{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:54:15Z","timestamp":1786978455532,"version":"build-2736575974"},"reference-count":74,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T00:00:00Z","timestamp":1689379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31701045"],"award-info":[{"award-number":["31701045"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860253"],"award-info":[{"award-number":["81860253"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic social isolation (SI) stress, which became more prevalent during the COVID\u201019 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti\u2010inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three\u2010week\u2010old male mice were randomly housed for 8\u2009weeks in either group housing (GH) or SI. The animals were divided into normal saline\u2010treated GH, normal saline\u2010treated SI, and betaine\u2010treated SI groups in the sixth week. The cognitive and depression\u2010like behavior was determined in the eighth week. We found that long\u2010term betaine administration improved cognitive behavior in SI mice but failed to prevent depression\u2010like behavior. Moreover, long\u2010term betaine administration inhibited hippocampal microglia over\u2010activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic\u2013pituitary\u2013adrenal axis. Collectively, our findings reveal that betaine can improve SI\u2010induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.<\/jats:p>","DOI":"10.1002\/ptr.7944","type":"journal-article","created":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T08:15:25Z","timestamp":1689408925000},"page":"4755-4770","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice"],"prefix":"10.1002","volume":"37","author":[{"given":"Meng Meng","family":"Shi","sequence":"first","affiliation":[{"name":"Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao 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