title: Cell-specific modulation of monocarboxylate transporter expression contributes to the metabolic reprograming taking place following cerebral ischemia.
abstract: Monocarboxylate transporters (MCTs) are involved in lactate trafficking and utilization by brain cells. As lactate is not only overproduced during ischemia but its utilization was shown to be essential upon recovery, we analyzed the expression of the main cerebral MCTs at 1 and 24h after an ischemic insult induced by a transient occlusion of the left middle cerebral artery (MCAO) in CD1 mice (n=5, 7 and 10 for control, 1 and 24h groups, respectively). After 1h of reperfusion, an upregulation of the three MCTs was observed in the striatum (MCT1 ipsilateral 2.73 ± 0.2 and contralateral 2.01 ± 0.4; MCT2 ipsilateral 2.1 ± 0.1; MCT4 ipsilateral 1.65 ± 0.1) and in the surrounding cortex of both the ipsilateral (MCT1 2.4 ± 0.4; MCT2 1.62 ± 0.2; MCT4 1.31 ± 0.1) and contralateral (MCT1 2.78 ± 0.4; MCT2 1.76 ± 0.2) hemispheres, compared to the corresponding sham hemispheres. An increase of MCT1 (ipsilateral 2.1 ± 0.2) and MCT2 (contralateral 1.9 ± 0.1) expression was also observed in the hippocampus, while no effect was observed for MCT4. At 24h of reperfusion, total MCT2 and MCT4 expressions were decreased in the striatum (MCT2 ipsilateral 0.32 ± 0.1 and contralateral 0.63 ± 0.1; MCT4 ipsilateral 0.59 ± 0.1) and the surrounding cortex (MCT4 ipsilateral 0.67 ± 0.1), compared to the sham. At the cellular level, neurons which usually express only MCT2 strongly expressed MCT1 at both time points. Surprisingly, staining for MCT4 appeared on neurons and was strong at 24h post-insult, in the striatum and the cortex of both hemispheres. A similar expression pattern was observed also in the ipsilateral hemisphere of the sham operated animals at 24h. Overall, our study indicates that cell-specific changes in MCT expression induced by an ischemic insult may participate to the metabolic adaptations taking place in the brain after a transient ischemic episode.
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland. Electronic address: katia.rosafio@unil.ch.
authors.forename: K
authors.initials: K
authors.lastname: Rosafio
authors.affiliation: Department of Clinical Neurosciences, Neurology Service, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address: ximena.castillo@unil.ch.
authors.forename: X
authors.initials: X
authors.lastname: Castillo
authors.affiliation: Department of Clinical Neurosciences, Neurology Service, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address: lorenz.hirt@unil.ch.
authors.forename: L
authors.initials: L
authors.lastname: Hirt
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland. Electronic address: luc.pellerin@unil.ch.
authors.forename: L
authors.initials: L
authors.lastname: Pellerin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D007839:Functional Laterality; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D015424:Reperfusion; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D008869:Microtubule-Associated Proteins; D027501:Monocarboxylic Acid Transporters; C079240:Mtap2 protein, mouse; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse; D010751:Phosphopyruvate Hydratase
keywords: astrocyte; ischemia; microvessel; monocarboxylate transporter; neuron