Wide-field Ca imaging and trans-omics for mouse model of Lewy body disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19443
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Nagoya University
• Principal Investigator: Katsuno Masahisa 名古屋大学, 医学系研究科, 教授 (50402566)
• Co-Investigator(Kenkyū-buntansha): 井口 洋平 名古屋大学, 医学部附属病院, 助教 (80790659) ; 横井 聡 名古屋大学, 医学系研究科, 特任助教 (30815460)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: α-シヌクレイン / パーキンソン病 / レビー小体型認知症 / 幻視 / 神経活動

Outline of Final Research Achievements

We analyzed the pathomechanism of visual cognition impairment in a mouse model of synucleinopathy. After 1 month of α-synuclein administration to the right olfactory bulb, no obvious change was observed in the visual cliff test, but at 3 months, the time spent at the shallow side was prolonged in the α-synuclein group. On the other hand, α-synuclein-treated mice in the substantia nigra showed no abnormalities in behavioral analysis at 1 month and 3 months post-treatment. Neuronal activity in each region was evaluated using c-fos antibody, a marker of neuronal activity. In the lateral olfactory cortex, where synuclein is expressed, the ratio of c-fos-positive cells increased compared to the contralateral area, suggesting that neural activity may be altered in this area. In the visual cortex, the proportion of c-fos-positive cells increased in both the shallow and deep layers on the synuclein-treated side, suggesting a possible change in neural activity.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

嗅内野や嗅周野は嗅覚・聴覚・視覚・体性感覚などが高次感覚連合野で処理される際の経路にあり、海馬との結合も強くエピソード記憶の形成にも重要な部位である。また視覚野は視覚情報を真っ先に処理する部位でもある。今回の研究結果から、シヌクレインが嗅内野・嗅周野まで広がることで視覚野や嗅内野の神経活動に変化が生じ、視覚情報処理そのものに問題が生じる、あるいは視覚情報の伝達に問題が生じることで高次感覚野での視覚情報認知に障害を起こしたのではないかと考えられる。