title: Early mitochondrial dysfunction occurs in motor cortex and spinal cord at the onset of disease in the Wobbler mouse.
abstract: The Wobbler mouse is recognized as an animal model for motoneuron disease that exhibits motoneuron pathology. We have recently demonstrated the occurrence of mitochondrial dysfunction in the Wobbler mouse brain. The aim of the present study was to evaluate whether mitochondrial dysfunction occurred at an early age at the time where disease symptoms appear, and whether it was more pronounced in the motor cortex or in the spinal cord. We report here a significant decrease in mitochondrial state 3 and 4 respiration rates at an early age in the Wobbler spinal cord. In addition, there was a pronounced decrease in oxidative phosphorylation in mitochondria isolated from both spinal cord and motor cortex in both age groups. This mitochondrial dysfunction was accompanied by impairment of complex I activity in mitochondria isolated from spinal cord at an early age. Decreases in complex III and IV activities were observed only in mitochondria isolated from the motor cortex at an early age, but impairment of complex III activity prevailed until later in the disease. We conclude that mitochondrial dysfunction ensues at an early stage of the disease and is more pronounced in the spinal cord, which correlates with previous studies that reported degeneration of spinal cord motorneurons.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, Miami, FL 33101, USA.
authors.forename: Kunjan R
authors.initials: KR
authors.lastname: Dave
authors.forename: Walter G
authors.initials: WG
authors.lastname: Bradley
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pérez-Pinzón
mesh_terms: D000367:Age Factors; D000818:Animals; D019069:Cell Respiration / Q000235:genetics; D018450:Disease Progression; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D009044:Motor Cortex / Q000737:chemistry / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics; D010641:Phenotype; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III