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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.


Distribution of NPSR1 mRNA-positive neurons in the human pons. (A,B) Cresyl violet staining at Obex +35 mm (A) and schematic drawing from the same level showing distribution of transcript-positive cells (red dots; B). All schematic drawings are presented in higher magnification in the Supplementary Material. Boxed areas in (A,B) indicated with “E,” “F,” and “G” show (E,F,G), respectively. (C,D) NPSR1 neurons in the cuneiform nucleus in the same, cresyl violet stained section shown in bright- (C) and darkfield (D). (E–J) Darkfield micrographs showing NPSR1 neurons in the ventrolateral periaqueductal gray (E,H) and the cuneiform nucleus—microcellular tegmental nucleus—spinothalamic tract region (F,G,I,J). Boxes in (E,F,G) show (H,I,J), respectively. (B) is reproduced from the atlas of Paxinos et al. (2012), with permission. Scale bars: 1000 μm (A); 50 μm (C), applies to (C,D); 300 μm (E), applies to (E–G); 100 μm (H), applies to (H–J).
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Figure 9: Distribution of NPSR1 mRNA-positive neurons in the human pons. (A,B) Cresyl violet staining at Obex +35 mm (A) and schematic drawing from the same level showing distribution of transcript-positive cells (red dots; B). All schematic drawings are presented in higher magnification in the Supplementary Material. Boxed areas in (A,B) indicated with “E,” “F,” and “G” show (E,F,G), respectively. (C,D) NPSR1 neurons in the cuneiform nucleus in the same, cresyl violet stained section shown in bright- (C) and darkfield (D). (E–J) Darkfield micrographs showing NPSR1 neurons in the ventrolateral periaqueductal gray (E,H) and the cuneiform nucleus—microcellular tegmental nucleus—spinothalamic tract region (F,G,I,J). Boxes in (E,F,G) show (H,I,J), respectively. (B) is reproduced from the atlas of Paxinos et al. (2012), with permission. Scale bars: 1000 μm (A); 50 μm (C), applies to (C,D); 300 μm (E), applies to (E–G); 100 μm (H), applies to (H–J).

Mentions: Finally, we examined the distribution of the NPS receptor mRNA-expressing neurons in the pons between Obex +15 and Obex +37 mm (Figures 9A,B). Weak labeling of sparse cells was noted in the pontine central gray matter (CGPn), around the LC, ventral to the superior cerebellar penduncle in the medial PB—KF—lateral lemniscus region, and in the caudal part of the laterodorsal tegmental nucleus (LDTg–LDTgV; data not shown). In contrast, strong labeling was found in the rostral LDTg, in the cuneiform nucleus (Figures 9C,D), and medial to the parabigeminal nucleus (PBG) in the spinothalamic tract – microcellular tegmental nucleus (MiTg) region (Figures 9A,B,F,G,I,J). Also, numerous NPSR1 mRNA-expressing cells were noted in all divisions of the periaqueductal gray (dorsomedial, lateral, ventrolateral, raphe cap), especially in the ventrolateral part (VLPAG; Figures 9A,B,E,H). However, there was no NPSR1 mRNA-expression detected in the dorsal or medial raphe nuclei (data not shown).


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)

Distribution of NPSR1 mRNA-positive neurons in the human pons. (A,B) Cresyl violet staining at Obex +35 mm (A) and schematic drawing from the same level showing distribution of transcript-positive cells (red dots; B). All schematic drawings are presented in higher magnification in the Supplementary Material. Boxed areas in (A,B) indicated with “E,” “F,” and “G” show (E,F,G), respectively. (C,D) NPSR1 neurons in the cuneiform nucleus in the same, cresyl violet stained section shown in bright- (C) and darkfield (D). (E–J) Darkfield micrographs showing NPSR1 neurons in the ventrolateral periaqueductal gray (E,H) and the cuneiform nucleus—microcellular tegmental nucleus—spinothalamic tract region (F,G,I,J). Boxes in (E,F,G) show (H,I,J), respectively. (B) is reproduced from the atlas of Paxinos et al. (2012), with permission. Scale bars: 1000 μm (A); 50 μm (C), applies to (C,D); 300 μm (E), applies to (E–G); 100 μm (H), applies to (H–J).
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Figure 9: Distribution of NPSR1 mRNA-positive neurons in the human pons. (A,B) Cresyl violet staining at Obex +35 mm (A) and schematic drawing from the same level showing distribution of transcript-positive cells (red dots; B). All schematic drawings are presented in higher magnification in the Supplementary Material. Boxed areas in (A,B) indicated with “E,” “F,” and “G” show (E,F,G), respectively. (C,D) NPSR1 neurons in the cuneiform nucleus in the same, cresyl violet stained section shown in bright- (C) and darkfield (D). (E–J) Darkfield micrographs showing NPSR1 neurons in the ventrolateral periaqueductal gray (E,H) and the cuneiform nucleus—microcellular tegmental nucleus—spinothalamic tract region (F,G,I,J). Boxes in (E,F,G) show (H,I,J), respectively. (B) is reproduced from the atlas of Paxinos et al. (2012), with permission. Scale bars: 1000 μm (A); 50 μm (C), applies to (C,D); 300 μm (E), applies to (E–G); 100 μm (H), applies to (H–J).
Mentions: Finally, we examined the distribution of the NPS receptor mRNA-expressing neurons in the pons between Obex +15 and Obex +37 mm (Figures 9A,B). Weak labeling of sparse cells was noted in the pontine central gray matter (CGPn), around the LC, ventral to the superior cerebellar penduncle in the medial PB—KF—lateral lemniscus region, and in the caudal part of the laterodorsal tegmental nucleus (LDTg–LDTgV; data not shown). In contrast, strong labeling was found in the rostral LDTg, in the cuneiform nucleus (Figures 9C,D), and medial to the parabigeminal nucleus (PBG) in the spinothalamic tract – microcellular tegmental nucleus (MiTg) region (Figures 9A,B,F,G,I,J). Also, numerous NPSR1 mRNA-expressing cells were noted in all divisions of the periaqueductal gray (dorsomedial, lateral, ventrolateral, raphe cap), especially in the ventrolateral part (VLPAG; Figures 9A,B,E,H). However, there was no NPSR1 mRNA-expression detected in the dorsal or medial raphe nuclei (data not shown).

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.