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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.


NPS mRNA-positive neurons in human pons (emulsion-dipped). (A,B) Labeled neurons (arrows) are seen in the periventricular cell cluster in the same section (A, brightfield, cresyl violet; B, darkfield). (C) High magnification showing one NPS mRNA-positive neuron (cresyl violet, brightfield). (D,E) Low power overview of the central pontine gray matter showing a few cells (arrow) in the periventricular NPS cell cluster (D, darkfield); (E) shows the same section (cresyl violet, brightfield). The posterodorsal tegmantal nucleus (PDTg) is surrounded by dashed line in (D,E). (F,G) Low power overview of the parabrachial area showing many labeled neurons (arrows) of the parabrachial cell cluster (F, darkfield); (G) shows same section (cresyl violet; brightfield). Scale bars: 100 μm (A), applies to (A,B); 25 μm (C); 500 μm (D), applies to (D,E); 1000 μm (F), applies to (F,G).
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Figure 3: NPS mRNA-positive neurons in human pons (emulsion-dipped). (A,B) Labeled neurons (arrows) are seen in the periventricular cell cluster in the same section (A, brightfield, cresyl violet; B, darkfield). (C) High magnification showing one NPS mRNA-positive neuron (cresyl violet, brightfield). (D,E) Low power overview of the central pontine gray matter showing a few cells (arrow) in the periventricular NPS cell cluster (D, darkfield); (E) shows the same section (cresyl violet, brightfield). The posterodorsal tegmantal nucleus (PDTg) is surrounded by dashed line in (D,E). (F,G) Low power overview of the parabrachial area showing many labeled neurons (arrows) of the parabrachial cell cluster (F, darkfield); (G) shows same section (cresyl violet; brightfield). Scale bars: 100 μm (A), applies to (A,B); 25 μm (C); 500 μm (D), applies to (D,E); 1000 μm (F), applies to (F,G).

Mentions: Subsequently, the distribution of NPS mRNA-expressing cells was determined in more detail on sections dipped in KODAK NTB emulsion. After an 8 week exposure, the radioactive NPS signal was strong, and positive cells were easily recognized both with darkfield and lightfield microscopy in section counterstained with cresyl violet (Figure 3). The distribution of NPS mRNA-expressing cells was the same in all the three examined brainstems.


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)

NPS mRNA-positive neurons in human pons (emulsion-dipped). (A,B) Labeled neurons (arrows) are seen in the periventricular cell cluster in the same section (A, brightfield, cresyl violet; B, darkfield). (C) High magnification showing one NPS mRNA-positive neuron (cresyl violet, brightfield). (D,E) Low power overview of the central pontine gray matter showing a few cells (arrow) in the periventricular NPS cell cluster (D, darkfield); (E) shows the same section (cresyl violet, brightfield). The posterodorsal tegmantal nucleus (PDTg) is surrounded by dashed line in (D,E). (F,G) Low power overview of the parabrachial area showing many labeled neurons (arrows) of the parabrachial cell cluster (F, darkfield); (G) shows same section (cresyl violet; brightfield). Scale bars: 100 μm (A), applies to (A,B); 25 μm (C); 500 μm (D), applies to (D,E); 1000 μm (F), applies to (F,G).
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Related In: Results  -  Collection

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Figure 3: NPS mRNA-positive neurons in human pons (emulsion-dipped). (A,B) Labeled neurons (arrows) are seen in the periventricular cell cluster in the same section (A, brightfield, cresyl violet; B, darkfield). (C) High magnification showing one NPS mRNA-positive neuron (cresyl violet, brightfield). (D,E) Low power overview of the central pontine gray matter showing a few cells (arrow) in the periventricular NPS cell cluster (D, darkfield); (E) shows the same section (cresyl violet, brightfield). The posterodorsal tegmantal nucleus (PDTg) is surrounded by dashed line in (D,E). (F,G) Low power overview of the parabrachial area showing many labeled neurons (arrows) of the parabrachial cell cluster (F, darkfield); (G) shows same section (cresyl violet; brightfield). Scale bars: 100 μm (A), applies to (A,B); 25 μm (C); 500 μm (D), applies to (D,E); 1000 μm (F), applies to (F,G).
Mentions: Subsequently, the distribution of NPS mRNA-expressing cells was determined in more detail on sections dipped in KODAK NTB emulsion. After an 8 week exposure, the radioactive NPS signal was strong, and positive cells were easily recognized both with darkfield and lightfield microscopy in section counterstained with cresyl violet (Figure 3). The distribution of NPS mRNA-expressing cells was the same in all the three examined brainstems.

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.