Document Type

Article

Publication Date

2017

Keywords

hippocampal cholinergic neurostimulating peptide (HCNP), cholinergic modulation, muscarinic receptor, long-term potentiation (LTP), Aβ oligomers, phosphatidylethanolamine-binding protein (PEBP)

Abstract

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.

Digital Object Identifier (DOI)

https://doi.org/10.1177/0963689717721232

Rights Information

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Citation / Publisher Attribution

Cell Transplantation, v. 26, issue 9, p. 1542-1550

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