論文 - 詳細
| RRC ID | 81305 |
|---|---|
| 著者 | Irie T, Matsuda T, Hayashi Y, Matsuda-Ito K, Kamiya A, Masuda T, Prinz M, Isobe N, Kira JI, Nakashima K. |
| タイトル | Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
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. |
| 巻・号 | 120(42) |
| ページ | e2307972120 |
| 公開日 | 2023-10-17 |
| DOI | 10.1073/pnas.2307972120 |
| PMID | 37812721 |
| PMC | PMC10589698 |
| MeSH | Animals Brain / metabolism Brain Ischemia* / metabolism Infarction, Middle Cerebral Artery / metabolism Macrophages / metabolism Mammals Mice Microglia / metabolism Neurons / metabolism Stroke* / metabolism |
| IF | 9.412 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 98 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |