Protective effect of low-dose radiation on doxorubicin-induced brain injury in mice

Gao, Yan; Dong, Jingyao; Chen, Mengmeng; Wang, Taiwei; Yang, Zhaoyun; He, Kang; Li, Yuewei; Wang, Kai; Jiang, Jian; Zhang, Shuang

doi:10.1016/j.abb.2022.109390

Cited by 2 publications

(1 citation statement)

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“…Low-dose radiation (LDR) is another method that has been shown to promote DNA repair, reduce DNA damage, and attenuate oxidative stress ( Xu et al, 2022 ). In the context of injury, LDR treatment prior to doxorubicin-induced brain injury in BALB/C mice was shown to combat oxidative damage and downregulate expression of proapoptotic proteins ( Gao et al, 2022 ). Cumulatively these studies not only emphasize the importance of sufficient DNA repair to mitigate consequences of stress and insults, but also the need to explore alternative therapeutic avenues to effectively treat symptoms following rmTBI in a sex-specific manner.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 heterozygosity promotes DNA damage-induced senescence in a sex-specific manner following repeated mild traumatic brain injury

et al. 2023

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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.

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Section: Discussionmentioning

confidence: 99%