August 9, 2024
University of Yamanashi
Kyushu University
Keio University
The University of Tokyo
A research team led by Professor Shuichi Koizumi and Professor Eiji Shigetomi of the Faculty of Medical Sciences (Pharmacology (Division of), School of Medicine, and Yamanashi GLIA Center), University of Yamanashi, has discovered a glial substance that causes abnormal brain excitation. The experiments for this study were conducted primarily by Professor Eiji Shigetomi and Hideaki Suzuki (then a student in the Department of Medicine, University of Yamanashi). This research was also supported by collaborators including Professor Makoto Tsuda of the Faculty of Pharmaceutical Sciences, Kyushu University; Professor Hiroyuki Kinouchi of the Faculty of Medical Sciences, University of Yamanashi; Professor Kenji Tanaka of the Department of Brain Science, Institute for Advanced Medical Research, School of Medicine, Keio University; and Professor Haruhiko Bito of the Graduate School of Medicine, The University of Tokyo.
It is known that in various brain diseases, the hyperexcitation of neurons leads to their abnormality, loss, and degeneration. The role of glial cells as one of the causes of these changes has been gaining attention. In this study, we have identified "IGFBP2" as a glial substance that causes abnormal brain excitation (neuronal hyperexcitation).
In various brain diseases such as Alzheimer's disease, epilepsy, and stroke, a type of glial cell called "astrocytes" commonly upregulates the expression of P2Y 1 receptors, becoming "disease-associated astrocytes." However, how these astrocytes that highly express P2Y 1 receptors (disease-associated astrocytes) are involved in these brain diseases was largely unknown. In the current study, we created mice with artificial disease-associated astrocytes that were forced to highly express P2Y 1 receptors and found that 1) these disease-associated astrocytes produce and secrete a novel glial substance, IGFBP2, and 2) this substance causes neuronal hyperexcitation. Furthermore, we found that IGFBP2 is highly expressed in disease-associated astrocytes in multiple brain disease models, including actual epilepsy and cerebral infarction models. The findings of this research were published in the online edition of Nature Communications on August 8, 2024 (JST).
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