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海马胆碱能神经刺激肽前体蛋白敲除小鼠海马乙酰胆碱减少。

Reduction of acetylcholine in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice.

机构信息

Department of Neurology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.

Core Laboratory, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.

出版信息

Sci Rep. 2021 Nov 11;11(1):22072. doi: 10.1038/s41598-021-01667-8.

DOI:10.1038/s41598-021-01667-8
PMID:34764402
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8586363/
Abstract

The cholinergic efferent network from the medial septal nucleus to the hippocampus plays an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP), which induces acetylcholine (Ach) synthesis in the medial septal nuclei of an explant culture system, was purified from the soluble fraction of postnatal rat hippocampus. HCNP is processed from the N-terminal region of a 186-amino acid, 21-kDa HCNP precursor protein, also known as Raf kinase inhibitory protein and phosphatidylethanolamine-binding protein 1. Here, we confirmed direct reduction of Ach release in the hippocampus of freely moving HCNP-pp knockout mice under an arousal state by the microdialysis method. The levels of vesicular acetylcholine transporter were also decreased in the hippocampus of these mice in comparison with those in control mice, suggesting there was decreased incorporation of Ach into the synaptic vesicle. These results potently indicate that HCNP may be a cholinergic regulator in the septo-hippocampal network.

摘要

从内侧隔核到海马的胆碱能传出网络在学习和记忆过程中起着重要作用。这种胆碱能投射可以在海马中产生θ振荡,从而对新信息进行编码。海马胆碱能神经刺激肽(HCNP)可在器官培养系统的内侧隔核中诱导乙酰胆碱(Ach)的合成,它是从出生后大鼠海马的可溶性部分中纯化出来的。HCNP 是由一种 186 个氨基酸、21kDa 的 HCNP 前体蛋白的 N 端区域加工而成的,该前体蛋白也被称为 Raf 激酶抑制蛋白和磷脂酰乙醇胺结合蛋白 1。在这里,我们通过微透析法证实,在觉醒状态下,自由活动的 HCNP-pp 敲除小鼠海马中的 Ach 释放直接减少。与对照小鼠相比,这些小鼠海马中的囊泡乙酰胆碱转运体水平也降低,表明 Ach 掺入突触囊泡的减少。这些结果有力地表明,HCNP 可能是隔海马网络中的一种胆碱能调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/85a15ae80d98/41598_2021_1667_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/cdc20d33c64d/41598_2021_1667_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/a7e42fc01f66/41598_2021_1667_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/c616a8d953e3/41598_2021_1667_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/a83333aacd4a/41598_2021_1667_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/85a15ae80d98/41598_2021_1667_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/cdc20d33c64d/41598_2021_1667_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/a7e42fc01f66/41598_2021_1667_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/c616a8d953e3/41598_2021_1667_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/a83333aacd4a/41598_2021_1667_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c23/8586363/85a15ae80d98/41598_2021_1667_Fig5_HTML.jpg

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