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Neurodegeneration, microglyosis and astrocytosis in the optic tract during the first week following repetitive mild traumatic brain injury in wild type and TDP-43 transgenic mice

Introduction: Repetitive mild traumatic brain injury (mTBI) is associated with the development of neurodegenerative diseases such as amyotrophic lateral sclerosis and chronic traumatic encephalopathy in which TAR DNA- binding protein 43 (TDP-43) dysregulation has been identified. The purpose of this study was to investigate if repetitive mTBI induces neurodegeneration and the changes in microglia and astrocytes in the brain during the first week after the repetitive mTBI in wild type and mice overexpressing mutant TDP-43. Materials and methods: Repetitive mTBI in C57BL/6 and TDP-43G348C (Swarup et al., 2011) mice was induced by using weight drop method (Kane et al. 2012) for five days in a row, twice daily, at intervals of six hours. Sham- injured mice of the control wild type or transgenic TDP-43 mice groups were anesthetized without receiving any injury. The animals were sacrificed 1, 3 or 7 days after the final injury or sham procedure and their brains were prepared for histological analyses. Fluoro-Jade C staining was used to identify the extent of neuronal injury. Immunofluorescence labelings of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) were performed with the aim to assess the expressions of astrocytes and microglial cells. Results: Fluoro-Jade C positive fibers as well as increased GFAP and Iba1 immunoreactivity were detected in the optic tracts of the injured wild type and TDP-43 transgenic mice at days 1, 3 and 7 after the last rmTBI. Conclusion: This preliminary study suggests the presence of neurodegenerative changes as well as of astrocytosis and microgliosis in the optic tract at early time points following repetitive mTBI in wild type and TDP43 transgenic mice. This research was fully supported by the Croatian Science Foundation under the project IP-2016-06-4602 to Ž.G.

repetitive mild traumatic brain injury, TDP-43, neurodegeneration, microglia, astrocytes, mice

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