Mitochondrial dysfunction and lipid peroxidation in rat frontal cortex by chronic NMDA administration can be partially prevented by lithium treatment

Journal of Psychiatric Research
Helena Kyunghee KimAna C Andreazza

Abstract

Chronic N-methyl-d-aspartate (NMDA) administration to rats may be a model to investigate excitotoxicity mediated by glutamatergic hyperactivity, and lithium has been reported to be neuroprotective. We hypothesized that glutamatergic hyperactivity in chronic NMDA injected rats would cause mitochondrial dysfunction and lipid peroxidation in the brain, and that chronic lithium treatment would ameliorate some of these NMDA-induced alterations. Rats treated with lithium for 6 weeks were injected i.p. 25 mg/kg NMDA on a daily basis for the last 21 days of lithium treatment. Brain was removed and frontal cortex was analyzed. Chronic NMDA decreased brain levels of mitochondrial complex I and III, and increased levels of the lipid oxidation products, 8-isoprostane and 4-hydroxynonenal, compared with non-NMDA injected rats. Lithium treatment prevented the NMDA-induced increments in 8-isoprostane and 4-hydroxynonenal. Our findings suggest that increased chronic activation of NMDA receptors can induce alterations in electron transport chain complexes I and III and in lipid peroxidation in brain. The NMDA-induced changes may contribute to glutamate-mediated excitotoxicity, which plays a role in brain diseases such as bipolar disorder. Lithi...Continue Reading

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Citations

Jul 28, 2016·Cell and Tissue Research·Andreas AufschnaiterSabrina Büttner
Jan 30, 2019·PloS One·Marcelo Soares FernandesIvana Beatrice Mânica da Cruz
Nov 5, 2019·Frontiers in Cellular Neuroscience·Fiona LimanaqiFrancesco Fornai
Jul 20, 2019·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·L HolperJ J Mann
Nov 3, 2020·Frontiers in Psychiatry·Martin LundbergMartin Schalling
May 18, 2021·Neuroscience and Biobehavioral Reviews·Tim L EmmerzaalTamas Kozicz

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