Impaired stress and interleukin-1beta--induced hypothalamic expression of the neuronal activation marker FOS in cholestatic rats.
Both interleukin (IL)-1beta and psychological stress activate the hypothalamic-pituitary-adrenal (HPA) axis by stimulating neuronal activity within the paraventricular nucleus of the hypothalamus via different pathways. Because it has been shown previously that cholestatic rats show defective cytokine- and stress-induced HPA axis activation, neuronal activation in the paraventricular nucleus of rats with cholestasis caused by bile duct resection and in noncholestatic sham-resected (sham) controls was examined. To do this, the expression of the neuronal activation marker FOS in the hypothalamic paraventricular nucleus of bile duct-resected (BDR) and sham rats exposed to restraint stress and intracerebroventricularly infused IL-1beta, two stimuli known to activate the HPA axis by stimulating neurons in the paraventricular nucleus, was quantitated. BDR rats showed decreased FOS expression in the paraventricular nucleus after both stimuli compared with similarly treated sham controls. These data show that BDR rats show an impaired ability to activate hypothalamic neurons within the paraventricular nucleus and suggest that hypofunctioning of the HPA axis in response to immune (i.e., IL-1beta) and psychological stressors, which have been documented previously for BDR rats, may be caused by a specific defect in the intracellular machinery involved in the activation of neurons within the hypothalamic paraventricular nucleus.
Swain
M G
MG
Liver Unit, Gastrointestinal Research Group, Health Sciences Center, University of Calgary, Alberta, Canada.
Maric
M
M
D000818:Animals; D015415:Biomarkers; D002779:Cholestasis / Q000378:metabolism*; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*
D015415:Biomarkers; D007375:Interleukin-1; D016760:Proto-Oncogene Proteins c-fos