The resolution of molecular mechanism on connitive reserve by HCNP function

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HCNP / コリン作動性神経 / 認知機能障害 / 認知予備能 / ＨＣＮＰ / 海馬神経活動 / acetylcholine / hippocampus / A beta / Aβオリゴマー

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.

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。

Research Products

• [Journal Article] Corticobasal syndrome-Pick's disease: A clinicopathological study (2020)
  • Author(s): Uchida Y, Yoshida M, Takada K, Tsugu Y, Ueki Y, Matsukawa N.
  • Journal Title: J Neurol Sci Volume: 412 Pages: 116752-116752
  • DOI: 10.1016/j.jns.2020.116752
  • Peer Reviewed
• [Journal Article] Correlating diffusion-weighted MRI intensity with type 2 pathology in mixed MM-type sporadic Creutzfeldt-Jakob disease. (2020)
  • Author(s): Ikeda T, Iwasaki Y, Sakurai K, Akagi A, Riku Y, Mimuro M, Miyahara H, Kitamoto T, Matsukawa N, Yoshida M.
  • Journal Title: J Neurol Sci. Volume: 408 Pages: 116515-116515
  • DOI: 10.1016/j.jns.2019.116515
  • Peer Reviewed
• [Journal Article] Reduced Cholinergic Activity in the Hippocampus of Hippocampal Cholinergic Neurostimulating Peptide Precursor Protein Knockout Mice. (2019)
  • Author(s): Madokoro Y, Yoshino Y, Kato D, Sato T, Mizuno M, Kanamori T, Shimazawa M, Hida H, Hara H, Yoshida M, Borlongan CV, Ojika K, Matsukawa N.
  • Journal Title: Int J Mol Sci. Volume: 20(21) Issue: 21 Pages: 1-17
  • DOI: 10.3390/ijms20215367
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anatomical Links between White Matter Hyperintensity and Medial Temporal Atrophy Reveal Impairment of Executive Functions. (2019)
  • Author(s): Yamanaka T, Uchida Y, Sakurai K, Kato D, Mizuno M, Sato T, Madokoro Y, Kondo Y, Suzuki A, Ueki Y, Ishii F, Borlongan CV, Matsukawa N
  • Journal Title: Aging Dis. Volume: 10(4) Issue: 4 Pages: 711-718
  • DOI: 10.14336/ad.2018.0929
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nigrostriatal Dopaminergic Dysfunction And Altered Functional Connectivity In REM Sleep Behaviour Disorder With Mild Motor Impairment (2019)
  • Author(s): Yamada G, Ueki Y, Oishi N, Oguri T, Fukui A, Nakayama M, Kandori A, Sano Y, Kan H, Arai N, Sakurai K, Wada I, Matsukawa N
  • Journal Title: Front. Neurol. Volume: 10 Pages: 802-802
  • DOI: 10.3389/fneur.2019.00802
  • Peer Reviewed / Open Access
• [Journal Article] Hippocampal Cholinergic Neurostimulating Peptide as a Possible Modulating Factor against Glutamatergic Neuronal Disability by Amyloid Oligomers. (2017)
  • Author(s): Sato T, Ohi Y, Kato D, Mizuno M, Takase H, Kanamori T, Borlongan CV, Haji A, Matsukawa N
  • Journal Title: Cell transplantation Volume: 26 Issue: 9 Pages: 1542-1550
  • DOI: 10.1177/0963689717721232
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Patent(Industrial Property Rights)] 遺伝子改変非ヒト動物及びその作製方法 (2019)
  • Inventor(s): 松川則之
  • Industrial Property Rights Holder: 松川則之
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2019-084543
  • Filing Date: 2019