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

Authors: Zhao, P  Shao, YF  Zhang, M  Fan, K  Kong, XP  Wang, R  Hou, YP 
Citation: Zhao P, etal., Neuroscience. 2012 Apr 5;207:218-26. doi: 10.1016/j.neuroscience.2012.01.022. Epub 2012 Jan 20.
Pubmed: (View Article at PubMed) PMID:22300983
DOI: Full-text: DOI:10.1016/j.neuroscience.2012.01.022

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.


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CRRD Object Information
CRRD ID: 9831203
Created: 2015-03-03
Species: All species
Last Modified: 2015-03-03
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.