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


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.

SUBMITTER: Irie T 

PROVIDER: S-EPMC10589698 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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

Irie Takashi T   Matsuda Taito T   Hayashi Yoshinori Y   Matsuda-Ito Kanae K   Kamiya Akihide A   Masuda Takahiro T   Prinz Marco M   Isobe Noriko N   Kira Jun-Ichi JI   Nakashima Kinichi K  

Proceedings of the National Academy of Sciences of the United States of America 20231010 42


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 str  ...[more]

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