4.4 Article

Chronic lead exposure disrupts neurometabolic activity in mouse brain: An ex vivo 1H-[13C]-NMR study

期刊

NEUROTOXICOLOGY
卷 94, 期 -, 页码 117-125

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ELSEVIER
DOI: 10.1016/j.neuro.2022.11.005

关键词

GABA; Glutamate; Neurometabolism; TCA cycle; Neurotransmitter cycle

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Chronic lead exposure in mice leads to impaired forelimb strength and perturbed neurometabolism in brain regions involved in cognition and movement.
Lead poisoning has been identified as a problem in adults as well as in children. Chronic exposure to lead has been implicated in neurological disorders such as amyotrophic lateral sclerosis, Parkinson's disease, and Alz-heimer's disease. In the present study, we evaluated the impact of chronic lead exposure on cerebral gluta-matergic and GABAergic metabolic activity in mice. C57BL6 mice were provided lead acetate in drinking water for two months. The regional cerebral metabolic activity was measured using 1H-[13C]-NMR spectroscopy in conjunction with infusion of [1,6-13C2]glucose. The blood Pb2+ increased significantly in lead acetate treated mice. Concomitantly, there was a significant reduction in the forelimb strength. The level of myo-inositol was elevated in the cerebral cortex of mice chronically exposed to lead. The glutamatergic neurometabolic activity was found to be reduced following chronic lead exposure in the cerebral cortex, hippocampus, and striatum. In contrast, the GABAergic fluxes were impaired in the hippocampus and thalamus only. The metabolic fluxes in the cerebellum were unperturbed to Pb2+ toxicity. In conclusion, we report that chronic lead exposure in mice leads to an impairment in forelimb strength, and a perturbation in neurometabolism in brain regions involving cognition and movement.

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