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Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia

AIMS: Cerebral ischemia can lead to anxiety and cognitive impairment due to the loss of hippocampal neurons. Facilitation of endogenous neurogenesis in the hippocampus is a potential therapeutic strategy for alleviating ischemia‐induced anxiety and cognitive impairment. Progranulin (PGRN), a secreto...

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Autores principales: Sun, Siqi, Zhou, Jinlong, Li, Zhongqi, Wu, Yuzi, Wang, Hao, Zheng, Qi, Adu‐Nti, Frank, Fan, Juan, Tian, Yingfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981488/
https://www.ncbi.nlm.nih.gov/pubmed/35146924
http://dx.doi.org/10.1111/cns.13810
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author Sun, Siqi
Zhou, Jinlong
Li, Zhongqi
Wu, Yuzi
Wang, Hao
Zheng, Qi
Adu‐Nti, Frank
Fan, Juan
Tian, Yingfang
author_facet Sun, Siqi
Zhou, Jinlong
Li, Zhongqi
Wu, Yuzi
Wang, Hao
Zheng, Qi
Adu‐Nti, Frank
Fan, Juan
Tian, Yingfang
author_sort Sun, Siqi
collection PubMed
description AIMS: Cerebral ischemia can lead to anxiety and cognitive impairment due to the loss of hippocampal neurons. Facilitation of endogenous neurogenesis in the hippocampus is a potential therapeutic strategy for alleviating ischemia‐induced anxiety and cognitive impairment. Progranulin (PGRN), a secretory glycoprotein, has been reported to have a mitogentic effect on many cell types. However, it is not clear whether PGRN enhances hippocampal neurogenesis and promotes functional recovery. METHODS: Adult male C57BL/6 mice were subjected to permanent middle cerebral artery occlusion (pMCAO) and injected intracerebroventricularly with recombinant mouse PGRN 30 min after pMCAO. Anxiety‐like behavior was detected by the open field and the elevated plus maze tests, and spatial learning and memory abilities were evaluated by Morris water maze. Neurogenesis was examined by double labeling of BrdU and neural stem cells or neurons markers. For mechanism studies, the level of ERK1/2 and AKT phosphorylation were assessed by western blotting. RESULTS: Progranulin significantly alleviated anxiety‐like behavior and spatial learning and memory impairment induced by cerebral ischemia in mice. Consistent with the functional recovery, PGRN promoted neural stem cells (NSCs) proliferation and neuronal differentiation in the dentate gyrus (DG) after cerebral ischemia. PGRN upregulated the expression of phosphorylated ERK1/2 and Akt in the DG after cerebral ischemia. CONCLUSIONS: Progranulin alleviates ischemia‐induced anxiety‐like behavior and spatial learning and memory impairment in mice, probably via stimulation of hippocampal neurogenesis mediated by activation of MAPK/ERK and PI3K/Akt pathways. PGRN might be a promising candidate for coping with ischemic stroke‐induced mood and cognitive impairment in clinic.
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spelling pubmed-89814882022-04-11 Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia Sun, Siqi Zhou, Jinlong Li, Zhongqi Wu, Yuzi Wang, Hao Zheng, Qi Adu‐Nti, Frank Fan, Juan Tian, Yingfang CNS Neurosci Ther Original Articles AIMS: Cerebral ischemia can lead to anxiety and cognitive impairment due to the loss of hippocampal neurons. Facilitation of endogenous neurogenesis in the hippocampus is a potential therapeutic strategy for alleviating ischemia‐induced anxiety and cognitive impairment. Progranulin (PGRN), a secretory glycoprotein, has been reported to have a mitogentic effect on many cell types. However, it is not clear whether PGRN enhances hippocampal neurogenesis and promotes functional recovery. METHODS: Adult male C57BL/6 mice were subjected to permanent middle cerebral artery occlusion (pMCAO) and injected intracerebroventricularly with recombinant mouse PGRN 30 min after pMCAO. Anxiety‐like behavior was detected by the open field and the elevated plus maze tests, and spatial learning and memory abilities were evaluated by Morris water maze. Neurogenesis was examined by double labeling of BrdU and neural stem cells or neurons markers. For mechanism studies, the level of ERK1/2 and AKT phosphorylation were assessed by western blotting. RESULTS: Progranulin significantly alleviated anxiety‐like behavior and spatial learning and memory impairment induced by cerebral ischemia in mice. Consistent with the functional recovery, PGRN promoted neural stem cells (NSCs) proliferation and neuronal differentiation in the dentate gyrus (DG) after cerebral ischemia. PGRN upregulated the expression of phosphorylated ERK1/2 and Akt in the DG after cerebral ischemia. CONCLUSIONS: Progranulin alleviates ischemia‐induced anxiety‐like behavior and spatial learning and memory impairment in mice, probably via stimulation of hippocampal neurogenesis mediated by activation of MAPK/ERK and PI3K/Akt pathways. PGRN might be a promising candidate for coping with ischemic stroke‐induced mood and cognitive impairment in clinic. John Wiley and Sons Inc. 2022-02-10 /pmc/articles/PMC8981488/ /pubmed/35146924 http://dx.doi.org/10.1111/cns.13810 Text en © 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Sun, Siqi
Zhou, Jinlong
Li, Zhongqi
Wu, Yuzi
Wang, Hao
Zheng, Qi
Adu‐Nti, Frank
Fan, Juan
Tian, Yingfang
Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
title Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
title_full Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
title_fullStr Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
title_full_unstemmed Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
title_short Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
title_sort progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981488/
https://www.ncbi.nlm.nih.gov/pubmed/35146924
http://dx.doi.org/10.1111/cns.13810
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