NORADRENERGIC INPUTS TO THE PARAVENTRICULAR HYPOTHALAMUS CONTRIBUTE TO HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND CENTRAL Fos ACTIVATION IN RATS AFTER ACUTE SYSTEMIC ENDOTOXIN EXPOSURE
NORADRENERGIC INPUTS TO THE PARAVENTRICULAR HYPOTHALAMUS CONTRIBUTE TO HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND CENTRAL Fos ACTIVATION IN RATS AFTER ACUTE SYSTEMIC ENDOTOXIN EXPOSURE
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DOI：
10.1016/j.neuroscience.2008.08.011
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发表时间：
2008-10-28
期刊：
影响因子：
3.3
通讯作者：
Rinaman, L.
中科院分区：
文献类型：
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作者：
Bienkowski, M. S.;Rinaman, L.
孤立束核（NST）和尾侧腹外髓核（VLM）内的去甲肾上腺素能（NA）神经元支配下丘脑室旁核（PVN），启动和调节下丘脑-垂体-肾上腺（HPA）轴对感受性应激的反应。全身性内毒素（即细菌脂多糖，LIPS）激活NST和VLM内的NA神经元，这些神经元投射到PVN和其他接收内感受信号的大脑区域。本研究考察了轴突输入PVN的NA神经元是否需要LPS激活PVN和其他脑内感受相关区域的Fos表达，并增加血浆皮质酮。雄性Sprague-Dawley大鼠双侧立体定向显微注射DSAP（与抗多巴胺- β -羟化酶抗体结合的皂苷毒素，DbH）到PVN以破坏NA输入。对照大鼠在PVN内微注射载药或不注射PVN。2周后，DSAP大鼠和对照大鼠分别腹腔注射lip （200 μ g/kg BW）或生理盐水载药，2.5 ~ 3 h后灌注固定液。脑组织切片处理显示核Fos蛋白和细胞质DbH免疫标记。DSAP病变减少了PVN和终纹床核中的NA末端，减少了NST和VLM中NA细胞体的数量，减弱了LPS后PVN Fos的激活，减弱了LPS诱导的血浆皮质酮的升高。这些发现支持从后脑到下丘脑的NA投射对于HPA轴对全身免疫挑战的完整反应是必要的。(c) 2008 ibro。Elsevier Ltd.出版。版权所有。
Noradrenergic (NA) neurons within the nucleus of the solitary tract (NST) and caudal ventrolateral medulla (VLM) innervate the hypothalamic paraventricular nucleus (PVN) to initiate and modulate hypothalamic-pituitary-adrenal (HPA) axis responses to interoceptive stress. Systemic endotoxin (i.e. bacterial lipopolysaccharide, LIPS) activates NA neurons within the NST and VLM that project to the PVN and other brain regions that receive interoceptive signals. The present study examined whether NA neurons with axonal inputs to the PVN are necessary for LPS to activate Fos expression within the PVN and other interoceptive-related brain regions, and to increase plasma corticosterone. Male Sprague-Dawley rats received bilateral stereotaxic microinjections of DSAP (saporin toxin conjugated to an antibody against dopamine-beta-hydroxylase, DbH) into the PVN to destroy NA inputs. Control rats were microinjected with vehicle into the PVN or received no PVN injections. Two weeks later, DSAP and control rats were injected i.p. with LIPS (200 mu g/kg BW) or saline vehicle, and perfused with fixative 2.5-3 h later. Brain tissue sections were processed to reveal nuclear Fos protein and cytoplasmic DbH immunolabeling. DSAP lesions depleted NA terminals in the PVN and bed nucleus of the stria terminalis, reduced the number of NA cell bodies in the NST and VLM, attenuated PVN Fos activation after LPS, and attenuated LPS-induced increases in plasma corticosterone. These findings support the view that NA projections from hind-brain to hypothalamus are necessary for a full HPA axis response to systemic immune challenge. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.