title: Mitochondrial oxygen consumption deficits in skeletal muscle isolated from an Alzheimer's disease-relevant murine model.
abstract: BACKGROUND
  Age is considered a primary risk factor for neurodegenerative diseases including Alzheimer's disease (AD). It is also now well understood that mitochondrial function declines with age. Mitochondrial deficits have been previously assessed in brain from both human autopsy tissue and disease-relevant transgenic mice. Recently it has been recognized that abnormalities of muscle may be an intrinsic aspect of AD and might contribute to the pathophysiology. However, deficits in mitochondrial function have yet to be clearly assessed in tissues outside the central nervous system (CNS). In the present study, we utilized a well-characterized AD-relevant transgenic mouse strain to assess mitochondrial respiratory deficits in both brain and muscle. In addition to mitochondrial function, we assessed levels of transgene-derived amyloid precursor protein (APP) in homogenates isolated from brain and muscle of these AD-relevant animals.
  
  
  RESULTS
  We now demonstrate that skeletal muscles isolated from these animals have differential levels of mutant full-length APP depending on muscle type. Additionally, isolated muscle fibers from young transgenic mice (3 months) have significantly decreased maximal mitochondrial oxygen consumption capacity compared to non-transgenic, age-matched mice, with similar deficits to those previously described in brain.
  
  
  CONCLUSIONS
  This is the first study to directly examine mitochondrial function in skeletal muscle from an AD-relevant transgenic murine model. As with brain, these deficits in muscle are an early event, occurring prior to appearance of amyloid plaques.
authors: Research Service, VAMHCS, 10 North Greene Street, 3C-125, Baltimore, Maryland 21201, USA. rschu003@umaryland.edu.
authors: Rosemary A
authors: RA
authors: Schuh
authors: Kathryn C
authors: KC
authors: Jackson
authors: Anna E
authors: AE
authors: Schlappal
authors: Espen E
authors: EE
authors: Spangenburg
authors: Christopher W
authors: CW
authors: Ward
authors: Ji H
authors: JH
authors: Park
authors: Natalie
authors: N
authors: Dugger
authors: Guo Li
authors: GL
authors: Shi
authors: Paul S
authors: PS
authors: Fishman
mesh_terms: D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption
chemical_list: D010100:Oxygen