Distinct mechanisms underlie activation of hypothalamic neurosecretory neurons and their medullary catecholaminergic afferents in categorically different stress paradigms

Distinct mechanisms underlie activation of hypothalamic neurosecretory neurons and their medullary catecholaminergic afferents in categorically different stress paradigms
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DOI:
10.1073/pnas.93.6.2359
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发表时间:
1996-03-19
影响因子:
11.1
通讯作者:
Sawchenko, PE
Sawchenko, PE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Li, HY;Ericsson, A;Sawchenko, PE

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间歇性电足电击诱导表达促肾上腺皮质激素释放因子的小细胞神经分泌神经元和下丘脑室旁核(PVH)的其他内脏神经细胞类型中c-fos表达。由于孤束核和延髓腹外侧区的儿茶酚胺能神经元构成投射到PVH的足电击反应细胞的优势位点,这些被评价为下丘脑神经内分泌反应的候选传入介质。将带有该投射系统的不连续单侧横切的大鼠暴露于单次30分钟的足电击过程,并在2小时后处死。尽管同侧的胺能神经支配减少,但休克诱导的Fos蛋白和促肾上腺皮质激素释放因子mRNA在两侧脑PVH中的上调在强度和分布上是相当的。然而,这种损伤确实导致同侧延髓胺能神经元中Fos表达的显著减少,这些结果与在全身性细胞因子(白细胞介素1)挑战范例中获得的结果形成鲜明对比,其中类似的切口消融了同侧PVH中的Fos反应,但在同侧髓质中观察到的诱导保持不变。我们的结论是:(i)足底电击诱导的髓质胺能神经元激活是应激的继发性后果,通过我们的消融横断的下行投射介导,(ii)应激诱导的髓质胺能神经元激活不一定预示着这些细胞群参与驱动下丘脑内脏对给定应激源的反应,和(iii)尽管下丘脑效应神经元及其传入神经元的补体有惊人的相似性,但不同类型的应激可能会激活它们,不同的机制可能是每个下丘脑适应性反应的基础。
Intermittent electrical footshock induces c-fos expression in parvocellular neurosecretory neurons expressing corticotropin-releasing factor and in other visceromotor cell types of the paraventricular hypothalamic nucleus (PVH), Since catecholaminergic neurons of the nucleus of the solitary tract and ventrolateral medulla make up the dominant loci of footshock-responsive cells that project to the PVH, these were evaluated as candidate afferent mediators of hypothalamic neuroendocrine responses, Rats bearing discrete unilateral transections of this projection system were exposed to a single 30-min footshock session and sacrificed 2 hr later. Despite depletion of the aminergic innervation on the ipsilateral side, shock-induced up-regulation of Fos protein and corticotropin-releasing factor mRNA were comparable in strength and distribution in the PVH on both sides of the brain, This lesion did, however, result in a substantial reduction of Fos expression in medullary aminergic neurons on the ipsilateral side, These results contrast diametrically with those obtained in a systemic cytokine (interleukin 1) challenge paradigm, where similar cuts ablated the Fos response in the ipsilateral PVH but left intact the induction seen in the ipsilateral medulla. We conclude that (i) footshock-induced activation of medullary aminergic neurons is a secondary consequence of stress, mediated via a descending projection transected by our ablation, (ii) stress-induced activation of medullary aminergic neurons is not necessarily predictive of an involvement of these cell groups in driving hypothalamic visceromotor responses to a given stressor, and (iii) despite striking similarities in the complement of hypothalamic effector neurons and their afferents that may be activated by stresses of different types, distinct mechanisms may underlie adaptive hypothalamic responses in each.