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Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
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Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
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Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
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Journal Article
Progranulin promotes hippocampal neurogenesis and alleviates anxiety‐like behavior and cognitive impairment in adult mice subjected to cerebral ischemia
2022
Overview
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. Progranulin alleviates anxiety‐like behavior and spatial learning and memory impairment induced by cerebral ischemia, which is due to stimulating hippocampal neurogenesis through activation of MAPK/ERK and PI3K/Akt signaling pathways.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
1-Phosphatidylinositol 3-kinase
/ Animals
/ Anxiety
/ Behavior
/ Brain Ischemia - complications
/ Brain Ischemia - drug therapy
/ Cognitive Dysfunction - drug therapy
/ Cognitive Dysfunction - etiology
/ Cognitive Dysfunction - metabolism
/ Design
/ Infarction, Middle Cerebral Artery - metabolism
/ Ischemia
/ Male
/ Memory
/ Mice
/ Original
/ Phosphatidylinositol 3-Kinases - metabolism
/ Progranulins - therapeutic use
/ Spatial discrimination learning
/ Stroke
/ Surgery
