Abstract
Early life adversity and chronic inflammation have both been associated with cognitive impairment and neural compromise. In this study, we investigated the interactions between a history of chronic adolescent stress (CAS) and repeated endotoxin exposure on behavior, synaptic mitochondria, and microglia in adult male and female Wistar rats. Adult rats from chronic stress and control conditions were exposed to either repeated endotoxin (lipopolysaccharide; LPS) or saline injections every 3 days for 9 weeks. In both sexes, repeated LPS, regardless of stress history, impaired working memory in the Y maze. Regarding spatial memory, LPS impaired function for females; whereas, CAS altered function in males. Although males had an increase in anxiety-like behavior shortly after CAS, there were no long-term effects on anxiety-like behavior or social interaction observed in males or females. Stress did not alter synaptic mitochondrial function in either sex. Repeated LPS altered synaptic mitochondrial function such that ATP production was increased in females only. There were no observed increases in IBA-1 positive cells within the hippocampus for either sex. However, LPS and CAS altered microglia morphology in females. Impact of repeated LPS was evident at the terminal endpoint with increased spleen weight in both sexes and decreased adrenal weight in males only. Circulating cytokines were not impacted by repeated LPS at the terminal endpoint, but evidence of CAS effects on cytokines in females were evident. These data suggest a long-term impact of chronic stress and an impact of repeated endotoxin challenge in adulthood; however, not all physiological and behavioral metrics examined were impacted by the paradigm employed in this study and the two environmental challenges rarely interacted.
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No potential conflict of interest was reported by the author(s).
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Notes on contributors
A. J. Wegener
Amy. J. Wegener is a Ph.D. candidate in Neuroscience at Virginia Commonwealth University specializing in the neural consequences of pair bond disruption and inflammation.
M. M. Hyer
Molly M. Hyer, Ph.D., is director of Research Development and Innovation for the Institute of Women’s Health at Virginia Commonwealth University and Program Administrator for Building Interdisciplinary Research Careers in Women’s Health (BIRCWH).
I. Targett
Imogen Targett, completed degrees in biology and neuroscience and is now working as an industry Scientist.
A. Kloster
Alix Kloster completed aher Master of Science in Anatomy & Neurobiology, then obtained her Doctor of Dental Surgery (DDS) from Virginia Commonwealth University.
G. A. Shaw
Gladys Shaw, Ph.D., completed aher Ph.D. in Neuroscience at Virginia Commonwealth University and is currently a Senior Scientist.
A. M. M. Rodriguez
A. M. M. Rodriguez completed aher Bachelor of Science in biology at Virginia Commonwealth University.
S. K. Dyer
Samya K. Dyer, MP H, completed degrees in biology and psychology at Virginia Commonwealth University and holds a master’s in public health.
G. N. Neigh
Gretchen N. Neigh, Ph.D., is a Professor of Anatomy & Neurobiology. Dr. Neigh is director of Translational Research for the VCU Institute of Women’s Health, co-director of research for BIRCWH, and co-director for the Clinical and Translational Sciences PhD Program at Virginia Commonwealth University.