Maternal care modulates the febrile response to lipopolysaccharide through differences in glucocorticoid receptor sensitivity in the rat.
|Title||Maternal care modulates the febrile response to lipopolysaccharide through differences in glucocorticoid receptor sensitivity in the rat.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Parent C, Nguyen H-B, Wen X, Diorio J, Meaney MJ, Zhang T-Y|
|Journal||Brain Behav Immun|
|Date Published||2017 Oct|
Early life adversity increases the risk for later infection. The febrile response is a potent mechanism to combat infection. We found that variations in maternal care influence the febrile response to 50µg/kg lipopolysaccharide (LPS) challenge in adult male rats. Offspring from low-licking/grooming (LG) mothers had an increased febrile response compared to offspring from high-LG mothers challenged with LPS. Low-LG offspring had reduced plasma IL-6 at one and two hours post challenge compared to high-LG offspring. IL-6 gene expression in the anterior hypothalamus was induced following LPS challenge in low-LG offspring but not in high-LG offspring at two hours post challenge. Occupancy of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) to the IL-6 promoter region in the anterior hypothalamus was greater in low-LG offspring treated with LPS than in high-LG offspring. These findings suggest greater activation of thermoregulatory neurons in the anterior hypothalamus of low-LG compared to high-LG offspring following LPS challenge. Low-LG offspring had greater plasma corticosterone levels following LPS challenge and they had enhanced glucocorticoid receptors (GR) in the spleen compared to high-LG offspring. Enhanced glucocorticoids and glucocorticoid receptor sensitivity associated with reduced IL-6 induction early post challenge in low-LG offspring. Challenge with RU-486 prior to LPS challenge eliminated differences in the febrile response between offspring of high and low-LG mothers. Individual differences in GR sensitivity may modulate differences in the febrile response to LPS challenge, exerting a long-term influence on the capacity to recover from infection.
|Alternate Journal||Brain Behav. Immun.|