The resolution of molecular mechanism on connitive reserve by HCNP function

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09761
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagoya City University
• Principal Investigator: Matsukawa Noriyuki 名古屋市立大学, 医薬学総合研究院(医学), 教授 (20305543)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: HCNP / コリン作動性神経 / 認知機能障害 / 認知予備能

Outline of Final Research Achievements

The reduction of Hippocampal cholinergic neurostimulating peptide (HCNP) may induce the inhibition of theta oscillation in CA1, and exhibit a diminished cholinergic projection to CA1 and direct decrease of acethylcholine concentration in hippocampus. While synthetic Aβ oligomers suppressed the hippocampal glutamatergic activity in a concentration-dependent manner, HCNP prevents the suppression of hippocampal glutamatergic neuronal activity induced by synthetic Aβ oligomers. To clarify the cholinergic effect on memory impairement in APP gene-mutated model, we achieved to generate a novel model; APP knock-in mice with HCNP knockout, being Alzheimer's model with lower cholinergic function from medial septal nucleus to hippocamps.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

HCNP維持が、海馬神経活動維持に関与する可能性が予定通り示される可能性がある。この結果は、コリン作動性神経活動とアミロイド仮説を介して、認知機能維持（認知予備能）の分子メカニズムの一部が明らかになる可能性がある。創薬における新たな分子標的になる可能性がある。