Early onset senescence and cognitive impairment in a murine model of repeated mTBI

Acta Neuropathologica Communications

Schwab N, Ju Y, Hazrati LN. Early onset senescence and cognitive impairment in a murine model of repeated mTBI. Acta Neuropathol Commun. 2021 May 8;9(1):82. doi: 10.1186/s40478-021-01190-x. PMID: 33964983; PMCID: PMC8106230.

Mild traumatic brain injury is a risk factor for neurodegenerative diseases. There is an increase in oxidative stress that can lead to DNA damage that overwhelms the cells damage response mechanisms. Brain cells may start to become senescent with repeated activation of the DDR pathway. This paper uses a mouse model with repeated mild traumatic brain injury (rmTBI) to examine the role of senescence in mTBI related neurodegeneration.

The injured mice showed a poorer righting reflex than the control mice as well as spatial and memory impairment. The examination of their brains revealed that they had gliosis, mircogliosis and axonal damage. rnaSeq showed that 24 hours after the injuries, the DDR was activated and cell-cycle arrest induced. Seven days after the injuries, more genes were found to be significantly different between the two mice groups. There was an increase in cellular senescence-related genes as well as genes known to be risk factors and biomarkers of neurodegenerative diseases. Several of these genes are associated with AD-like pathology which shows that neurodegenerative processes may begin as soon as a week after the injury. Further, there was a decrease in DDR gene expression which would put the brain at greater risk of damage if there were repeated incidences of TBI.