Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 97, Issue -, Pages 135-149Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2021.07.005
Keywords
Anxiety; Astrocyte hypertrophy; Cognitive and mood function; Hippocampal neurogenesis; Microglial activation; Neuroinflammation; Object location memory; Pattern separation; Running exercise
Categories
Funding
- Department of Veterans Affairs (VA Merit Award) [I01BX000883]
- Department of Defense [W81XWH-16-1-0480, W81XWH-17-1-0447]
- National Institutes of Health [R01NS106907-01]
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Moderate and intermittent physical exercise shows promise in improving cognitive and mood function in veterans with Gulf War Illness, while also suppressing neuroinflammation and enhancing hippocampal neurogenesis.
Persistent cognitive and mood impairments in Gulf War Illness (GWI) are associated with chronic neuro -inflammation, typified by hypertrophied astrocytes, activated microglia, and increased proinflammatory medi-ators in the brain. Using a rat model, we investigated whether a simple lifestyle change such as moderate voluntary physical exercise would improve cognitive and mood function in GWI. Because veterans with GWI exhibit fatigue and post-exertional malaise, we employed an intermittent voluntary running exercise (RE) regimen, which prevented exercise-induced stress. The GWI rats were provided access to running wheels three days per week for 13 weeks, commencing ten weeks after the exposure to GWI-related chemicals and stress (GWI-RE group). Groups of age-matched sedentary GWI rats (GWI-SED group) and naive rats were maintained par-allelly. Interrogation of rats with behavioral tests after the 13-week RE regimen revealed improved hippocampus-dependent object location memory and pattern separation function and reduced anxiety-like behavior in the GWI-RE group compared to the GWI-SED group. Moreover, 13 weeks of RE in GWI rats significantly reversed activated microglia with short and less ramified processes into non-inflammatory/antiinflammatory microglia with highly ramified processes and reduced the hypertrophy of astrocytes. Moreover, the production of new neurons in the hippocampus was enhanced when examined eight weeks after the commencement of RE. Notably, increased neurogenesis continued even after the cessation of RE. Collectively, the results suggest that even a moderate, intermittent physical exercise has the promise to improve brain function in veterans with GWI in association with suppression of neuroinflammation and enhancement of hippocampal neurogenesis.
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