engleski

TDP-43 mislocalization following a single and repetitive traumatic brain injury in the mouse cortex

The 43 kDa transactive response (TAR) DNA binding protein (TDP-43) is expressed in multiple tissues, including the brain, and it is suggested to be involved in different pathways which control specific nuclear pre- mRNA splicing and all steps of mRNA life cycle as well the regulation of non-coding RNAs, but all its physiological roles are not known and have to be determined. Moreover, TDP-43 dysregulation has been identified in frontotemporal lobar degeneration, amyotrophic lateral sclerosis and in a number of other neurodegenerative disorders. Recent data indicate that TDP-43 could also be included in pathophysiological processes initiated by traumatic brain injury (TBI) but its role remains unclear. TBI is a major public health problem. Single brain trauma is usually caused by traffic accidents and falls while the repetitive form of the injury is frequently the consequence of the sports, recreational and military accidents and violence. Therefore, in this study the effects of a single and repetitive TBI on the TDP-43 cytoplasmic and nuclear expressions in the mouse cortex were examined. Experiments were performed on adult male C57BL/6J mice. Single moderate lateral fluid percussion injury was performed over the left parietal cortex (McIntosh et al., 1989). Repetitive mild TBI was induced during five consecutive days, twice daily, with 6 h intervals, according to the weight drop method (Kane et al., 2012). Control, sham-injured animals went through the corresponding procedures without receiving head impacts. Mice were sacrificed at different time points after the trauma or sham procedures and their brains were prepared for immunohistological analyses. Brain slices were double-stained with TDP-43 antibody together with antibodies against specific neuronal, astrocytic or microglial markers. TDP-43 nuclear expression was detected in all mentioned cell types of investigated brain structure in the injured animals and also in the mice of the control groups. In the animals with TBI, TDP-43 cytoplasmic localization was found in the cortical neurons and the microglia at different time points after the brain trauma. In conclusion, a single as well as repetitive TBI induces translocation of TDP-43 from the nucleus to the cytoplasm of the neurons and microglia in the mouse cortex. This research was supported by grants awarded to G.Ž. by the Croatian Science Foundation (IP- 2016-06-4602) and to K.P. by the University of Rijeka (uniri-biomed-18-199).

cortex ; mouse ; TDP-43 ; traumatic brain injury

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