RNAseq Analysis of the Cerebellum Reveals Significant Gene Dysregulation That May Explain Chronic Disease Progression in Mild Traumatic Brain Injury.

Abstract

Mild traumatic brain injury (mTBI) is a major public health concern worldwide and contributes to chronic, persistent neurodegenerative diseases; however, the mechanisms are not fully understood. Most studies have examined cerebral cortex, hippocampus, and thalamus brain tissue, but the impact on the cerebellum following repetitive mTBI (rmTBI) leading to secondary injury cascades and long-term pathophysiology is largely unexplored. This study investigated changes in gene expression in cerebellum tissue from an established murine model of rmTBI. The cerebellum tissue from 15 male C57BL/6J mice was analyzed using RNA sequencing technology for animals sacrificed 48 h (acute) and 90 days (chronic) following a repetitive mild impact schedule. Differentially expressed gene (DEG) analysis showed no dysregulated genes above log2 fold change at 48 h, but 360 DEGs at 90 days. At 90 days, multiple Gene Ontologies were different to controls, including disruption to mitochondria, proteosomes, ribosomes, and a reduction in vital cellular energy processes. Kyoto Encyclopedia of Genes and Genomes pathway analysis in the chronic injury group revealed that dysregulated genes were characteristic of multiple neurological diseases, including Parkinson's and Huntington's disease genetic signatures. This data demonstrates that the cerebellum and other brain regions disparate from the site of impact are more than just a bystander in chronic neurodegenerative pathologies and provides a vital link to the development of neurological disorders like Parkinson's disease from rmTBI trauma.