Esketamine alleviates cognitive impairment signs induced by modified electroconvulsive therapy in a depression rat model via the KLF4/p38 MAPK pathway.
Journal of affective disorders May 1, 2025 Xiaohui Zhou, Li Zhang, Weiwei Gao et al. 4 citations
In a rat model of depression, modified electroconvulsive therapy (MECT) effectively reduced depressive symptoms but worsened cognitive impairments, increased hippocampal neuronal death, and triggered neuroinflammation. Adding esketamine, an FDA-approved antidepressant, reversed those cognitive deficits, reduced cell death and inflammation, and improved synaptic plasticity. Esketamine worked by increasing levels of the protein KLF4, which in turn blocked the p38 MAPK signaling pathway. When KLF4 was experimentally reduced, esketamine's protective effects disappeared, confirming its essential role. The findings suggest that combining esketamine with electroconvulsive therapy could protect against memory and thinking problems in patients.