Studies on the involvement of brain adrenergic receptors in oral dyskinesia

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K10124
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Nihon University
• Principal Investigator: AONO Yuri 日本大学, 松戸歯学部, 助教 (50508497)
• Co-Investigator(Kenkyū-buntansha): 三枝 禎 日本大学, 松戸歯学部, 教授 (50277456)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脳微小透析法 / 側坐核 / ラット / GABA

Outline of Final Research Achievements

We have been studying the mechanisms that control acetylcholine (ACh) neural activity in the brain, as they may constitute part of the basis for repetitive abnormal behaviors, including oral dyskinesia-like jaw movements. In the present study, we focused on ACh neural activity in the nucleus accumbens (NAc), a terminal area of the mesolimbic dopaminergic (DAergic) system. We analyzed the involvements of alpha2 adrenergic receptors in regulating the neuronal release of accumbal ACh in rats, as the NAc receives noradrenergic projections. We also studied the roles of GABA transporter subtypes in regulating accumbal extracellular GABA levels, as GABA and ACh neurons may interact in the NAc. Additionally, we analyzed the effects of lipopolysaccharides from P. gingivalis, known to be involved in the progression of periodontal disease, on novel-environment-induced locomotion in mice, which is known to be induced by increased mesolimbic DAergic activity.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

中脳辺縁系DA神経の投射領域の側坐核では，α1ではなくα2受容体刺激により同部位のACh神経活動が低下することが報告できた。つまりノルアドレナリン神経との相互作用の面から脳内のACh神経活動の制御機構について検討ができた。側坐核の基礎的な細胞外GABA量の制御へのGAT-1の関与を示す解析結果が得られた。また新環境でのマウスの活動亢進はE. coliとは異なり，P. gingivalis由来のリポ多糖の全身投与による顕著な影響は受けないことが示された。