Functional reconstruction of neural circuits using differentiation of astrocytes into neurons

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19425
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 51:Brain sciences and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Tanaka Kohichi 東京医科歯科大学, 難治疾患研究所, 教授 (80171750)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: アストロサイト / 分化転換 / 神経変性疾患

Outline of Final Research Achievements

To treat neurodegenerative diseases, it is necessary not only to replenish lost neurons, but also to allow the replenished neurons to functionally connect with existing neuronal circuits. It has recently been shown that knockdown of the Ptbp1 gene in astrocytes can cause astrocytes to differentiate into cells with the same characteristics as the neurons at that site and integrate into existing neural circuits, but the efficiency of this differentiation is not sufficient. In this study, the Ptbp1 gene was deleted from astrocytes in all regions of the brain, and an in vivo system was developed to analyze the differentiation and conversion ability of astrocytes in each region. However, it was found that deletion of the Ptbp1 gene did not result in differentiation conversion from astrocytes to neurons.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患を治療するためには、失われた神経細胞を補充するのみならず、補充された神経細胞が既存の神経回路と機能的な結合をする必要がある。最近アストロサイトのPtbp1遺伝子をノックダウンすると、アストロサイトがその部位の神経細胞と同じ特徴を持った細胞に分化転換し、既存の神経回路に組み込まれることが示されたが、分化転換の効率は十分ではない。本研究では、アストロサイトから神経細胞への分化転換を阻害する遺伝子を同定し、その効率化を目指した。しかし、Ptbp1遺伝子の欠損ではアストロサイトから神経細胞への分化転換が起こらないことが明らかになった