Premium
Interleukin‐1‐Induced Plasticity of Hypothalamic CRH Neurons and Long‐Term Stress Hyperresponsiveness a
Author(s) -
TILDERS FRED J. H.,
SCHMIDT E. DONNE
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb09550.x
Subject(s) - endocrinology , medicine , corticotropin releasing hormone , receptor , hypothalamus , interleukin , receptor antagonist , antagonist , cytokine
A bstract : Infections and endotoxin (LPS) can affect hypothalamic CRH neurons and activate the HPA system. This can be prevented by IL‐1 receptor antagonist and mimicked by IL‐1. Chronic activation of the HPA system by repeated or chronic administration of IL‐1 (1 week) to rats is associated with plastic changes in hypothalamic CRH neurons. Single administration IL‐1β (5 μg/kg i.p.) to male Wistar or Lewis rats induced a similar form of neuroplasticity 1‐3 weeks later. This is characterized by a selective increase in coproduction, costorage, and cosecretion of AVP in hypothalamic CRH neurons. Exposure of IL‐1‐primed rats 1‐2 weeks later to foot shocks or IL‐1 resulted in exaggerated ACTH and CORT responses as compared to vehicle‐primed controls. Thus, rats are hyperresponsive to stressors weeks after IL‐1 exposure. In IL‐1‐primed animals, CRH binding and CRH‐ and V1b receptor mRNA levels in the pituitary glands are not altered by IL‐1 exposure 2 weeks earlier. We conclude that IL‐1‐induced, long‐lasting hyperresponsiveness to stressors is primarily caused by functional alterations in the brain that may be directly related to observed plasticity of hypothalamic CRH neurons.