Mechanism of Epidermal growth factor on GABAergic neuronal development via the regulation of perineuronal net

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K06460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Niigata University
• Principal Investigator: IWAKURA Yuriko 新潟大学, 脳研究所, 助教 (40452081)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 上皮成長因子 / 抑制性神経細胞 / ペリニューロナルネット / コンドロイチン硫酸プロテオグリカン

Outline of Final Research Achievements

Epidermal growth factor (EGF) is a classical growth factor widely expressed in the brain with its receptor. We previously reported that EGF inhibits the morphological/functional development of parvalbumin (PV)-positive gamma-aminobutyric acid interneurons in the cortex. PV-positive neurons (PV neurons) are a major subtype of interneurons that often form perineuronal nets (PNNs), which are extracellular matrix structures that cover the cell body and dendrites with the development of PV neurons. In the present study, we investigated the possibility that EGF regulates PNN formation as a contributing factor to EGF’s developmental and functional suppressive effects on PV-positive neurons. The results showed that excessive EGF signaling during development promotes cleavage of CSPG, a major component of PNNs, by increasing proteolytic enzyme (MMP) activity, thereby inhibiting normal PNN construction.

Free Research Field

分子神経生物学、神経生化学

Academic Significance and Societal Importance of the Research Achievements

発達期の抑制性神経細胞の異常は、発達障害や精神疾患の一因となる可能性が議論されている。例えば統合失調症患者の死後脳では、PNNs構造の変化が報告されている。自閉症の発症や病態にもPNNsや細胞外マトリクス調節因子との関連が示唆される。これらの疾患は、発症機序や病態、分子マーカーなど未解明の点が多い。PNNのような細胞外環境とEGFのような栄養因子シグナルの関連性が明らかになることで、このような複雑な疾患の研究に新たな展開をもたらす一端となると考える。