Response to LPS: Brainstem and hypothalamic pathways

Indiana Univ-Purdue Univ At Indianapolis, Indianapolis IN

Investigators

Abstract

DESCRIPTION (provided by applicant): Signaling pathways in the brain that mediate the physiological components of the response to a bacterial infection - including fever accompanied by tachycardia and activation of the hypothalamic-pituitary adrenal axis - are still unknown. To address this question, I plan to study the role of the dorsomedial hypothalamus (DMH) and the raphe pallidus (RP) in the changes caused by systemic administration of lipopolysaccharide (LPS), a model for the innate immune response in rats. I hypothesize that the DMH mediates increases in body temperature, heart rate and plasma adrenocorticotropic hormone (ACTH) induced by systemic administration of LPS in conscious rats, and that the RP specifically mediates increases in body temperature and heart rate induced by systemic administration of LPS in conscious rats via signaling from the DMH. Chemical inhibition with muscimol, a neuronal inhibitor, will be used to assess the role of the DMH and the RP in the physiological components of the response to LPS, and anatomic correlates will be examined using combined retrograde tracing and fos immunocytochemistry.