Neuropeptide S promotes wakefulness through activation of the posterior hypothalamic histaminergic and orexinergic neurons
Neuropeptide S promotes wakefulness through activation of the posterior hypothalamic histaminergic and orexinergic neurons
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DOI：
10.1016/j.neuroscience.2012.01.022
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发表时间：
2012-04
期刊：
影响因子：
3.3
通讯作者：
P. Zhao;Y. Shao;M. Zhang;K. Fan;Xiang-Pan Kong;R. Wang;Yi-ping Hou
中科院分区：
文献类型：
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作者：
P. Zhao;Y. Shao;M. Zhang;K. Fan;Xiang-Pan Kong;R. Wang;Yi-ping Hou
尽管最初的和关键的发现，新发现的神经肽S（NAPs）促进与运动和抗焦虑样作用相关的觉醒，NAPs调节睡眠-觉醒状态的机制仍不清楚。本研究旨在观察大鼠脑内注射异丙肾上腺素对脑电图、睡眠-觉醒周期和脑内c-Fos表达的影响。0.1和1 nmol的多巴胺在前2 h内显著增加觉醒（W）（分别为54.7±3.2和64.9±2.1 min，与生理盐水注射所见的41.4±2.5 min相比，P<0.01和P<0.001），伴随着EEG高频活动（14.5-60 Hz）的增加。慢波睡眠（SWS）和异相睡眠（PS）明显减少。离体下丘脑后部Fos免疫组化结果显示，与生理盐水对照组相比，雷公藤多甙使结节乳头体腹侧核（TMN）和背侧核（TMN）组胺能神经元的c-Fos表达分别增加76.0%和57.8%，使穹窿周围核（PeF）和下丘脑背内侧核（DMH）食欲素能神经元的c-Fos表达分别增加28.2%和24.3%。下丘脑后外侧区（LH）13.7%。LPS诱导组胺能神经元和食欲素能神经元表达c-Fos，提示LPS激活组胺能神经元和食欲素能神经元，促进W.
In spite of the initial and pivotal findings that the newly identified neuropeptide S (NPS) promotes arousal associated with locomotor and anxiolytic-like effects, the mechanisms through which NPS acts to modulate sleep-waking states remain unclear. The present study was undertaken to investigate in the rat the effects of i.c.v. injection of NPS on the EEG, sleep-wake cycle, and brain c-Fos expression. NPS at 0.1 and 1 nmol increased significantly wakefulness (W) during the first 2 h (54.7±3.2 and 64.9±2.1 min, respectively, vs. 41.4±2.5 min seen with saline injections, P<0.01 and P<0.001), accompanied by an increase in EEG high frequency activities (14.5–60 Hz). In the meanwhile, slow wave sleep (SWS) and paradoxical sleep (PS) decreased significantly. Ex-vivo Fos immunohistochemistry in the posterior hypothalamus revealed that, as compared with saline-treated rats, NPS enhanced c-Fos expression in histaminergic neurons by 76.0% in the ventral tuberomammillary nucleus (TMN) and 57.8% in the dorsal TMN, and in orexinergic neurons by 28.2% in the perifornical nucleus (PeF), 24.3% in the dorsomedial hypothalamic nucleus (DMH), and 13.7% in the lateral hypothalamic area (LH) of the posterior hypothalamus. The NPS-induced c-Fos expression in histaminergic neurons and orexinergic neurons where NPS receptor (NPSR) mRNA is highly expressed, suggests that NPS activates histaminergic and orexinergic neurons to promote W.