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In depression, there exists a reduction in the availability of dendritic spines in the frontal cortex (FC) and hippocampus (Hp). In addition, histone modification and DNA methylation are also dysregulated epigenetic mechanisms in depression. Repetitive transcranial magnetic stimulation (rTMS) is a technique that is used to treat depression. However, the epigenetic mechanisms of its therapeutic effect are still not known. Therefore, in this study, we evaluated the antidepressant effect of 5 Hz rTMS and examined its effect on dendritic remodeling, immunoreactivity of synapse proteins, histone modification, and DNA methylation in the FC and Hp in a model of chronic mild stress. Our data indicated that stress generated depressive-like behaviors and that rTMS reverses this effect, romotes the formation of dendritic spines, and favors the presynaptic connection in the FC and DG (dentate gyrus), in addition to increasing histone H3 trimethylation and DNA methylation. These results suggest that the antidepressant effect of rTMS is associated with dendritic remodeling, which is probably regulated by epigenetic mechanisms. These data are a first approximation of the impact of rTMS at the epigenetic level in the context of depression. Therefore, it is necessary to analyze in future studies as to which genes are regulated by these mechanisms, and how they are associated with the neuroplastic modifications promoted by rTMS.<\/jats:p>","DOI":"10.3390\/cells12162062","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:20:14Z","timestamp":1692008414000},"page":"2062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Repetitive Transcranial Magnetic Stimulation Reduces Depressive-like Behaviors, Modifies Dendritic Plasticity, and Generates Global Epigenetic Changes in the Frontal Cortex and Hippocampus in a Rodent Model of Chronic Stress"],"prefix":"10.3390","volume":"12","author":[{"given":"David","family":"Meneses-San Juan","sequence":"first","affiliation":[{"name":"National Institute of Psychiatry \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Mexico City 14370, Mexico"},{"name":"Center of Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0297-4218","authenticated-orcid":false,"given":"M\u00f3nica","family":"Lamas","sequence":"additional","affiliation":[{"name":"Center of Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-1588","authenticated-orcid":false,"given":"Gerardo Bernab\u00e9","family":"Ram\u00edrez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"National Institute of Psychiatry \u201cRam\u00f3n de la Fuente Mu\u00f1iz\u201d, Mexico City 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.pneurobio.2019.01.006","article-title":"Sex Differences in Depression: Insights from Clinical and Preclinical Studies","volume":"176","author":"Eid","year":"2019","journal-title":"Prog. 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