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We examined TDP-43 regulation, neurodegeneration, and glial responses following repetitive mTBI in nontransgenic mice and in animals with overexpression of human mutant TDP-43 protein (TDP-43G348C). In the frontal cortices of the injured nontransgenic animals, early TDP-43 cytoplasmatic translocation and overexpression of the protein and its pathological forms were detected. In the injured animals of both genotypes, neurodegeneration and pronounced glial activity were detected in the optic tract. In TDP-43G348C mice, these changes were significantly higher at day 7 after the last mTBI compared with the values in the nontransgenic animals. Results of this study suggest that the changes in the TDP-43 regulation in the frontal cortices of the nontransgenic animals were a transient stress response to the brain injury. Repetitive mTBI did not produce additional TDP-43 dysregulation or neurodegeneration or pronounced gliosis in the frontal cortex of TDP-43G348C mice. Our research also suggests that overexpression of mutated human TDP-43 possibly predisposes the brain to more intense neurodegeneration and glial activation in the optic tract after repetitive mTBI.<\/jats:p>","DOI":"10.1093\/jnen\/nlaa130","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T23:49:03Z","timestamp":1605916143000},"page":"2-14","source":"Crossref","is-referenced-by-count":14,"title":["Repetitive Traumatic Brain Injury Is Associated With TDP-43 Alterations, Neurodegeneration, and Glial Activation in Mice"],"prefix":"10.1093","volume":"80","author":[{"given":"Jelena","family":"Raji\u010d Bumber","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, Faculty of Medicine, University of Rijeka , Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Pilipovi\u0107","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Faculty of Medicine, University of Rijeka , Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Jankovi\u0107","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Faculty of Medicine, University of Rijeka , Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Dolenec","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Faculty of Medicine, University of Rijeka , Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nika","family":"Gr\u017eeta","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Faculty of Medicine, University of Rijeka , Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasna","family":"Kri\u017e","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuroscience, Faculty of Medicine, University of Laval , Quebec, QC, 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