The Department of Clinical Laboratory, the 4th Affiliated Hospital of Harbin Medical University, 32 Yi-Yuan Street, NanGang District, Harbin 150001, China. Electronic address: Jiarenliu@hrbmu.edu.cn.
2 papers in the library · 6 citations · publishing 2024-2025
Ketamine, an anesthetic, reduces levels of the DISC1 protein in the brains of newborn rats, which is linked to increased activity of GSK-3β, an enzyme involved in cell signaling. This reduction corresponds to decreased axonal growth and increased cell death. Lithium, a GSK-3β antagonist, reverses these effects, suggesting a connection between DISC1 and ketamine-induced neurodegeneration.
Repeated ketamine exposure in neonatal rats reduces levels of DISC1 and several signaling proteins (pGSK-3β, β-catenin, pERK, pCREB, PSD95), leading to neuroapoptosis, inhibited neurite growth, and cognitive deficits in adolescence. Lithium treatment upregulates DISC1 and activates the GSK-3β/β-catenin and ERK/CREB pathways, thereby ameliorating these harmful effects. The findings suggest lithium may protect against ketamine-induced long-term neurotoxicity during brain development.