Interleukin-1-induced plasticity of hypothalamic CRH neurons and long-term stress hyperresponsiveness.
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-1 beta (5 micrograms/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.
Tilders
F J
FJ
Research Institute Neurosciences Free University, Department of Pharmacology, Amsterdam, The Netherlands.
Schmidt
E D
ED
D000818:Animals; D002908:Chronic Disease; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*
D007375:Interleukin-1; D003346:Corticotropin-Releasing Hormone