Hippocampal Cholinergic Neurostimulating Peptide as a Possible Modulating Factor against Glutamatergic Neuronal Disability by Amyloid Oligomers.
Hippocampal Cholinergic Neurostimulating Peptide as a Possible Modulating Factor against Glutamatergic Neuronal Disability by Amyloid Oligomers.
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DOI：
10.1177/0963689717721232
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发表时间：
2017-09
影响因子：
3.3
通讯作者：
Matsukawa N
中科院分区：
文献类型：
--
作者：
Sato T;Ohi Y;Kato D;Mizuno M;Takase H;Kanamori T;Borlongan CV;Haji A;Matsukawa N
尽管大脑出现与阿尔茨海默病 (AD) 相关的病理变化，但一些患者仍保留了认知功能。最近的一项流行病学研究表明，饮食、运动、认知训练和血管风险监测干预措施可能会减少普通人群中高危老年人的认知能力下降。然而，这种认知功能保存背后的分子机制的细节仍然未知。先前的报告表明，当合成淀粉样蛋白-β (Aβ) 寡聚物不完全抑制海马长时程增强 (LTP) 时，丰富的环境可通过 β2 肾上腺素能信号防止海马长时程增强 (LTP) 受损。来自内侧间隔核（MSN）的胆碱能网络也是通过烟碱能和/或毒蕈碱能乙酰胆碱受体激活海马谷氨酸神经的主要调节系统。之前，我们报道了 MSN 中胆碱能调节基因海马胆碱能神经刺激肽（HCNP）的重要性。通过使用小鼠海马切片，我们证明了 MSN 的胆碱能神经激活增强了不饱和 LTP 期间的谷氨酸能神经元活性，但在饱和 LTP 期间则不然。合成的 Aβ 寡聚体以浓度依赖性方式抑制海马谷氨酸能活性。此外，HCNP 以及通过毒蕈碱 M1 受体发挥作用的胆碱能激动剂，可防止合成 Aβ 寡聚物诱导的海马谷氨酸神经元活动受到抑制。这一结果表明，持续的胆碱能激活可能是 AD 病理变化认知影响个体差异的潜在解释。
Despite having pathological changes in the brain associated with Alzheimer's disease (AD), some patients have preserved cognitive function. A recent epidemiological study has shown that diet, exercise, cognitive training, and vascular risk monitoring interventions may reduce cognitive decline in at-risk elderly people in the general population. However, the details of molecular mechanisms underlying this cognitive function preservation are still unknown. Previous reports have demonstrated that enriched environments prevent the impairment of hippocampal long-term potentiation (LTP) through β2-adrenergic signals, when LTP is incompletely suppressed by synthetic amyloid-β (Aβ) oligomers. The cholinergic network from the medial septal nucleus (MSN) is also a main modulating system for hippocampal glutamatergic neural activation through nicotinergic and/or muscarinergic acetylcholine receptors. Previously, we reported the importance of a cholinergic regulator gene in the MSN, hippocampal cholinergic neurostimulating peptide (HCNP). By using hippocampal sections from mice, we here demonstrated that the cholinergic neural activation from the MSN enhanced the glutamatergic neuronal activity during unsaturated LTP but not during saturated LTP. Synthetic Aβ oligomers suppressed the hippocampal glutamatergic activity in a concentration-dependent manner. Furthermore, HCNP, as well as a cholinergic agonist acting through the muscarinic M1 receptor, prevented the suppression of hippocampal glutamatergic neuronal activity induced by synthetic Aβ oligomers. This result suggests that the persisting cholinergic activation might be a potential explanation for the individual differences in cognitive effects of AD pathological changes.
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影响因子：
16.2
作者：
Li S;Jin M;Zhang D;Yang T;Koeglsperger T;Fu H;Selkoe DJ
通讯作者：
Selkoe DJ
影响因子：
4.7
作者：
Bherer L;Erickson KI;Liu-Ambrose T
通讯作者：
Liu-Ambrose T
影响因子：
16.2
作者：
Gu Z;Yakel JL
通讯作者：
Yakel JL
DOI：
10.2174/1871527313666140711093858
发表时间：
2014-01-01
影响因子：
3
作者：
Schneider, Andrew R.;Sari, Youssef
通讯作者：
Sari, Youssef
影响因子：
2.9
作者：
OJIKA, K;KOJIMA, S;YAMAMOTO, M
通讯作者：
YAMAMOTO, M