PACAP induces spine morphogenesis and synaptic function via miRNA upregulation.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Osaka University
• Principal Investigator: HAYATA ATSUKO 大阪大学, 連合小児発達学研究科, 助教 (70390812)
• Research Collaborator: HASHIMOTO Hitoshi 大阪大学, 大学院薬学研究科, 教授 (30240849) ; NAKAZAWA Takanobu 大阪大学, 大学院歯学研究科, 准教授 (00447335)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: PACAP / 統合失調症 / miRNA / 樹状突起スパイン

Outline of Final Research Achievements

In this study, we showed that PACAP significantly increased the number of PSD-95-positive spines with juxtapositioned synaptophysin-positive presynaptic terminals. We also showed that PACAP significantly increased the biotinylated NR1 and NR2B in the primary cultured hippocampal neurons, suggesting that surface expression of the NMDA receptor is increased by PACAP. On the other hand, we found that the density of PSD-95- positive spines with juxtapositioned synaptophysin-positive presynaptic terminals was significantly low in the primary cultured hippocampal neurons from PACAP deficient mice compared with WT mice.
Furthermore, viral miR-132 overexpression reversed the reduction in the CA1 region of hippocampal spinal density in the PACAP deficient mice. These results indicate that PACAP signaling plays a critical role in spine morphogenesis possibly via miR-132.

Free Research Field

神経分子薬理学

Academic Significance and Societal Importance of the Research Achievements

これらの成果は，統合失調症様の精神行動異常を示すPACAP欠損マウスにおける海馬CA1でのスパインの数の低下が，特定のmiRNAにより改善することを示唆するものであり，統合失調症の病態メカニズムにつながるものであると考えられる．本研究は統合失調症の治療にむけた創薬のための基礎データを提供できるという点からも重要である．