title: Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons.
abstract: Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects. In rodents, NPS is expressed in a few pontine cell clusters. Its receptor (NPSR1) is, however, widely distributed in the brain. The anxiolytic and arousal-promoting effects of NPS make the NPS-NPSR1 system an interesting potential drug target in mood-related disorders. However, so far possible disease-related mechanisms involving NPS have only been studied in rodents. To validate the relevance of these animal studies for i.a. drug development, we have explored the distribution of NPS-expressing neurons in the human pons using in situ hybridization and stereological methods and we compared the distribution of NPS mRNA expressing neurons in the human and rat brain. The calculation revealed a total number of 22,317 ± 2411 NPS mRNA-positive neurons in human, bilaterally. The majority of cells (84%) were located in the parabrachial area in human: in the extension of the medial and lateral parabrachial nuclei, in the Kölliker-Fuse nucleus and around the adjacent lateral lemniscus. In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus. In addition, we identified a smaller cell cluster (11% of all NPS cells) in the pontine central gray matter both in human and rat, which has not been described previously even in rodents. We also examined the distribution of NPSR1 mRNA-expressing neurons in the human pons. These cells were mainly located in the rostral laterodorsal tegmental nucleus, the cuneiform nucleus, the microcellular tegmental nucleus region and in the periaqueductal gray. Our results show that both NPS and NPSR1 in the human pons are preferentially localized in regions of importance for integration of visceral autonomic information and emotional behavior. The reported interspecies differences must, however, be considered when looking for targets for new pharmacotherapeutical interventions.
authors.affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Csaba
authors.initials: C
authors.lastname: Adori
authors.affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Swapnali
authors.initials: S
authors.lastname: Barde
authors.affiliation: Geriatric Department, Institute for Clinical Medicine, Oslo University Oslo, Norway.
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet Stockholm, Sweden ; Science for Life Laboratory, Albanova University Center, Royal Institute of Technology Stockholm, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine Irvine, CA, USA ; Department of Pharmacology, University of California, Irvine Irvine, CA, USA ; Department of Molecular Biology and Biochemistry, University of California, Irvine Irvine, CA, USA.
authors.forename: Rainer R
authors.initials: RR
authors.lastname: Reinscheid
authors.affiliation: Institute of Neurology, Medical University of Vienna Vienna, Austria.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
keywords: Neuropeptide S (NPS); anxiety; arousal; deep brain stimulation (DBS); human brain; parabrachial; periaqueductal gray; sudden infant death syndrome