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GanDouLing promotes proliferation and differentiation of neural stem cells in the mouse model of Wilson’s disease

Wilson’s disease (WD) is an autosomal recessive disease caused by mutation of the ATPase copper transporting β (ATP7B) gene, resulting in abnormal copper metabolism. We aimed to investigate the protective effect of GanDouLing (GDL) on neural stem cell (NSC) function in a mouse model of WD. NSCs were...

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Autores principales: Dong, Ting, Wu, Ming-cai, Tang, Lu-lu, Jiang, Hai-lin, Zhou, Ping, Kuang, Chun-jun, Tian, Li-wei, Yang, Wen-ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786325/
https://www.ncbi.nlm.nih.gov/pubmed/33300046
http://dx.doi.org/10.1042/BSR20202717
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author Dong, Ting
Wu, Ming-cai
Tang, Lu-lu
Jiang, Hai-lin
Zhou, Ping
Kuang, Chun-jun
Tian, Li-wei
Yang, Wen-ming
author_facet Dong, Ting
Wu, Ming-cai
Tang, Lu-lu
Jiang, Hai-lin
Zhou, Ping
Kuang, Chun-jun
Tian, Li-wei
Yang, Wen-ming
author_sort Dong, Ting
collection PubMed
description Wilson’s disease (WD) is an autosomal recessive disease caused by mutation of the ATPase copper transporting β (ATP7B) gene, resulting in abnormal copper metabolism. We aimed to investigate the protective effect of GanDouLing (GDL) on neural stem cell (NSC) function in a mouse model of WD. NSCs were treated with different concentrations of GDL alone or in combination with penicillamine, following which we evaluated cellular growth, apoptosis, and differentiation. Nuclear factor E2-related factor 2 (Nrf2) pathway and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation were analyzed via Western blotting. Treatment with GDL alone or in combination with penicillamine significantly increased proliferation and inhibited apoptosis of NSCs in a dose-dependent manner. In addition, GDL treatment remarkably promoted differentiation of NSCs. Consistently, levels of class III β-tubulin (Tuj1) and microtubule-associated protein 2 (MAP2) were significantly elevated, whereas glial fibrillary acidic protein (GFAP) levels were obviously suppressed in the presence of GDL or penicillamine. In vivo assays confirmed that GDL increased the ratio of Ki67(+), Tuj1(+), and MAP2(+) cells and suppressed apoptosis in the hippocampal region in WD mice. Behavioral assays revealed that both GDL and penicillamine improved memory ability in WD models. Mechanistically, GDL treatment led to activation of Nrf2 signaling and suppression of the NLRP3 inflammasome in WD mice. Notably, inhibition of Nrf2 signaling reversed the protective effects of GDL on hippocampal NSCs. Collectively, these findings demonstrate that GDL exerts a protective effect on NSCs and promotes neurogenesis by targeting Nrf2 signaling and the NLRP3 inflammasome in WD.
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spelling pubmed-77863252021-01-13 GanDouLing promotes proliferation and differentiation of neural stem cells in the mouse model of Wilson’s disease Dong, Ting Wu, Ming-cai Tang, Lu-lu Jiang, Hai-lin Zhou, Ping Kuang, Chun-jun Tian, Li-wei Yang, Wen-ming Biosci Rep Neuroscience Wilson’s disease (WD) is an autosomal recessive disease caused by mutation of the ATPase copper transporting β (ATP7B) gene, resulting in abnormal copper metabolism. We aimed to investigate the protective effect of GanDouLing (GDL) on neural stem cell (NSC) function in a mouse model of WD. NSCs were treated with different concentrations of GDL alone or in combination with penicillamine, following which we evaluated cellular growth, apoptosis, and differentiation. Nuclear factor E2-related factor 2 (Nrf2) pathway and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation were analyzed via Western blotting. Treatment with GDL alone or in combination with penicillamine significantly increased proliferation and inhibited apoptosis of NSCs in a dose-dependent manner. In addition, GDL treatment remarkably promoted differentiation of NSCs. Consistently, levels of class III β-tubulin (Tuj1) and microtubule-associated protein 2 (MAP2) were significantly elevated, whereas glial fibrillary acidic protein (GFAP) levels were obviously suppressed in the presence of GDL or penicillamine. In vivo assays confirmed that GDL increased the ratio of Ki67(+), Tuj1(+), and MAP2(+) cells and suppressed apoptosis in the hippocampal region in WD mice. Behavioral assays revealed that both GDL and penicillamine improved memory ability in WD models. Mechanistically, GDL treatment led to activation of Nrf2 signaling and suppression of the NLRP3 inflammasome in WD mice. Notably, inhibition of Nrf2 signaling reversed the protective effects of GDL on hippocampal NSCs. Collectively, these findings demonstrate that GDL exerts a protective effect on NSCs and promotes neurogenesis by targeting Nrf2 signaling and the NLRP3 inflammasome in WD. Portland Press Ltd. 2021-01-05 /pmc/articles/PMC7786325/ /pubmed/33300046 http://dx.doi.org/10.1042/BSR20202717 Text en © 2021 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Neuroscience
Dong, Ting
Wu, Ming-cai
Tang, Lu-lu
Jiang, Hai-lin
Zhou, Ping
Kuang, Chun-jun
Tian, Li-wei
Yang, Wen-ming
GanDouLing promotes proliferation and differentiation of neural stem cells in the mouse model of Wilson’s disease
title GanDouLing promotes proliferation and differentiation of neural stem cells in the mouse model of Wilson’s disease
title_full GanDouLing promotes proliferation and differentiation of neural stem cells in the mouse model of Wilson’s disease
title_fullStr GanDouLing promotes proliferation and differentiation of neural stem cells in the mouse model of Wilson’s disease
title_full_unstemmed GanDouLing promotes proliferation and differentiation of neural stem cells in the mouse model of Wilson’s disease
title_short GanDouLing promotes proliferation and differentiation of neural stem cells in the mouse model of Wilson’s disease
title_sort gandouling promotes proliferation and differentiation of neural stem cells in the mouse model of wilson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786325/
https://www.ncbi.nlm.nih.gov/pubmed/33300046
http://dx.doi.org/10.1042/BSR20202717
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