Exploration of the mechanism of cognitive impairment induced by ketamine in mice based on metabolomics
- VernacularTitle:基于代谢组学探讨氯胺酮致小鼠认知障碍的机制
- Author:
Tingting LUO
1
;
Xiaoxiao YAO
1
;
Xinyi ZHAN
1
;
Yiru MA
1
;
Ting GAO
1
;
Ying WEI
1
Author Information
1. School of Pharmacy，North Sichuan Medical College，Sichuan Nanchong 637000，China
- Publication Type:Journal Article
- Keywords:
ketamine;
cognitive impairment;
neurotoxicity;
metabolomics;
metabolic pathways
- From:
China Pharmacy
2025;36(12):1436-1441
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the potential mechanism of ketamine-induced cognitive impairment in mice based on metabolomics. METHODS Male C57BL/6 mice were randomly divided into control group and ketamine group （25 mg/kg）， with 12 mice in each group. Each group of mice was intraperitoneally injected with normal saline or corresponding drugs， 4 times a day， for 10 consecutive days. On the last 2 days of drug administration， the cognitive behavior was evaluated by Y maze and novel object recognition test， and the histopathological changes in the prefrontal cortex （PFC） were observed. Ultra-high performance liquid chromatography-tandem mass spectrometry technology was used to analyze the changes of metabolites in PFC， screen for differential metabolites， and perform pathway enrichment analysis. RESULTS Compared with the control group， the morphology of PFC neurons in the ketamine group of mice was inconsistent. There were cavities around the nucleus， and the number of deeply stained cells increased. The mean optical density value of the Nissl staining positive area was significantly reduced， and the alternation rate and discrimination index were significantly reduced （P＜0.05 or P＜0.01）. In the PFC tissue samples of mice of the two groups， there were a total of 114 differential metabolites， including 73 up-regulated and 41 down-regulated metabolites， including glutamine， succinic acid， ketoglutarate， and choline， etc. The differential metabolites mentioned above were mainly enriched in metabolism of alanine， aspartate and glutamate， metabolism of arginine and proline， γ aminobutyric acid synapses， pyrimidine metabolism， cholinergic synapses pathways， etc. CONCLUSIONS Ketamine can induce cognitive impairment in mice. Its neurotoxicity is related to abnormal synaptic transmission and energy metabolism， and neuroimmune regulation disorders.
