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Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons.

Adori C, Barde S, Bogdanovic N, Uhlén M, Reinscheid RR, Kovacs GG, Hökfelt T - Front Neuroanat (2015)

Bottom Line: Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects.In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.

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.

No MeSH data available.


Comparison of the distribution of NPS mRNA-positive with NPS-immunoreactive neurons in the rat brainstem 1—the periventricular cluster. (A) Schematic drawing from the atlas by Paxinos and Watson (2007), indicating distribution of NPS-positive cell bodies (arrows and red dots) around the fourth ventricle. All schematic drawings are presented in higher magnification in the Supplementary Material. (B) shows distribution of the transcript and (C) of the peptide immunoreactivity at approximately the same level. Note the similar distribution of the NPS neurons in the periventricular cluster visualized with in situ hybridization (NPS mRNA) and immunohistochemistry (NPS peptide). The section in (C) is from a colchichine-treated rat. (A) is reproduced from Paxinos and Watson (2007), with permission. Scale bar: 200 μm (C), applies to (B,C).
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Figure 7: Comparison of the distribution of NPS mRNA-positive with NPS-immunoreactive neurons in the rat brainstem 1—the periventricular cluster. (A) Schematic drawing from the atlas by Paxinos and Watson (2007), indicating distribution of NPS-positive cell bodies (arrows and red dots) around the fourth ventricle. All schematic drawings are presented in higher magnification in the Supplementary Material. (B) shows distribution of the transcript and (C) of the peptide immunoreactivity at approximately the same level. Note the similar distribution of the NPS neurons in the periventricular cluster visualized with in situ hybridization (NPS mRNA) and immunohistochemistry (NPS peptide). The section in (C) is from a colchichine-treated rat. (A) is reproduced from Paxinos and Watson (2007), with permission. Scale bar: 200 μm (C), applies to (B,C).

Mentions: Next, we examined, for a direct comparison, the distribution of NPS expressing neurons in adult Wistar rat both with in situ hybridization (transcript) and immunohistochemistry (peptide). In addition to the previously described NPS-expressing cell groups, we found a small cell cluster of NPS neurons medially, adjacent to the posterodorsal tegmental nucleus, just around the midline of the fourth ventricle at Bregma −9.8 to −9.6 mm (the “peri-ventricular cluster”; Figures 7A,B). In agreement with previous studies in rat (Xu et al., 2007), we noted mRNA expression also in (i) a compact cell cluster ventro-lateral to the LC with high numbers of NPS neurons (the “peri-coerulear cluster”; Figures 8A,B); (ii) a cell cluster in the lateral PB nucleus with low numbers of NPS mRNA-positive neurons (the “PB cluster”; Figures 8D,E); and (iii) a cluster lateral to the external part of lateral PB nucleus and dorso-lateral to the KF nucleus with high NPS expression (the “KF cluster”; Figures 8G,H). NPS protein expression in all four cell clusters was confirmed by immunohistochemistry using antibodies to NPS and shown in sections from colchichine-treated rats (Figures 7C, 8C,F,I). Notably, the prominent peri-coerulear NPS cell cluster in rat is virtually missing in human (cf. Figures 8A–C and Figure 4G with Figures 4D–F,H,I).


Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons.

Adori C, Barde S, Bogdanovic N, Uhlén M, Reinscheid RR, Kovacs GG, Hökfelt T - Front Neuroanat (2015)

Comparison of the distribution of NPS mRNA-positive with NPS-immunoreactive neurons in the rat brainstem 1—the periventricular cluster. (A) Schematic drawing from the atlas by Paxinos and Watson (2007), indicating distribution of NPS-positive cell bodies (arrows and red dots) around the fourth ventricle. All schematic drawings are presented in higher magnification in the Supplementary Material. (B) shows distribution of the transcript and (C) of the peptide immunoreactivity at approximately the same level. Note the similar distribution of the NPS neurons in the periventricular cluster visualized with in situ hybridization (NPS mRNA) and immunohistochemistry (NPS peptide). The section in (C) is from a colchichine-treated rat. (A) is reproduced from Paxinos and Watson (2007), with permission. Scale bar: 200 μm (C), applies to (B,C).
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Related In: Results  -  Collection

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Figure 7: Comparison of the distribution of NPS mRNA-positive with NPS-immunoreactive neurons in the rat brainstem 1—the periventricular cluster. (A) Schematic drawing from the atlas by Paxinos and Watson (2007), indicating distribution of NPS-positive cell bodies (arrows and red dots) around the fourth ventricle. All schematic drawings are presented in higher magnification in the Supplementary Material. (B) shows distribution of the transcript and (C) of the peptide immunoreactivity at approximately the same level. Note the similar distribution of the NPS neurons in the periventricular cluster visualized with in situ hybridization (NPS mRNA) and immunohistochemistry (NPS peptide). The section in (C) is from a colchichine-treated rat. (A) is reproduced from Paxinos and Watson (2007), with permission. Scale bar: 200 μm (C), applies to (B,C).
Mentions: Next, we examined, for a direct comparison, the distribution of NPS expressing neurons in adult Wistar rat both with in situ hybridization (transcript) and immunohistochemistry (peptide). In addition to the previously described NPS-expressing cell groups, we found a small cell cluster of NPS neurons medially, adjacent to the posterodorsal tegmental nucleus, just around the midline of the fourth ventricle at Bregma −9.8 to −9.6 mm (the “peri-ventricular cluster”; Figures 7A,B). In agreement with previous studies in rat (Xu et al., 2007), we noted mRNA expression also in (i) a compact cell cluster ventro-lateral to the LC with high numbers of NPS neurons (the “peri-coerulear cluster”; Figures 8A,B); (ii) a cell cluster in the lateral PB nucleus with low numbers of NPS mRNA-positive neurons (the “PB cluster”; Figures 8D,E); and (iii) a cluster lateral to the external part of lateral PB nucleus and dorso-lateral to the KF nucleus with high NPS expression (the “KF cluster”; Figures 8G,H). NPS protein expression in all four cell clusters was confirmed by immunohistochemistry using antibodies to NPS and shown in sections from colchichine-treated rats (Figures 7C, 8C,F,I). Notably, the prominent peri-coerulear NPS cell cluster in rat is virtually missing in human (cf. Figures 8A–C and Figure 4G with Figures 4D–F,H,I).

Bottom Line: Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects.In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.

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.

No MeSH data available.