engleski

EFFECTS OF A SINGLE MODERATE TRAUMATIC BRAIN INJURY IN MOUSE ON THE TAR DNA-BINDING PROTEIN 43 AND ITS CONNECTION WITH NEUROINFLAMMATION AND SYNAPTIC PLASTICITY

Traumatic brain injury (TBI) is a lifelong condition that leads to progressive brain damage and cognitive disturbances. TBI has been recognized as a risk factor for the development of numerous neurodegenerative diseases, such as Alzheimer and Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Proteinopathy of TAR DNA binding protein 43 (TDP-43) is considered the most important pathological characteristic of ALS and FTLD, that is characterized by permanent translocation of TDP-43 in the cytoplasm where this protein undergoes hyperphosphorylation, ubiquitination and fragmentation with subsequent inclusion formation. Toxic effects of TDP-43 inclusions have been demonstrated in the neurons and microglia, but deficiency of nuclear TDP-43 has numerous cell consequences too. Although cellular processes that induce TDP-43 proteinopathy are still unclear, it has been proven that inflammation can induce these changes. Interconnection of TDP-43 with some synaptic proteins has also been found. TDP-43 inclusions have been detected in the brain tissue after repetitive trauma in numerous clinical and preclinical investigations and it is mostly considered that this type of proteinopathy is only a consequence of repetitive, but with a single TBI, results have thus far been inconclusive. The aim of this study was to investigate the changes in the TDP- 43 localization, fragmentation, and phosphorylation in different brain regions after a single moderate TBI in mice. Additionally, we examined the association of TDP-43 expression with some markers of synaptogenesis and inflammation. This work was supported by the University of Rijeka, Croatia, project-uniri- biomed-18-199 to K.P. and Croatian Science Foundation project-IP-2016-06-4602 to GŽ.

TDP-43, Cortex, Hippocampus, Traumatic brain injury

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