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This study examined whether inhibiting the mTOR pathway, neuroinflammatory signaling, or both reduces behavioral comorbidities in adulthood. Female C57BL\/6J mice received kainic acid on postnatal day 10 to induce status epilepticus. Three hours later, the mice were treated with saline, minocycline, rapamycin, or both. Three months later, behavioral assessments were conducted that measured activity, anxiety, social behavior, repetitive behavior, and learning. Early-life seizures resulted in social behavior deficits in the social chamber test, altered anxiety in the elevated plus maze, and an increase in repetitive behavior in the nose poke assay. Rapamycin and minocycline\/rapamycin groups showed reduced distance traveled in the saline groups. We did not find any changes in cytokines IL6, IL-1\u03b2, and TNF\u03b1 in the hippocampus or cortex using RT-qPCR. Through Western blotting, we found that rapamycin reduced the phosphorylated S6 levels. Minocycline decreased phosphorylated S6 in controls, but restored phosphorylated S6 levels in the seizure group. Early-life seizures had long-term impacts on behavioral comorbidities. Rapamycin and minocycline, alone or combined, did not restore the behavioral or molecular changes after early-life seizures. These findings clarify the behavioral outcomes after early-life seizures and therapeutic modulation.<\/jats:p>","DOI":"10.3390\/neurosci7030055","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:01:30Z","timestamp":1777975290000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rapamycin and Minocycline Treatment Does Not Rescue Behavioral and Molecular Changes Induced by Early-Life Seizures in Female Mice"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1327-5738","authenticated-orcid":false,"given":"Sydney F.","family":"Pell","sequence":"first","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-4041","authenticated-orcid":false,"given":"Katherine J.","family":"Blandin","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor R.","family":"Bradish","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chloe V.","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3784-2036","authenticated-orcid":false,"given":"Danielle","family":"Santana-Coelho","sequence":"additional","affiliation":[{"name":"Long School of Medicine, The University of Texas at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madison","family":"Wallis","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3124-9617","authenticated-orcid":false,"given":"Colton W.","family":"Kelley","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josh J.","family":"Thayil","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8886-5863","authenticated-orcid":false,"given":"Ashley","family":"Smelley","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gautham","family":"Cheliah","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Narvaiz","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendall N.","family":"Lally","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1319-3505","authenticated-orcid":false,"given":"Leighton","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6874-8718","authenticated-orcid":false,"given":"Joaquin N.","family":"Lugo","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Baylor University, Waco, TX 76798, USA"},{"name":"Department of Biology, Baylor University, Waco, TX 76798, USA"},{"name":"Baylor Center for Developmental Disabilities, Baylor University, Waco, TX 76798, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1007\/s10803-014-2126-6","article-title":"Epilepsy Among Children and Adolescents with Autism Spectrum Disorders: A Population-Based Study","volume":"44","author":"Jokiranta","year":"2014","journal-title":"J. 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