Mitochondrial dysfunction in mouse trisomy 16 brain.
Mitochondrial function in the brain of mouse trisomy 16, an animal model of Down syndrome with accelerated neuron death, was studied in isolated cortex mitochondria. Using an oxygen-sensitive Clarke electrode, a selective 16% decrease in respiration was detected with the Complex I substrates malate and glutamate but not with the Complex II substrate succinate. Western blotting revealed a 20% decrease in the 20 kDa subunit of Complex I in Ts16 brain cortex homogenates with no significant decrease in marker proteins for the other complexes of the electron transport chain. Although no differences in H(2)O(2) production or maximal calcium uptake were detected in the Ts16 mitochondria, there was an 18% decrease in pyruvate dehydrogenase levels, a change associated with oxidative stress in ischemia. These results are similar to those found in Parkinson's disease suggesting some neurodegenerative diseases may have mitochondrial pathology as a common step.
Department of Anesthesiology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA. lbambric@umaryland.edu
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D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D019069:Cell Respiration / Q000235:genetics; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000235:genetics; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics / Q000378:metabolism; D014314:Trisomy / Q000235:genetics* / Q000503:physiopathology
D011768:Pyruvate Dehydrogenase Complex; D042967:Electron Transport Complex I