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The present study aimed to determine whether metformin exerts beneficial effects on metabolic and neurobehavioral outcomes in the streptozotocin (STZ)\u2010induced T1D model and western diet (WD)\u2010induced obesity model in male Swiss mice. T1D was induced by intraperitoneal injection of STZ (50\u2009mg\/kg, for five consecutive days). The animals were then treated daily with saline or metformin (200\u2009mg\/kg\/day, oral gavage), and a battery of tests recapitulating different neurobehavioral anomalies related to anxiogenic\/depressive\u2010like phenotype was conducted after 18\u2009days. WD\u2010induced obesity was modeled in mice by high\u2010fat and high\u2010fructose diet (HFFD) feeding for 15\u2009days. In the sequence, control and diet\u2010induced obesity mice were treated daily with saline or metformin (200\u2009mg\/kg\/day), and a battery of behavioral tests was performed after 17\u2009days. STZ injection and WD feeding induced metabolic and neurobehavioral impairments in mice. Remarkably, metformin improved the metabolic and neurobehavioral parameters in WD\u2010induced obesity mice. Moreover, metformin ameliorated STZ\u2010induced neurobehavioral deficits while it failed to improve the associated metabolic impairments. The beneficial effects of metformin in STZ\u2010induced neurobehavioral impairments were not mediated by improving peripheral insulin signaling. Our results suggest that conventional diabetes treatment could be repurposed to simultaneously improve neurobehavioral symptoms and diabetes.<\/jats:p>","DOI":"10.1111\/fcp.12825","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T05:06:13Z","timestamp":1661231173000},"page":"94-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Metformin improves neurobehavioral impairments of streptozotocin\u2010treated and western diet\u2010fed mice: Beyond glucose\u2010lowering effects"],"prefix":"10.1111","volume":"37","author":[{"given":"Eslen","family":"Delanogare","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Neuroci\u00eancias Universidade Federal de Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Bullich","sequence":"additional","affiliation":[{"name":"Centre 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