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Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke.
Wu, Chaoran; Li, Yu; He, Xinran; Sun, Hao; Zhang, Shiwen; Hou, Fengsheng; Hu, Mengqiu; Lan, Aili; Zhang, Hao; Qi, Long; Zhang, Huibin; Liao, Hong.
Afiliación
  • Wu C; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Li Y; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • He X; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Sun H; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Zhang S; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Hou F; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Hu M; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Lan A; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Zhang H; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Qi L; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • Zhang H; Center for Drug Discovery, Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing, China.
  • Liao H; New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Glia ; 72(6): 1150-1164, 2024 06.
Article en En | MEDLINE | ID: mdl-38436489
ABSTRACT
Ischemic stroke is the leading cause of adult disability. The rewiring of surviving neurons is the fundamental process for functional recovery. Accumulating evidence implicates astrocytes in synapses and neural circuits formation, but few studies have further studied how to enhance the effects of astrocytes on synapse and circuits after stroke and its impacts on post-stroke functional recovery. In this study, we made use of chemogenetics to specifically activate astrocytic Gi signaling in the peri-infarcted sensorimotor cortex at different time epochs in a mouse model of photothrombotic stroke. We found that early activation of astrocytic hM4Di after stroke by CNO modulates astrocyte activity and upregulates synaptogenic molecules including thrombospondin-1 (TSP1) as revealed by bulk RNA-sequencing, but no significant improvement was observed in dendritic spine density and behavioral performance in grid walking test. Interestingly, when the manipulation was initiated at the subacute phase of stroke, the recovery of spine density and motor function could be effectively promoted, accompanied by increased TSP1 expression. Our data highlight the important role of astrocytes in synapse remodeling during the repair phase of stroke and suggest astrocytic Gi signaling activation as a potential strategy for synapse regeneration, circuit rewiring, and functional recovery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Astrocitos / Accidente Cerebrovascular Límite: Animals Idioma: En Revista: Glia Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Astrocitos / Accidente Cerebrovascular Límite: Animals Idioma: En Revista: Glia Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos