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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 NPS mRNA-positive neurons in human and rat pons. (A,D) Schematic drawings from the atlas by Paxinos et al. (2012), indicating distribution of NPS mRNA-positive cell bodies (red dots) at two different levels (Obex +23 and +24). All schematic drawings are presented in higher magnification in the Supplementary Material. Boxed area in (A,D) show (B,E), respectively. (B, C,E,F) NPS mRNA-positive neurons belonging to the periventricular cluster in the central pontine gray matter adjacent to the posterodorsal tegmental nucleus (B,C), and to the sparse pericoerulear cells dorsally, adjacent to the locus coeruleus (E,F; the numerous, pigmented and autofluorescent locus coeruleus neurons are indicated with asterisks and the NPS mRNA-positive neurons indicated with arrows, both in F). Boxed area in (B,E) show (C,F), respectively. (G–I) Comparison of peri-coerulear NPS mRNA-postive neurons in the rat (G) and human (H,I). The boxed area in (H) is shown in (I). Note the compact cluster of neurons with high mRNA-expression level of NPS in rat (G, arrow), contrasting the very few scattered neurons around the locus coeruleus in human (I, arrow). The locus coeruleus is surrounded by dashed line in (G,H); the human noradrenergic locus coeruleus neurons appear as autofluorescent pigmented cells, indicated with stars in (I). (A,D) are reproduced from Paxinos et al. (2012), with permission. Scale bars: 200 μm (C), (F–H); 500 μm (B,E); 50 μm (I).
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Figure 4: Distribution of NPS mRNA-positive neurons in human and rat pons. (A,D) Schematic drawings from the atlas by Paxinos et al. (2012), indicating distribution of NPS mRNA-positive cell bodies (red dots) at two different levels (Obex +23 and +24). All schematic drawings are presented in higher magnification in the Supplementary Material. Boxed area in (A,D) show (B,E), respectively. (B, C,E,F) NPS mRNA-positive neurons belonging to the periventricular cluster in the central pontine gray matter adjacent to the posterodorsal tegmental nucleus (B,C), and to the sparse pericoerulear cells dorsally, adjacent to the locus coeruleus (E,F; the numerous, pigmented and autofluorescent locus coeruleus neurons are indicated with asterisks and the NPS mRNA-positive neurons indicated with arrows, both in F). Boxed area in (B,E) show (C,F), respectively. (G–I) Comparison of peri-coerulear NPS mRNA-postive neurons in the rat (G) and human (H,I). The boxed area in (H) is shown in (I). Note the compact cluster of neurons with high mRNA-expression level of NPS in rat (G, arrow), contrasting the very few scattered neurons around the locus coeruleus in human (I, arrow). The locus coeruleus is surrounded by dashed line in (G,H); the human noradrenergic locus coeruleus neurons appear as autofluorescent pigmented cells, indicated with stars in (I). (A,D) are reproduced from Paxinos et al. (2012), with permission. Scale bars: 200 μm (C), (F–H); 500 μm (B,E); 50 μm (I).

Mentions: The NPS mRNA-expressing neurons are localized in pons, between Obex +20 and Obex +32 mm and distributed in three distinct areas/clusters. (i) The “peri-ventricular cluster”: sparse cells in the central gray matter (CGPn) adjacent to the posterodorsal tegmental nucleus (PDTg) and ventral to the fourth ventricle (Figures 4A–C); (ii) the “peri-coerulear neurons”: very few labeled cells localized dorsally, adjacent to the LC. These cells sometimes intermingle with the LC group, but the pigmented LC noradrenergic neurons were never labeled (Figures 4D–F,H,I); (iii) the “PB cluster”: most of the pontine NPS-expressing neurons belong to this cell group, which starts at Obex +22 mm and ends at around Obex +32 mm. Many labeled cells were found ventral to the superior cerebellar peduncule (scp), in the external part of the medial and lateral PB nuclei (EMPB, ELPB, respectively) and sometimes in the Kölliker-Fuse KF) nucleus (Figures 4D, 5A–C). At Obex +26 mm, the PB cluster split into two sub-clusters surrounding the lateral lemniscus (ll). Thus, one cell group is localized ventral-lateral to the scp but medial to the lateral lemniscus, while the other one is lying on the lateral side of the lateral lemniscus (Figures 5D–F). From approximately Obex +28 mm, some labeled cells were detected in the ventral and intermediate nuclei of the lateral lemniscus (VLL, ILL, respectively; Figures 5G–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)

Distribution of NPS mRNA-positive neurons in human and rat pons. (A,D) Schematic drawings from the atlas by Paxinos et al. (2012), indicating distribution of NPS mRNA-positive cell bodies (red dots) at two different levels (Obex +23 and +24). All schematic drawings are presented in higher magnification in the Supplementary Material. Boxed area in (A,D) show (B,E), respectively. (B, C,E,F) NPS mRNA-positive neurons belonging to the periventricular cluster in the central pontine gray matter adjacent to the posterodorsal tegmental nucleus (B,C), and to the sparse pericoerulear cells dorsally, adjacent to the locus coeruleus (E,F; the numerous, pigmented and autofluorescent locus coeruleus neurons are indicated with asterisks and the NPS mRNA-positive neurons indicated with arrows, both in F). Boxed area in (B,E) show (C,F), respectively. (G–I) Comparison of peri-coerulear NPS mRNA-postive neurons in the rat (G) and human (H,I). The boxed area in (H) is shown in (I). Note the compact cluster of neurons with high mRNA-expression level of NPS in rat (G, arrow), contrasting the very few scattered neurons around the locus coeruleus in human (I, arrow). The locus coeruleus is surrounded by dashed line in (G,H); the human noradrenergic locus coeruleus neurons appear as autofluorescent pigmented cells, indicated with stars in (I). (A,D) are reproduced from Paxinos et al. (2012), with permission. Scale bars: 200 μm (C), (F–H); 500 μm (B,E); 50 μm (I).
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Figure 4: Distribution of NPS mRNA-positive neurons in human and rat pons. (A,D) Schematic drawings from the atlas by Paxinos et al. (2012), indicating distribution of NPS mRNA-positive cell bodies (red dots) at two different levels (Obex +23 and +24). All schematic drawings are presented in higher magnification in the Supplementary Material. Boxed area in (A,D) show (B,E), respectively. (B, C,E,F) NPS mRNA-positive neurons belonging to the periventricular cluster in the central pontine gray matter adjacent to the posterodorsal tegmental nucleus (B,C), and to the sparse pericoerulear cells dorsally, adjacent to the locus coeruleus (E,F; the numerous, pigmented and autofluorescent locus coeruleus neurons are indicated with asterisks and the NPS mRNA-positive neurons indicated with arrows, both in F). Boxed area in (B,E) show (C,F), respectively. (G–I) Comparison of peri-coerulear NPS mRNA-postive neurons in the rat (G) and human (H,I). The boxed area in (H) is shown in (I). Note the compact cluster of neurons with high mRNA-expression level of NPS in rat (G, arrow), contrasting the very few scattered neurons around the locus coeruleus in human (I, arrow). The locus coeruleus is surrounded by dashed line in (G,H); the human noradrenergic locus coeruleus neurons appear as autofluorescent pigmented cells, indicated with stars in (I). (A,D) are reproduced from Paxinos et al. (2012), with permission. Scale bars: 200 μm (C), (F–H); 500 μm (B,E); 50 μm (I).
Mentions: The NPS mRNA-expressing neurons are localized in pons, between Obex +20 and Obex +32 mm and distributed in three distinct areas/clusters. (i) The “peri-ventricular cluster”: sparse cells in the central gray matter (CGPn) adjacent to the posterodorsal tegmental nucleus (PDTg) and ventral to the fourth ventricle (Figures 4A–C); (ii) the “peri-coerulear neurons”: very few labeled cells localized dorsally, adjacent to the LC. These cells sometimes intermingle with the LC group, but the pigmented LC noradrenergic neurons were never labeled (Figures 4D–F,H,I); (iii) the “PB cluster”: most of the pontine NPS-expressing neurons belong to this cell group, which starts at Obex +22 mm and ends at around Obex +32 mm. Many labeled cells were found ventral to the superior cerebellar peduncule (scp), in the external part of the medial and lateral PB nuclei (EMPB, ELPB, respectively) and sometimes in the Kölliker-Fuse KF) nucleus (Figures 4D, 5A–C). At Obex +26 mm, the PB cluster split into two sub-clusters surrounding the lateral lemniscus (ll). Thus, one cell group is localized ventral-lateral to the scp but medial to the lateral lemniscus, while the other one is lying on the lateral side of the lateral lemniscus (Figures 5D–F). From approximately Obex +28 mm, some labeled cells were detected in the ventral and intermediate nuclei of the lateral lemniscus (VLL, ILL, respectively; Figures 5G–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.