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Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke

Cell replacement therapy using neural progenitor cells (NPCs) has been shown to be an effective treatment for ischemic stroke. However, the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after ischemia. Microenvironmental acidosis is a common imb...

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Autores principales: Ge, Hongfei, Zhou, Tengyuan, Zhang, Chao, Cun, Yupeng, Chen, Weixiang, Yang, Yang, Zhang, Qian, Li, Huanhuan, Zhong, Jun, Zhang, Xuyang, Feng, Hua, Hu, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAAS 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234266/
https://www.ncbi.nlm.nih.gov/pubmed/37275123
http://dx.doi.org/10.34133/research.0105
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author Ge, Hongfei
Zhou, Tengyuan
Zhang, Chao
Cun, Yupeng
Chen, Weixiang
Yang, Yang
Zhang, Qian
Li, Huanhuan
Zhong, Jun
Zhang, Xuyang
Feng, Hua
Hu, Rong
author_facet Ge, Hongfei
Zhou, Tengyuan
Zhang, Chao
Cun, Yupeng
Chen, Weixiang
Yang, Yang
Zhang, Qian
Li, Huanhuan
Zhong, Jun
Zhang, Xuyang
Feng, Hua
Hu, Rong
author_sort Ge, Hongfei
collection PubMed
description Cell replacement therapy using neural progenitor cells (NPCs) has been shown to be an effective treatment for ischemic stroke. However, the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after ischemia. Microenvironmental acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a (ASIC1a), a subunit of proton-gated cation channels following ischemic stroke. However, the role of ASIC1a in NPCs post-ischemia remains elusive. Here, our results indicated that ASIC1a was expressed in NPCs with channel functionality, which could be activated by extracellular acidification. Further evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation, which could be primarily reversed by pharmacological or genetic disruption of ASIC1a. In vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke. Subsequently, ASIC1a gain of function partially abrogated this effect. Moreover, the administration of ASIC1a antagonists (amiloride or Psalmotoxin 1) promoted functional recovery by enhancing NPC migration and neurogenesis. Together, these results demonstrate targeting ASIC1a is a novel strategy potentiating NPC migration toward penumbra to repair lesions following ischemic stroke and even for other neurological diseases with the presence of niche acidosis.
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spelling pubmed-102342662023-06-02 Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke Ge, Hongfei Zhou, Tengyuan Zhang, Chao Cun, Yupeng Chen, Weixiang Yang, Yang Zhang, Qian Li, Huanhuan Zhong, Jun Zhang, Xuyang Feng, Hua Hu, Rong Research (Wash D C) Research Article Cell replacement therapy using neural progenitor cells (NPCs) has been shown to be an effective treatment for ischemic stroke. However, the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after ischemia. Microenvironmental acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a (ASIC1a), a subunit of proton-gated cation channels following ischemic stroke. However, the role of ASIC1a in NPCs post-ischemia remains elusive. Here, our results indicated that ASIC1a was expressed in NPCs with channel functionality, which could be activated by extracellular acidification. Further evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation, which could be primarily reversed by pharmacological or genetic disruption of ASIC1a. In vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke. Subsequently, ASIC1a gain of function partially abrogated this effect. Moreover, the administration of ASIC1a antagonists (amiloride or Psalmotoxin 1) promoted functional recovery by enhancing NPC migration and neurogenesis. Together, these results demonstrate targeting ASIC1a is a novel strategy potentiating NPC migration toward penumbra to repair lesions following ischemic stroke and even for other neurological diseases with the presence of niche acidosis. AAAS 2023-06-01 /pmc/articles/PMC10234266/ /pubmed/37275123 http://dx.doi.org/10.34133/research.0105 Text en Copyright © 2023 Hongfei Ge et al. https://creativecommons.org/licenses/by/4.0/Exclusive licensee Science and Technology Review Publishing House. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Ge, Hongfei
Zhou, Tengyuan
Zhang, Chao
Cun, Yupeng
Chen, Weixiang
Yang, Yang
Zhang, Qian
Li, Huanhuan
Zhong, Jun
Zhang, Xuyang
Feng, Hua
Hu, Rong
Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke
title Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke
title_full Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke
title_fullStr Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke
title_full_unstemmed Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke
title_short Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke
title_sort targeting asic1a promotes neural progenitor cell migration and neurogenesis in ischemic stroke
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234266/
https://www.ncbi.nlm.nih.gov/pubmed/37275123
http://dx.doi.org/10.34133/research.0105
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