hippocampal cholinergic neurostimulating peptide (HCNP), cholinergic modulation, muscarinic receptor, long-term potentiation (LTP), Aβ oligomers, phosphatidylethanolamine-binding protein (PEBP)
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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Citation / Publisher Attribution
Cell Transplantation, v. 26, issue 9, p. 1542-1550
Scholar Commons Citation
Sato, Toyohiro; Ohi, Yoshiaki; Kato, Daisuke; Mizuno, Masayuki; Takase, Hiroshi; Kanamori, Tetsuko; Borlongan, Cesar V.; Haji, Akira; and Matsukawa, Noriyuki, "Hippocampal Cholinergic Neurostimulating Peptide as a Possible Modulating Factor against Glutamatergic Neuronal Disability by Amyloid Oligomers" (2017). Neurosurgery and Brain Repair Faculty Publications. 19.
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