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

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.

Neurons and glial cells acquire a senescent signature after repeated mild traumatic brain injury in a sex-dependent manner.

Mild traumatic brain injury (mTBI) is an important public health issue, as it can lead to long-term neurological symptoms and risk of neurodegenerative disease. The pathophysiological mechanisms driving this remain unclear, and currently there are no effective therapies for mTBI. In this study on repeated mTBI (rmTBI), we have induced three mild closed-skull injuries or sham procedures, separated by 24 h, in C57BL/6 mice.

Panx1 channels promote both anti- and pro-seizure-like activities in the zebrafish via p2rx7 receptors and ATP signaling.

The molecular mechanisms of excitation/inhibition imbalances promoting seizure generation in epilepsy patients are not fully understood. Evidence suggests that Pannexin1 (Panx1), an ATP release channel, modulates the excitability of the brain. In this report, we performed electrophysiological, behavioral, and molecular phenotyping experiments on zebrafish larvae bearing genetic or pharmacological knockouts of Panx1a and Panx1b channels, each homologous to human PANX1.