title: Exploring the role of neuropeptide S in the regulation of arousal: a functional anatomical study.
abstract: Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep.
authors.affiliation: Retzius Laboratory, Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177, Stockholm, Sweden. adorics@gmail.com.
authors.forename: Csaba
authors.initials: C
authors.lastname: Adori
authors.affiliation: Retzius Laboratory, Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177, Stockholm, Sweden.
authors.forename: Swapnali
authors.initials: S
authors.lastname: Barde
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, 1089, Budapest, Hungary.|Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4, 1089, Budapest, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Vas
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck (CMBI), Leopold-Franzens-University of Innsbruck, Innrain 80-82/III, 6020, Innsbruck, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Ebner
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, 17177, Stockholm, Sweden.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, 17177, Stockholm, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Svensson
authors.affiliation: Section of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Tomtebodavägen 18A, 17177, Stockholm, Sweden.
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck (CMBI), Leopold-Franzens-University of Innsbruck, Innrain 80-82/III, 6020, Innsbruck, Austria.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
authors.affiliation: Department of Pharmaceutical Sciences, University of California Irvine, Irvine, CA, 92697, USA.
authors.forename: Rainer R
authors.initials: RR
authors.lastname: Reinscheid
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet, 17165, Stockholm, Sweden.|Science for Life Laboratory, Albanova University Center, Royal Institute of Technology, 17165, Stockholm, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Department of Medical Science Cancer Pharmacology and Computational Medicine, Academiska Sjukhuset, Uppsala University, 75185, Uppsala, Sweden.
authors.forename: Kim
authors.initials: K
authors.lastname: Kultima
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, 1089, Budapest, Hungary.|Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4, 1089, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Bagdy
authors.affiliation: Retzius Laboratory, Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
mesh_terms: D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000378:metabolism; D001143:Arousal; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism; D019004:Galanin / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D011301:Preoptic Area / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D018013:Receptors, Neuropeptide / Q000378:metabolism; D012890:Sleep; D012892:Sleep Deprivation / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; C568280:neuropeptide S receptor, rat; C534458:neuropeptide S, rat; D018698:Glutamic Acid; D019004:Galanin
keywords: Arousal; Dopamine; Glutamate; Neuropeptide S (NPS); Preoptic area; Septum; Sleep; Substance P; Transmitter release; Wakefulness