@article{ref1,
title="BRCA1 heterozygosity promotes DNA damage-induced senescence in a sex-specific manner following repeated mild traumatic brain injury",
journal="Frontiers in neuroscience",
year="2023",
author="Leung, Emily and Taskina, Daria and Schwab, Nicole and Hazrati, Lili-Naz",
volume="17",
number="",
pages="e1225226-e1225226",
abstract="Emerging evidence suggests cellular senescence, as a consequence of excess DNA damage and deficient repair, to be a driver of brain dysfunction following repeated mild traumatic brain injury (rmTBI). This study aimed to further investigate the role of deficient DNA repair, specifically BRCA1-related repair, on DNA damage-induced senescence. BRCA1, a repair protein involved in maintaining genomic integrity with multiple roles in the central nervous system, was previously reported to be significantly downregulated in post-mortem brains with a history of rmTBI. Here we examined the effects of impaired BRCA1-related repair on DNA damage-induced senescence and outcomes 1-week post-rmTBI using mice with a heterozygous knockout for BRCA1 in a sex-segregated manner. Altered BRCA1 repair with rmTBI resulted in altered anxiety-related behaviours in males and females using elevated zero maze and contextual fear conditioning. Evaluating molecular markers associated with DNA damage signalling and senescence-related pathways revealed sex-specific differences attributed to BRCA1, where females exhibited elevated DNA damage, impaired DNA damage signalling, and dampened senescence onset compared to males. Overall, the results from this study highlight sex-specific consequences of aberrant DNA repair on outcomes post-injury, and further support a need to develop sex-specific treatments following rmTBI.<p /> <p>Language: en</p>",
language="en",
issn="1662-4548",
doi="10.3389/fnins.2023.1225226",
url="http://dx.doi.org/10.3389/fnins.2023.1225226"
}