Tilders F J, Schmidt E D
Research Institute Neurosciences Free University, Department of Pharmacology, Amsterdam, The Netherlands.
Ann N Y Acad Sci. 1998 May 1;840:65-73. doi: 10.1111/j.1749-6632.1998.tb09550.x.
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.
感染和内毒素（脂多糖）可影响下丘脑促肾上腺皮质激素释放激素（CRH）神经元并激活下丘脑-垂体-肾上腺（HPA）系统。这可通过白细胞介素-1受体拮抗剂预防，而白细胞介素-1可模拟这种作用。通过对大鼠反复或长期（1周）给予白细胞介素-1而导致的HPA系统慢性激活与下丘脑CRH神经元的可塑性变化有关。对雄性Wistar或Lewis大鼠单次腹腔注射白细胞介素-1β（5微克/千克），1至3周后会诱导出类似形式的神经可塑性。其特征是下丘脑CRH神经元中精氨酸加压素（AVP）的共产生、共储存和共分泌选择性增加。在1至2周后，将预先用白细胞介素-1处理的大鼠暴露于足部电击或白细胞介素-1下，与用赋形剂预处理的对照组相比，促肾上腺皮质激素（ACTH）和皮质酮（CORT）反应会增强。因此，大鼠在暴露于白细胞介素-1数周后对应激源的反应性增强。在用白细胞介素-1预处理的动物中，垂体中CRH结合以及CRH和V1b受体mRNA水平在2周前不受白细胞介素-1暴露的影响。我们得出结论，白细胞介素-诱导的、对应激源的长期高反应性主要是由大脑中的功能改变引起的，这些改变可能与观察到的下丘脑CRH神经元的可塑性直接相关。
