Neuropeptide S promotes wakefulness through activation of the posterior hypothalamic histaminergic and orexinergic neurons

详细信息	查看全文 | 推荐本文 |

• 作者：P. Zhao¹ ; Y.F. Shao¹ ; M. Zhang ; K. Fan ; X.P. Kong ; R. Wang ; Y.P. Hou ; ^{houyiping@lzu.edu.cn}
• 关键词：neuropeptide S ; sleep-waking states ; c-Fos ; histamine neuron ; orexin neuron ; cortical activation
• 刊名：Neuroscience
• 出版年：2012
• 期刊代码：50_03064522
• 类别：neu
• 出版时间：5 April, 2012
• 卷：207
• 期：Complete
• 页码：218-226
• 文件大小：2719 K

摘要

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卤3.2 and 64.9卤2.1 min, respectively, vs. 41.4卤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.