Glutamatergic neurotransmission and perineuronal nets

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K07344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: International University of Health and Welfare
• Principal Investigator: Mariko Hayashi 国際医療福祉大学, 医学部, 講師 (30525811)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 神経伝達 / グルタミン酸 / アストロサイト / ぺリニューロナルネット / ヒアルロン酸

Outline of Final Research Achievements

Hyaluronan is synthesized, secreted, and anchored by hyaluronan synthases (HAS) at the plasma membrane and comprises the backbone of perineuronal nets around neuronal soma and dendrites. However, the molecular targets of hyaluronan to regulate synaptic transmission in the central nervous system have not been fully identified. We found that hyaluronan is a negative regulator of excitatory signals. Hyaluronan synthesized by HAS supports the activity of glial glutamate transporter 1 (GLT1). GLT1 also retracted from cellular processes of cultured astrocytes after hyaluronidase treatment and hyaluronan synthesis inhibition. A serial knockout study showed that all three HAS subtypes recruit GLT1 to cellular processes. Furthermore, hyaluronidase treatment activated neurons in a dissociated rat hippocampal culture and caused neuronal damage due to excitotoxicity. Our findings reveal that hyaluronan helps to turn off excitatory signals by supporting glutamate clearance.

Free Research Field

神経生物学

Academic Significance and Societal Importance of the Research Achievements

ペリニューロナルネットは神経細胞の興奮と抑制のバランスに関わる。その異常は、集中力の発揮など多くの神経疾患で障害される高次機能に関わるとされるが、神経伝達においてどのような役割を果たしているかは不明であった。ぺリニューロナルネットの骨格をなすヒアルロン酸の合成が、グルタミン酸による伝達をピンポイントに絞ったものにすることを明らかにできたことで、組織病理的に観察される現象と、病態とをつなぐ知見が得られた。