Xue Wu

2 papers in the library · 11 citations · publishing 2022-2024

Papers

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.

DOI: 10.1016/j.biopha.2024.116739 Full text Ketamine 5-ht2c Aqp4 Cognitive impairment +7

Ketamine enhances dopamine D1 receptor expression by modulating microRNAs in a ketamine-induced schizophrenia-like mouse model.

Neurotoxicology and Teratology February 21, 2022 Xiaojiaoyang Li, Juanhan Yu, Xue Wu et al.

High-dose ketamine given to mice for seven consecutive days produced schizophrenia-like symptoms, including increased activity and impaired spatial learning and memory. Ketamine reduced levels of three microRNAs (miR-15a-3p, miR-15b-3p, miR-16-1-3p) in the prefrontal cortex and one (miR-16-1-3p) in the hippocampus, while increasing expression of the dopamine D1 receptor (DRD1) in those brain regions. In mouse hippocampal neurons, ketamine raised DRD1 levels in a dose-dependent way, and adding mimics of miR-15b-3p and miR-16-1-3p partially reversed this increase. A specific sequence in the DRD1 gene's regulatory region was identified as the target of these microRNAs.

DOI: 10.1016/j.ntt.2022.107079 Medicine