Ciliopathy interacts with neonatal anesthesia to cause non-apoptotic caspase-mediated motor deficits.
bioRxiv : the preprint server for biology November 27, 2024 Nemanja Sarić, Zeynep Atak, Courtni Foster Sade et al. preprint
Ketamine anesthesia given briefly to newborn mice with a genetic cilia defect causes lasting motor skill problems. These mice already have fewer spines on neurons in a key brain layer, and ketamine disrupts the spine changes normally seen during motor learning. The damage involves a non-lethal activation of caspase enzymes. Blocking caspase in newborns restored both spine density and motor performance, showing that this enzyme signaling is necessary for proper brain development. The findings suggest that children with cilia-related genetic conditions, such as those with congenital heart disease, may be especially vulnerable to anesthesia-induced developmental harm, and that targeting caspase could offer a protective strategy.