Age-related differences in glucocorticoid receptor mRNA levels in the human brain.
Glucocorticoids and their receptors (GRs) are implicated in dynamic cognitive and neuroendocrine processes mediated by the prefrontal cortex and hippocampus. Additionally, a primary defect in forebrain GR levels can mimic symptoms of depression. We hypothesized that changes in GR mRNA levels may occur in the human brain across the life span thus positioning GR to differentially influence behavior and disease susceptibility. Following in situ hybridization with a riboprobe for human GR mRNA, we employed quantitative film autoradiography to measure expression levels in the prefrontal cortex and hippocampus in five age groups (infants, adolescents, young adults, adults, and aged) and in primary visual and visual association cortices for comparison. We detected a main effect of age group on cortical, but not hippocampal GR mRNA, with greater cortical expression in adolescents and adults than in infants or the aged. Increased GR mRNA in prefrontal cortex during adolescence and adulthood suggests that human GR-mediated forebrain regulation of cognition and the neuroendocrine stress response may be more salient during late maturation and at maturity.
MiNDS Unit, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892-1385, USA. perlmanw@intra.nimh.nih.gov
William R
WR
Perlman
Maree J
MJ
Webster
Mary M
MM
Herman
Joel E
JE
Kleinman
Cynthia Shannon
CS
Weickert
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D007223:Infant; D008297:Male; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism*
D011965:Receptors, Glucocorticoid