Brain mitochondrial metabolic dysfunction and glutamate level reduction in the pilocarpine model of temporal lobe epilepsy in mice

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Olav B SmelandKarin Borges

Abstract

Although certain metabolic characteristics such as interictal glucose hypometabolism are well established for temporal lobe epilepsy (TLE), its pathogenesis still remains unclear. Here, we performed a comprehensive study of brain metabolism in a mouse model of TLE, induced by pilocarpine-status epilepticus (SE). To investigate glucose metabolism, we injected mice 3.5-4 weeks after SE with [1,2-(13)C]glucose before microwave fixation of the head. Using (1)H and (13)C nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry and high-pressure liquid chromatography, we quantified metabolites and (13)C labeling in extracts of cortex and hippocampal formation (HF). Hippocampal levels of glutamate, glutathione and alanine were decreased in pilocarpine-SE mice compared with controls. Moreover, the contents of N-acetyl aspartate, succinate and reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H were decreased in HF indicating impairment of mitochondrial function. In addition, the reduction in (13)C enrichment of hippocampal citrate and malate suggests decreased tricarboxylic acid (TCA) cycle turnover in this region. In cortex, we found reduced (13)C labeling of glutamate, glutamine and aspartate via the py...Continue Reading

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Citations

Sep 15, 2015·Journal of Neurochemistry·Catalina Carrasco-PozoKarin Borges
Dec 3, 2015·Neurochemistry International·Puneet BaggaAnant B Patel
Jan 8, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Allison C NugentWilliam H Theodore
Oct 31, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tanya S McDonaldKarin Borges
May 27, 2015·Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging·Michael Y XuNancy A Machens
Dec 30, 2014·Oxidative Medicine and Cellular Longevity·Noemí Cárdenas-RodríguezLiliana Carmona-Aparicio
Jul 16, 2013·Neuroscience Letters·Mohd Farooq ShaikhKarin Borges
May 18, 2016·European Journal of Pharmacology·Tanveer Singh, Rajesh Kumar Goel
Jun 2, 2017·Epilepsy & Behavior : E&B·Navjot KaurRajesh Kumar Goel
Jul 14, 2018·Journal of Neurochemistry·Stefano MelettiGiuseppe Biagini
Jun 2, 2020·Epilepsia·Marshal D WolffG Campbell Teskey
Dec 7, 2016·Pharmacological Reports : PR·Tanveer Singh, Rajesh Kumar Goel
Nov 23, 2016·Neurochemical Research·Jan Albrecht, Magdalena Zielińska
Nov 22, 2016·Neurochemical Research·Tesfaye W TeferaKarin Borges
Aug 6, 2017·Scientific Reports·Juan LiuShengtian Li
Mar 14, 2019·Behavioural Neurology·Ebrahim M YimerAbadi Kahsu Gebre
Mar 21, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tanya McDonaldKarin Borges
Sep 21, 2017·Frontiers in Neurology·Federica MurgiaFrancesco Marrosu
Sep 21, 2018·Frontiers in Cellular Neuroscience·Tanya McDonaldKarin Borges
Nov 23, 2018·Epilepsy Currents·Manisha Patel
Sep 26, 2020·Molecular Neurobiology·Igor Santana de MeloOlagide Wagner de Castro
Oct 31, 2020·Molecular Neurobiology·Igor Santana de MeloOlagide Wagner de Castro
Jun 7, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tanveer SinghRajesh Kumar Goel

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Methods Mentioned

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nuclear magnetic resonance

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