Early hypothalamic activation of combined Fos and CRH41 immunoreactivity and of CRH41 release in push-pull cannulated rats after systemic endotoxin challenge.
We previously showed that intra-arterial endotoxin infusion (lipopolysaccharide [LPS]: 25 micrograms.kg-1) induced an early (15 min) and sustained (480 min) rise in plasma ACTH associated with delayed (60-120 min) increases in plasma concentrations of TNF alpha, IL-6, and IL-1 beta. In the present study, we followed the post-LPS time-course of immunocytochemical expression of Fos-like activity in CRH41 neurons whose immunolabeling was enhanced by icv colchicine pretreatment 48 h before the LPS, and CRH41 release in the push-pull cannulated median eminence of free-moving rats, in parallel with the ACTH response. The earliest Fos-like activity in IR-CHR41 neurons was detected 30 min post-LPS. Colchicine strongly inhibited the LPS-induced activation of Fos expression in single-labeled paraventricular neurons. CRH41 release in the median eminence displayed a biphasic stimulation pattern, with a first peak (+60%) at 15 min together with the ACTH surge, followed by a second rise beginning at 45 min and lasting more than 2 h. Thus, the early stage of the ACTH surge following a nonlethal endotoxin challenge (< 60 min) already involves the activation of CRH41-producing neurons.
Givalois
L
L
Endocrinological Neurobiology Laboratory, URA 1197 CNRS, University of Montpellier-2, France.
Siaud
P
P
Mekaouche
M
M
Ixart
G
G
Malaval
F
F
Assenmacher
I
I
Barbanel
G
G
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002404:Catheterization / Q000379:methods*; D003346:Corticotropin-Releasing Hormone / Q000032:analysis* / Q000378:metabolism; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone