engleski

Single moderate traumatic brain injury in mice causes misslocalization and phosphorylation of transactive response binding protein 43 in the parietal cortex

Introduction: Transactive response DNA-binding protein 43 (TDP-43) is a ubiquitous protein that controls gene expression and it is mainly located in the nuclei. In some neurodegenerative diseases, it was found that TDP-43 translocates to the cytoplasm where it forms phosphorylated, ubiquitinated and proteolytically cleaved deposits which may cause neurotoxicity. Aim of this preliminary study was to investigate the changes in TDP-43 subcellular position, degradation, and phosphorylation in the mouse parietal cortex after a single traumatic brain injury (TBI). Materials and Methods: Moderate severity TBI was induced over the left parietal cortex in adult male mice using the lateral fluid percussion injury apparatus. Animals were sacrificed 1, 3 or 14 days after the trauma and their brains were prepared for Western blot or immunohistological analyses. Animals of the control group were sacrificed 1 day after the sham procedure. Results: In the injured mice, an increase in the cortical expression of the cytoplasmic TDP- 43 was detected on the first and the third day, and decrease in the nuclear TDP-43 expression on the third day after TBI. The phosphorylated form of 35 kDa cleavage product of TDP-43 was also observed in the injured animals’ cortices. Co-labeling of TDP- 43 with neuronal and microglial markers revealed cytoplasmic mislocalization of this protein in these cell types. Conclusion: Our preliminary results showed that a single moderate TBI causes changes in the TDP-43 expression in the mouse parietal cortex.

Traumatic brain injury, TDP-43, mice, cortex

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