Lipidomics Reveals Dysregulated Glycerophospholipid Metabolism in the Corpus Striatum of Mice Treated with Cefepime.

ACS chemical neuroscience 2021 Dec 01

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Cefepime exhibits a broad spectrum of antimicrobial activity and thus is a widely used treatment for severe bacterial infections. Adverse effects on the central nervous system (CNS) have been reported in patients treated with cefepime. Current explanation for the adverse neurobehavioral effect of cefepime is mainly attributed to its ability to cross the blood-brain barrier and competitively bind to the GABAergic receptor; however, the underlying mechanism is largely unknown. In this study, mice were intraperitoneally administered 80 mg/kg cefepime for different periods, followed by neurobehavioral tests and a brain lipidomic analysis. LC/MS-MS-based metabolomics was used to investigate the effect of cefepime on the brain lipidomic profile and metabolic pathways. Repeated cefepime treatment time-dependently caused anxiety-like behaviors, which were accompanied by reduced locomotor activity in the open field test. Cefepime profoundly altered the lipid profile, acyl chain length, and unsaturation of fatty acids in the corpus striatum, and glycerophospholipids accounted for a large proportion of those significantly modified lipids. In addition, cefepime treatment caused obvious alteration in the lipid-enriched membrane structure, neurites, mitochondria, and synaptic vesicles of primary cultured striatal neurons; moreover, the spontaneous electrical activity of striatal neurons was significantly reduced. Collectively, cefepime reprograms glycerophospholipid metabolism in the corpus striatum, which may interfere with neuronal structure and activity, eventually leading to aberrant neurobehaviors in mice.

Citation

Xiaocong Liu, Qingfan Wei, Xiaowei Yang, Xiaojie Wang, Jiamei Zhang, Rui Xu, Haoluo Zhang, Shaomin Wang, Xuemei Wan, Linhong Jiang, Yuman He, Shu Li, Rong Chen, Yonghai Wang, Yaxing Chen, Feng Qin, Yuanyuan Chen, Yanping Dai, Hongchun Li, Ying Zhao, Huaqin Zhang, Qian Bu, Hongbo Wang, Jingwei Tian, Yinglan Zhao, Xiaobo Cen. Lipidomics Reveals Dysregulated Glycerophospholipid Metabolism in the Corpus Striatum of Mice Treated with Cefepime. ACS chemical neuroscience. 2021 Dec 01;12(23):4449-4464