{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:23:04Z","timestamp":1789708984160,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["GK201803044"],"award-info":[{"award-number":["GK201803044"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["GK202005001"],"award-info":[{"award-number":["GK202005001"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971285"],"award-info":[{"award-number":["81971285"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>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\u2010induced 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult male C57BL\/6\u00a0mice were subjected to permanent middle cerebral artery occlusion (pMCAO) and injected intracerebroventricularly with recombinant mouse PGRN 30\u00a0min after pMCAO. Anxiety\u2010like 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Progranulin significantly alleviated anxiety\u2010like 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Progranulin alleviates ischemia\u2010induced anxiety\u2010like 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\u2010induced mood and cognitive impairment in clinic.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13810","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T03:59:04Z","timestamp":1644551944000},"page":"775-787","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Progranulin promotes hippocampal neurogenesis and alleviates anxiety\u2010like behavior and cognitive impairment in adult mice subjected to cerebral ischemia"],"prefix":"10.1111","volume":"28","author":[{"given":"Siqi","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Ministry of Education for Medicinal Plant Resource and Natural Pharmaceutical Chemistry National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China College of Life Sciences Shaanxi Normal University  Xi\u2019an 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