کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5040598 | 1473902 | 2017 | 12 صفحه PDF | دانلود رایگان |
- Low maternal care heightens febrile response to lipopolysaccharide challenge in rats.
- Low maternal care increases corticosterone and spleen glucocorticoid receptors.
- Low maternal care reduces plasma IL-6 and increases central IL-6 expression.
- RU-486 eliminates differences in LPS fever based on early life maternal care.
- Differential sensitivity to RU-486-LPS challenge based on early maternal care.
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 50 µg/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.
Journal: Brain, Behavior, and Immunity - Volume 65, October 2017, Pages 239-250