論文

査読有り
2023年10月10日

Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke

Proceedings of the National Academy of Sciences
  • Takashi Irie
  • ,
  • Taito Matsuda
  • ,
  • Yoshinori Hayashi
  • ,
  • Kanae Matsuda-Ito
  • ,
  • Akihide Kamiya
  • ,
  • Takahiro Masuda
  • ,
  • Marco Prinz
  • ,
  • Noriko Isobe
  • ,
  • Jun-ichi Kira
  • ,
  • Kinichi Nakashima

120
42
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.2307972120
出版者・発行元
Proceedings of the National Academy of Sciences

Although generating new neurons in the ischemic injured brain would be an ideal approach to replenish the lost neurons for repairing the damage, the adult mammalian brain retains only limited neurogenic capability. Here, we show that direct conversion of microglia/macrophages into neurons in the brain has great potential as a therapeutic strategy for ischemic brain injury. After transient middle cerebral artery occlusion in adult mice, microglia/macrophages converge at the lesion core of the striatum, where neuronal loss is prominent. Targeted expression of a neurogenic transcription factor, NeuroD1, in microglia/macrophages in the injured striatum enables their conversion into induced neuronal cells that functionally integrate into the existing neuronal circuits. Furthermore, NeuroD1-mediated induced neuronal cell generation significantly improves neurological function in the mouse stroke model, and ablation of these cells abolishes the gained functional recovery. Our findings thus demonstrate that neuronal conversion contributes directly to functional recovery after stroke.

リンク情報
DOI
https://doi.org/10.1073/pnas.2307972120
URL
https://pnas.org/doi/pdf/10.1073/pnas.2307972120
ID情報
  • DOI : 10.1073/pnas.2307972120
  • ISSN : 0027-8424
  • eISSN : 1091-6490

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