Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons
2015 (English)In: Frontiers in Neuroanatomy, ISSN 1662-5129, E-ISSN 1662-5129, Vol. 9Article in journal (Refereed) Published
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 Kolliker-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.
Place, publisher, year, edition, pages
[Adori, Csaba; Barde, Swapnali; Hokfelt, Tomas] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. [Bogdanovic, Nenad] Univ Oslo, Inst Clin Med, Dept Geriatr, Oslo, Norway. [Uhlen, Mathias] Karolinska Inst, Dept Neurosci, Sci Life Lab, S-17177 Stockholm, Sweden. [Uhlen, Mathias] Royal Inst Technol, Albanova Univ Ctr, Sci Life Lab, Stockholm, Sweden. [Reinscheid, Rainer R.] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA USA. [Reinscheid, Rainer R.] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA. [Reinscheid, Rainer R.] Univ Calif Irvine, Dept Biochem & Mol Biol, Irvine, CA USA. [Kovacs, Gabor G.] Med Univ Vienna, Inst Neurol, Vienna, Austria., 2015. Vol. 9
Neuropeptide S (NPS), anxiety, arousal, deep brain stimulation (DBs), human brain, parabrachial, periaqueductal gray, sudden infant death syndrome
IdentifiersURN: urn:nbn:se:kth:diva-176363DOI: 10.3389/fnana.2015.00126ISI: 000362687400001ScopusID: 2-s2.0-84943180507OAI: oai:DiVA.org:kth-176363DiVA: diva2:867030
QC 201511042015-11-042015-11-032015-11-04Bibliographically approved