional expression of mRNA NMDA receptor subunits and elucidate a window during adolescence in which the NR1, NR2A and NR2B genes are responsive to glucocorticoids.
authors.affiliation: Program in Neuroscience, University of Maryland Baltimore, Baltimore, MD, USA. plee@mprc.umaryland.edu
authors.forename: Paul R
authors.initials: PR
authors.lastname: Lee
authors.forename: Dana
authors.initials: D
authors.lastname: Brady
authors.forename: James I
authors.initials: JI
authors.lastname: Koenig
mesh_terms: D000293:Adolescent / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D011627:Puberty / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*
chemical_list: C473649:NR1A NMDA receptor, rat; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D003345:Corticosterone