期刊
CEREBRAL CORTEX
卷 30, 期 2, 页码 575-586出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhz108
关键词
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资金
- Heart and Stroke Foundation of Canada fund
- Canada Foundation for Innovation under Compute Canada
- Government of Ontario, Ontario Research Fund-Research Excellence
- University of Toronto
- German Federal State of Mecklenburg-West Pomerania
- Siemens Healthineers, Erlangen, Germany
- Federal State of Mecklenburg-West Pomerania
- German Centre of Neurodegenerative Diseases
- EU-JPND [FKZ: 01ED1615]
- Age UK (Disconnected Mind project)
- UK Medical Research Council (MRC) [G0701120, G1001245, MR/M013111/1]
- 16 NIH Institutes and Centers [1U54MH091657]
- McDonnell Center for Systems Neuroscience atWashington University
- Australian National Health and Medical Research Council Program Grant [ID1093083]
- Dementia Momentum
- National Health & Medical Research Council (NHMRC)
- Australian Research Council (ARC) Strategic Award Grant of the Ageing Well, Ageing Productively Program [401162]
- NHMRC [1045325, 1085606]
- NIH [P50AG00561, P30NS09857781, P01AG026276, P01AG003991, R01AG043434, UL1TR000448, R01EB009352]
- MRC [MR/R024065/1, MR/N027558/1, G1001245, MR/M013111/1, G0701120] Funding Source: UKRI
- National Health and Medical Research Council of Australia [1085606] Funding Source: NHMRC
Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n =21251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.
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