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Glycogen synthase kinase\u20103\u03b2 (GSK\u20103\u03b2) signaling is essential for the coordination of progenitor cell proliferation and differentiation during brain development. The mechanisms by which GSK\u20103\u03b2 is involved in dietary restriction\u2010induced neurogenesis and cognitive improvement remain unclear. Six\u2010month\u2010old male 3xTg\u2010AD and wild\u2010type mice were fed on alternate days (intermittent fasting, IF) or ad libitum (AL) for 3\u00a0months. GSK\u20103\u03b2 activity was regulated by bilaterally infusing lentiviral vectors carrying siRNA targeting GSK\u20103\u03b2 into the dentate gyrus region of the hippocampus. Intermittent fasting promoted neuronal differentiation and maturation in the dentate gyrus and ameliorated recognized dysfunction in 3xTg\u2010AD mice. These effects were reversed by siRNA targeting GSK\u20103\u03b2. After intermittent fasting, the insulin and protein kinase A signaling pathways were inhibited, while the adenosine monophosphate\u2010activated protein kinase and brain\u2010derived neurotrophic factor pathways were activated. These findings suggest that intermittent fasting can promote neuronal differentiation and maturation in the hippocampus by activating GSK\u20103\u03b2, thus improving learning and memory.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15105-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15105","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:21:32Z","timestamp":1592958092000},"page":"697-713","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK\u20103\u03b2 in 3xTg\u2010AD mice"],"prefix":"10.1111","volume":"155","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1597-8987","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of State Administration of Traditional Chinese Medicine of China Department of Pathophysiology School of Medicine Institute of Brain Research Jinan University Guangzhou P. 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