Ketamine administration causes cognitive impairment by destroying the circulation function of the glymphatic system.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 1, 2024 Xue Wu, Gehua Wen, Lei Yan et al. 11 citations
Ketamine, a drug originally used as an anesthetic and now commonly abused in China, can cause cognitive impairment by disrupting the brain's glymphatic system, which normally clears metabolic waste. In a mouse model of short-term ketamine administration, the drug increased expression of the 5-HT2c receptor in hippocampal astrocytes, leading to accumulation of the transcription factor ΔFosb. ΔFosb then bound to a specific DNA sequence in the regulatory region of the Aqp4 gene, suppressing Aqp4 expression and impairing glymphatic circulation, which resulted in cognitive deficits. This mechanism does not involve the Pten/Akt pathway and reveals a non-neuronal basis for ketamine-induced cognitive harm, informing clinical safety and withdrawal effectiveness.