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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.


Purification of PCR fragments of hNPS and hNPSR1 on agarose gel. Purified PCR fragments of human NPS and NPSR1 were run on 1% agarose gel to confirm size and purity. These fragments were subcloned into TOPO-TA vector (Life Technologies) and, after verification of the sequence, RNA probes were generated. The lanes represent the O'GeneRuler 1 kb Plus DNA Ladder (Fermentas; left), the 183 bp PCR product of human NPS (middle, indicated with “1”) and the 300 bp fragment of human NPSR1 (right, indicated with “2”).
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Figure 1: Purification of PCR fragments of hNPS and hNPSR1 on agarose gel. Purified PCR fragments of human NPS and NPSR1 were run on 1% agarose gel to confirm size and purity. These fragments were subcloned into TOPO-TA vector (Life Technologies) and, after verification of the sequence, RNA probes were generated. The lanes represent the O'GeneRuler 1 kb Plus DNA Ladder (Fermentas; left), the 183 bp PCR product of human NPS (middle, indicated with “1”) and the 300 bp fragment of human NPSR1 (right, indicated with “2”).

Mentions: In order to determine the distribution of NPS mRNA-expressing neuronal populations in the human brainstem, we first produced riboprobes against human NPS (Figure 1). Then, we systematically cut three human brainstems approximately at the level of LC - DR which, based on previous rodent studies (Xu et al., 2007; Clark et al., 2011), is the expected localization of the NPS-expressing neurons.


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)

Purification of PCR fragments of hNPS and hNPSR1 on agarose gel. Purified PCR fragments of human NPS and NPSR1 were run on 1% agarose gel to confirm size and purity. These fragments were subcloned into TOPO-TA vector (Life Technologies) and, after verification of the sequence, RNA probes were generated. The lanes represent the O'GeneRuler 1 kb Plus DNA Ladder (Fermentas; left), the 183 bp PCR product of human NPS (middle, indicated with “1”) and the 300 bp fragment of human NPSR1 (right, indicated with “2”).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Purification of PCR fragments of hNPS and hNPSR1 on agarose gel. Purified PCR fragments of human NPS and NPSR1 were run on 1% agarose gel to confirm size and purity. These fragments were subcloned into TOPO-TA vector (Life Technologies) and, after verification of the sequence, RNA probes were generated. The lanes represent the O'GeneRuler 1 kb Plus DNA Ladder (Fermentas; left), the 183 bp PCR product of human NPS (middle, indicated with “1”) and the 300 bp fragment of human NPSR1 (right, indicated with “2”).
Mentions: In order to determine the distribution of NPS mRNA-expressing neuronal populations in the human brainstem, we first produced riboprobes against human NPS (Figure 1). Then, we systematically cut three human brainstems approximately at the level of LC - DR which, based on previous rodent studies (Xu et al., 2007; Clark et al., 2011), is the expected localization of the NPS-expressing neurons.

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.