Repetitive Traumatic Brain Injury Is Associated With TDP-43 Alterations, Neurodegeneration, and Glial Activation in Mice (CROSBI ID 286382)
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Podaci o odgovornosti
Rajič Bumber, Jelena ; Pilipović, Kristina ; Janković, Tamara ; Dolenec, Petra ; Gržeta, Nika ; Križ, Jasna ; Župan, Gordana
engleski
Repetitive Traumatic Brain Injury Is Associated With TDP-43 Alterations, Neurodegeneration, and Glial Activation in Mice
Increasing evidence points to a relationship between repetitive mild traumatic brain injury (mTBI), the Tar DNA binding protein 43 (TDP-43) pathology and some neurodegenerative diseases, but the underlying pathophysiological mechanisms are still unknown. 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.
Brain concussion ; Mouse ; Nerve degeneration ; Neuroglia ; TDP-43 protein
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Podaci o izdanju
80 (1)
2021.
2-14
objavljeno
0022-3069
0022-3069
10.1093/jnen/nlaa130
Povezanost rada
Temeljne medicinske znanosti