{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:42:05Z","timestamp":1785426125005,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["202209PJT-486512-CIA-CDAA-111824"],"award-info":[{"award-number":["202209PJT-486512-CIA-CDAA-111824"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"award":["202209PJT-486512-CIA-CDAA-111824"],"award-info":[{"award-number":["202209PJT-486512-CIA-CDAA-111824"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Rett Syndrome (RTT) is a progressive neurodevelopmental disorder caused by MECP2 gene mutations. MeCP2 protein binding to methylated DNA is involved in normal brain development and function. T158M is a common RTT-associated mutation, where a threonine is replaced with a methionine, affecting protein function and stability. RTT has recently been identified as a neurometabolic disorder, with metformin emerging as a potential candidate drug. Metformin is a safe and accessible drug, commonly used for Type 2 diabetes. Our team previously studied the regulatory role of metformin on the expression of RTT-related genes\/proteins using in vitro and in vivo approaches. However, the phenotypical and behavioral impact of metformin in transgenic mice carrying the common T158M mutation was not explored. Methods: Wild type (WT) and mutant Mecp2T158M (Mecp2tm4.1Bird) male mice were subjected to daily intraperitoneal injection of metformin for 20 days. The control mice received a daily intraperitoneal injection of the solvent. The main RTT-like phenotypical criteria were assessed daily. Behavioral tests included the open field test and elevated plus maze. Results: Behavioral tests indicated no significant effect of metformin on the anxiety levels, locomotion, and exploratory behaviors in the hemizygous male Mecp2T158M mice, despite our observation of increased anxiety levels in the WT counterparts. In hemizygous male Mecp2T158M mice, metformin treatment showed beneficial effects on RTT-like phenotypes, including breathing irregularities, gait abnormalities, hindlimb clasping, and overall total score. The positive effect of metformin was also observed on the body weight in the hemizygous male Mecp2T158M mice. Conclusions: Our findings provide evidence for potential therapeutic effects of metformin for MeCP2-associated neurological disorders.<\/jats:p>","DOI":"10.3390\/ph19040621","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T10:30:23Z","timestamp":1776249023000},"page":"621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin Treatment Shows Beneficial Effects on RTT-Associated Phenotypical Deficits in Mecp2 T158M Male Mice"],"prefix":"10.3390","volume":"19","author":[{"given":"Khatereh Saei","family":"Arezoumand","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghanan Bin","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8641-7969","authenticated-orcid":false,"given":"Ashraf","family":"Kadar Shahib","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica S.","family":"Jarmasz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris-Tiann","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas Rezaeian","family":"Mehrabadi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl O.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-6116","authenticated-orcid":false,"given":"Mojgan","family":"Rastegar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1002\/ana.22124","article-title":"Rett syndrome: Revised diagnostic criteria and nomenclature","volume":"68","author":"Neul","year":"2010","journal-title":"Ann. 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