期刊
JOURNAL OF NEUROSCIENCE
卷 38, 期 9, 页码 2328-2340出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2568-17.2018
关键词
repeated social defeat; corticosterone; HPA axis; inflammation; monocytes
资金
- National Institute of Health [R01-MH-093473, R01-MH097243]
- National Institute of Aging [R01-AG033028]
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH097243, R01MH093473] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG033028] Funding Source: NIH RePORTER
Repeated social defeat (RSD) stress promotes the release of bone marrow-derived monocytes into circulation that are recruited to the brain, where they augment neuroinflammation and cause prolonged anxiety-like behavior. Physiological stress activates the sympathetic nervous system and hypothalamic-pituitary-adrenal gland (HPA) axis, and both of these systems play a role in the physiological, immunological, and behavioral responses to stress. The purpose of this study was to delineate the role of HPA activation and corticosterone production in the immunological responses to stress in male C57BL/6 mice. Here, surgical (adrenalectomy) and pharmacological (metyrapone) interventions were used to abrogate corticosterone signaling during stress. We report that both adrenalectomy and metyrapone attenuated the stress-induced release of monocytes into circulation. Neither intervention altered the production of monocytes during stress, but both interventions enhanced retention of these cells in the bone marrow. Consistent with this observation, adrenalectomy and metyrapone also prevented the stress-induced reduction of a key retention factor, CXCL12, in the bone marrow. Corticosterone depletion with metyrapone also abrogated the stress-induced glucocorticoid resistance of myeloid cells. In the brain, these corticosterone-associated interventions attenuated stress-induced microglial remodeling, neurovascular expression of the adhesion molecule intercellular cell adhesion molecule-1, prevented monocyte accumulation and neuroinflammatory signaling. Overall, these results indicate that HPA activation and corticosterone production during repeated social defeat stress are critical for monocyte release into circulation, glucocorticoid resistance of myeloid cells, and enhanced neurovascular cell adhesion molecule expression.
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