期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 55, 期 -, 页码 17-24出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2015.08.022
关键词
Microglia; TNF-alpha; Working memory; Acute stress; Etanercept; 3D morphological analysis; Hippocampus; Water-immersion resistant stress
资金
- KAKENHI - the Japan Society for the Promotion of Science [26713039, 26860933, 25293252, 24650227]
- Innovative Areas Glia Assembly of The Ministry of Education, Culture, Sports, Science, and Technology, Japan [25117011]
- Japan Agency for Medical Research and Development (AMED) -The Japanese Ministry of Health, Labour and Welfare (Seishin-Syogai Taisaku-Jigyo) [H27]
- Young Principal Investigators' Research Grant of Innovation Center for Medical Redox Navigation, Kyushu University
- Takeda Medical Research Foundation
- SENSHIN Medical Research Foundation
- Grants-in-Aid for Scientific Research [24650227, 25293252, 25117001, 25117011, 26860933, 26713039] Funding Source: KAKEN
The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2 h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-alpha levels were significantly elevated after acute stress, and acute stress-induced TNF-alpha was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-alpha were not elevated after acute stress. Etanercept (TNF-alpha inhibitor) recovered working memory deficits in accordance with hippocampal TNF-alpha reductions. Overall, results suggest that TNF-a from hippocampal microglia is a key contributor to early-stage stress-to-mental responses. (C) 2015 Elsevier Inc. All rights reserved.
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