engleski

Repetitive mild traumatic brain injury increases cytosolic expression, cleavage and phosphorylation of TDP-43 in the mouse frontal cortex

Repetitive mild traumatic brain injury (rmTBI) is an entity associated with multiple concussions in athletes, and it is also of particular concern among military personnel. Transactivation response DNA-binding protein 43 (TDP-43) is a ubiquitous, highly conserved protein which is under physiological conditions predominantly positioned in the cell nuclei. In pathological conditions, TDP-43 translocates to the cytoplasm where it can become hyperphosphorylated, polyubiquitinated and cleaved and consequently forms cytoplasmic inclusions characteristically found in several neurodegenerative diseases such as amyotrophic lateral sclerosis, frontotemporal dementia and Alzheimer’s disease. Purpose of this preliminary study was to determine if repeated concussions have an effect on the expression of TDP-43 including its subcellular position, cleavage and phosphorylation in mice frontal cortex during the first week after the last brain trauma. Adult male animals were subjected to the rmTBI protocol for five consecutive days. They received head impacts twice daily, with 6 h intervals, according to the weight drop method (Kane et al., 2012). Control, sham-injured animals were only lightly anesthetized and went through the same procedure without receiving head impacts. Animals were sacrificed 1, 3 or 7 days after the last trauma or sham procedure and their frontal cortices were collected for the protein expression analyses. In the cortices of the injured mice, increased cytosolic TDP-43 expression accompanied with the higher cytosolic content of 35 kDa cleaved form of this protein were detected on the first day after the last brain trauma. Furthermore, in traumatized mice, increased TDP-43 phosphorylation was also found. Preliminary results of this study showed that rmTBI causes TDP-43 cytosol overexpression, its cleavage and phosphorylation in the mouse frontal cortex within the first week after the last head impact. These results confirm the suggestion that above mentioned posttraumatic TDP-43 transformation processes could be involved in the pathogenesis of different brain disorders linked with repeated concussions. This research was supported by the Croatian Science Foundation grant IP-2016-06-4602 to G.Ž.

mouse ; repetitive traumatic brain injury ; transactivation response DNA-binding protein 43

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