Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice
Abstract Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer’s disease. The aim of the present study was to elucidate the relationship between glutamatergic neural functional decline and cholinergic neural dysfunction in the hip...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-23846-x |
| _version_ | 1811230473252241408 |
|---|---|
| author | Kengo Suzuki Yoshiaki Ohi Toyohiro Sato Yo Tsuda Yuta Madokoro Masayuki Mizuno Kenichi Adachi Yuto Uchida Akira Haji Kosei Ojika Noriyuki Matsukawa |
| author_facet | Kengo Suzuki Yoshiaki Ohi Toyohiro Sato Yo Tsuda Yuta Madokoro Masayuki Mizuno Kenichi Adachi Yuto Uchida Akira Haji Kosei Ojika Noriyuki Matsukawa |
| author_sort | Kengo Suzuki |
| collection | DOAJ |
| description | Abstract Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer’s disease. The aim of the present study was to elucidate the relationship between glutamatergic neural functional decline and cholinergic neural dysfunction in the hippocampus. We report the importance of hippocampal cholinergic neurostimulating peptide (HCNP) in inducing acetylcholine synthesis in the medial septal nucleus. Here, we demonstrate that HCNP-precursor protein (pp) knockout (KO) mice electrophysiologically presented with glutamatergic dysfunction in the hippocampus with age. The impairment of cholinergic function via a decrease in vesicular acetylcholine transporter in the pre-synapse with reactive upregulation of the muscarinic M1 receptor may be partly involved in glutamatergic dysfunction in the hippocampus of HCNP-pp KO mice. The results, in combination with our previous reports that show the reduction of hippocampal theta power through a decrease of a region-specific choline acetyltransferase in the stratum oriens of CA1 and the decrease of acetylcholine concentration in the hippocampus, may indicate the defined cholinergic dysfunction in HCNP-pp KO mice. This may also support that HCNP-pp KO mice are appropriate genetic models for cholinergic functional impairment in septo-hippocampal interactions. Therefore, according to the cholinergic hypothesis, the model mice might are potential partial pathological animal models for Alzheimer’s disease. |
| first_indexed | 2024-04-12T10:29:53Z |
| format | Article |
| id | doaj.art-f0d111b92de54a0c9d61c73a4666cc42 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T10:29:53Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f0d111b92de54a0c9d61c73a4666cc422022-12-22T03:36:53ZengNature PortfolioScientific Reports2045-23222022-11-0112111010.1038/s41598-022-23846-xReduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout miceKengo Suzuki0Yoshiaki Ohi1Toyohiro Sato2Yo Tsuda3Yuta Madokoro4Masayuki Mizuno5Kenichi Adachi6Yuto Uchida7Akira Haji8Kosei Ojika9Noriyuki Matsukawa10Department of Neurology, Graduate School of Medical Sciences, Nagoya City UniversityLaboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin UniversityDepartment of Neurology, Graduate School of Medical Sciences, Nagoya City UniversityDepartment of Neurology, Graduate School of Medical Sciences, Nagoya City UniversityDepartment of Neurology, Graduate School of Medical Sciences, Nagoya City UniversityDepartment of Neurology, Graduate School of Medical Sciences, Nagoya City UniversityDepartment of Neurology, Graduate School of Medical Sciences, Nagoya City UniversityDepartment of Neurology, Graduate School of Medical Sciences, Nagoya City UniversityLaboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin UniversityDepartment of Neurology, Graduate School of Medical Sciences, Nagoya City UniversityDepartment of Neurology, Graduate School of Medical Sciences, Nagoya City UniversityAbstract Cholinergic activation can enhance glutamatergic activity in the hippocampus under pathologic conditions, such as Alzheimer’s disease. The aim of the present study was to elucidate the relationship between glutamatergic neural functional decline and cholinergic neural dysfunction in the hippocampus. We report the importance of hippocampal cholinergic neurostimulating peptide (HCNP) in inducing acetylcholine synthesis in the medial septal nucleus. Here, we demonstrate that HCNP-precursor protein (pp) knockout (KO) mice electrophysiologically presented with glutamatergic dysfunction in the hippocampus with age. The impairment of cholinergic function via a decrease in vesicular acetylcholine transporter in the pre-synapse with reactive upregulation of the muscarinic M1 receptor may be partly involved in glutamatergic dysfunction in the hippocampus of HCNP-pp KO mice. The results, in combination with our previous reports that show the reduction of hippocampal theta power through a decrease of a region-specific choline acetyltransferase in the stratum oriens of CA1 and the decrease of acetylcholine concentration in the hippocampus, may indicate the defined cholinergic dysfunction in HCNP-pp KO mice. This may also support that HCNP-pp KO mice are appropriate genetic models for cholinergic functional impairment in septo-hippocampal interactions. Therefore, according to the cholinergic hypothesis, the model mice might are potential partial pathological animal models for Alzheimer’s disease.https://doi.org/10.1038/s41598-022-23846-x |
| spellingShingle | Kengo Suzuki Yoshiaki Ohi Toyohiro Sato Yo Tsuda Yuta Madokoro Masayuki Mizuno Kenichi Adachi Yuto Uchida Akira Haji Kosei Ojika Noriyuki Matsukawa Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice Scientific Reports |
| title | Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice |
| title_full | Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice |
| title_fullStr | Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice |
| title_full_unstemmed | Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice |
| title_short | Reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice |
| title_sort | reduction of glutamatergic activity through cholinergic dysfunction in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice |
| url | https://doi.org/10.1038/s41598-022-23846-x |
| work_keys_str_mv | AT kengosuzuki reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT yoshiakiohi reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT toyohirosato reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT yotsuda reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT yutamadokoro reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT masayukimizuno reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT kenichiadachi reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT yutouchida reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT akirahaji reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT koseiojika reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice AT noriyukimatsukawa reductionofglutamatergicactivitythroughcholinergicdysfunctioninthehippocampusofhippocampalcholinergicneurostimulatingpeptideprecursorproteinknockoutmice |