Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke

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Main Authors: Chaoran Wu, Yu Li, Xinran He, Hao Sun, Shiwen Zhang, Fengsheng Hou, Mengqiu Hu, Aili Lan, Hao Zhang, Long Qi, Huibin Zhang, Hong Liao
Format: Artículo Open Access
Published: Wiley 2024
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author Chaoran Wu
Yu Li
Xinran He
Hao Sun
Shiwen Zhang
Fengsheng Hou
Mengqiu Hu
Aili Lan
Hao Zhang
Long Qi
Huibin Zhang
Hong Liao
author_facet Chaoran Wu
Yu Li
Xinran He
Hao Sun
Shiwen Zhang
Fengsheng Hou
Mengqiu Hu
Aili Lan
Hao Zhang
Long Qi
Huibin Zhang
Hong Liao
Chaoran Wu
Yu Li
Xinran He
Hao Sun
Shiwen Zhang
Fengsheng Hou
Mengqiu Hu
Aili Lan
Hao Zhang
Long Qi
Huibin Zhang
Hong Liao
collection Wiley Open Access
contents Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke Chaoran Wu Yu Li Xinran He Hao Sun Shiwen Zhang Fengsheng Hou Mengqiu Hu Aili Lan Hao Zhang Long Qi Huibin Zhang Hong Liao Glia AbstractIschemic 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. 10.1002/glia.24521 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/glia.24521
format Artículo Open Access
id wiley_oa_10_1002_glia_24521
institution Wiley Open Access
license_str_mv http://onlinelibrary.wiley.com/termsAndConditions#vor
publishDate 2024
publisher Wiley
record_format wiley_oa
spellingShingle Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke
Chaoran Wu
Yu Li
Xinran He
Hao Sun
Shiwen Zhang
Fengsheng Hou
Mengqiu Hu
Aili Lan
Hao Zhang
Long Qi
Huibin Zhang
Hong Liao
Glia
Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke Chaoran Wu Yu Li Xinran He Hao Sun Shiwen Zhang Fengsheng Hou Mengqiu Hu Aili Lan Hao Zhang Long Qi Huibin Zhang Hong Liao Glia AbstractIschemic 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. 10.1002/glia.24521 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke
topic Glia
url https://onlinelibrary.wiley.com/doi/10.1002/glia.24521