Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus
The cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp)...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8916 |
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| author | Yuta Madokoro Daisuke Kato Yo Tsuda Itsumi Arakawa Kengo Suzuki Toyohiro Sato Masayuki Mizuno Yuto Uchida Kosei Ojika Noriyuki Matsukawa |
| author_facet | Yuta Madokoro Daisuke Kato Yo Tsuda Itsumi Arakawa Kengo Suzuki Toyohiro Sato Masayuki Mizuno Yuto Uchida Kosei Ojika Noriyuki Matsukawa |
| author_sort | Yuta Madokoro |
| collection | DOAJ |
| description | The cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp) conditional knockout (cKO). Chemically synthesized HCNP or a vehicle were continuously administered into the cerebral ventricle of HCNP-pp cKO mice and littermate floxed (control) mice for two weeks via osmotic pumps. We immunohistochemically measured the cholinergic axon volume in the stratum oriens and functionally evaluated the local field potential in the CA1. Furthermore, choline acetyltransferase (ChAT) and nerve growth factor (NGF) receptor (TrkA and p75NTR) abundances were quantified in wild-type (WT) mice administered HCNP or the vehicle. As a result, HCNP administration morphologically increased the cholinergic axonal volume and electrophysiological theta power in HCNP-pp cKO and control mice. Following the administration of HCNP to WT mice, TrkA and p75NTR levels also decreased significantly. These data suggest that extrinsic HCNP may compensate for the reduced cholinergic axonal volume and theta power in HCNP-pp cKO mice. HCNP may function complementarily to NGF in the cholinergic network in vivo. HCNP may represent a therapeutic candidate for neurological diseases with cholinergic dysfunction, e.g., Alzheimer’s disease and Lewy body dementia. |
| first_indexed | 2024-03-11T03:39:31Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:39:31Z |
| publishDate | 2023-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6389e5ae82c948b09dd2285fb5e137282023-11-18T01:44:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410891610.3390/ijms24108916Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the HippocampusYuta Madokoro0Daisuke Kato1Yo Tsuda2Itsumi Arakawa3Kengo Suzuki4Toyohiro Sato5Masayuki Mizuno6Yuto Uchida7Kosei Ojika8Noriyuki Matsukawa9Department of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanDepartment of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, JapanThe cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp) conditional knockout (cKO). Chemically synthesized HCNP or a vehicle were continuously administered into the cerebral ventricle of HCNP-pp cKO mice and littermate floxed (control) mice for two weeks via osmotic pumps. We immunohistochemically measured the cholinergic axon volume in the stratum oriens and functionally evaluated the local field potential in the CA1. Furthermore, choline acetyltransferase (ChAT) and nerve growth factor (NGF) receptor (TrkA and p75NTR) abundances were quantified in wild-type (WT) mice administered HCNP or the vehicle. As a result, HCNP administration morphologically increased the cholinergic axonal volume and electrophysiological theta power in HCNP-pp cKO and control mice. Following the administration of HCNP to WT mice, TrkA and p75NTR levels also decreased significantly. These data suggest that extrinsic HCNP may compensate for the reduced cholinergic axonal volume and theta power in HCNP-pp cKO mice. HCNP may function complementarily to NGF in the cholinergic network in vivo. HCNP may represent a therapeutic candidate for neurological diseases with cholinergic dysfunction, e.g., Alzheimer’s disease and Lewy body dementia.https://www.mdpi.com/1422-0067/24/10/8916hippocampal cholinergic neurostimulating peptidehippocampal cholinergic neurostimulating peptide precursor proteinhippocampal HCNP-pp conditional KO mouse modelcholine acetyltransferaselocal field potentialtheta oscillation |
| spellingShingle | Yuta Madokoro Daisuke Kato Yo Tsuda Itsumi Arakawa Kengo Suzuki Toyohiro Sato Masayuki Mizuno Yuto Uchida Kosei Ojika Noriyuki Matsukawa Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus International Journal of Molecular Sciences hippocampal cholinergic neurostimulating peptide hippocampal cholinergic neurostimulating peptide precursor protein hippocampal HCNP-pp conditional KO mouse model choline acetyltransferase local field potential theta oscillation |
| title | Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus |
| title_full | Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus |
| title_fullStr | Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus |
| title_full_unstemmed | Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus |
| title_short | Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus |
| title_sort | direct enhancement effect of hippocampal cholinergic neurostimulating peptide on cholinergic activity in the hippocampus |
| topic | hippocampal cholinergic neurostimulating peptide hippocampal cholinergic neurostimulating peptide precursor protein hippocampal HCNP-pp conditional KO mouse model choline acetyltransferase local field potential theta oscillation |
| url | https://www.mdpi.com/1422-0067/24/10/8916 |
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