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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.


Quantitative evaluation of NPS mRNA-positive neurons in the human pons. Stereological methods show that the by far highest number of NPS cells is located in the parabrachial region. Data expressed by mean ±S.E.M; N = 3.
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Figure 6: Quantitative evaluation of NPS mRNA-positive neurons in the human pons. Stereological methods show that the by far highest number of NPS cells is located in the parabrachial region. Data expressed by mean ±S.E.M; N = 3.

Mentions: Based on stereological methods, the total number of NPS mRNA-expressing cells was estimated to approximately 22 thousands bilaterally (22,317 ± 2411, altogether in both sides). The vast majority (84%) of labeled cells were located in the PB cluster (Figure 6). It is of note that we observed some inter-individual variability in the number of cells (estimated number of NPS mRNA-expressing neurons in the peri-ventricular cluster: 3650, 2150, 1750, cases 1–3, respectively; peri-coerulear cells: 1050, 450, 1700, cases 1–3, respectively; parabrachial cluster: 21,000, 15,050, 20,150, cases 1–3, respectively). Despite this variability, the proportional distribution of NPS cells was apparently different in human subjects, compared to the situation previously described in rodents (Liu et al., 2011). The most prominent difference was that the human peri-coerulear area showed only a few scattered NPS cells in human (ca 5% of all counted neurons), while the peri-coerulear NPS neurons form a prominent cluster in rodents (ca 30% of all counted neurons in mouse; Liu et al., 2011).


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)

Quantitative evaluation of NPS mRNA-positive neurons in the human pons. Stereological methods show that the by far highest number of NPS cells is located in the parabrachial region. Data expressed by mean ±S.E.M; N = 3.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585187&req=5

Figure 6: Quantitative evaluation of NPS mRNA-positive neurons in the human pons. Stereological methods show that the by far highest number of NPS cells is located in the parabrachial region. Data expressed by mean ±S.E.M; N = 3.
Mentions: Based on stereological methods, the total number of NPS mRNA-expressing cells was estimated to approximately 22 thousands bilaterally (22,317 ± 2411, altogether in both sides). The vast majority (84%) of labeled cells were located in the PB cluster (Figure 6). It is of note that we observed some inter-individual variability in the number of cells (estimated number of NPS mRNA-expressing neurons in the peri-ventricular cluster: 3650, 2150, 1750, cases 1–3, respectively; peri-coerulear cells: 1050, 450, 1700, cases 1–3, respectively; parabrachial cluster: 21,000, 15,050, 20,150, cases 1–3, respectively). Despite this variability, the proportional distribution of NPS cells was apparently different in human subjects, compared to the situation previously described in rodents (Liu et al., 2011). The most prominent difference was that the human peri-coerulear area showed only a few scattered NPS cells in human (ca 5% of all counted neurons), while the peri-coerulear NPS neurons form a prominent cluster in rodents (ca 30% of all counted neurons in mouse; Liu et al., 2011).

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.