Mitochondrial oxygen consumption deficits in skeletal muscle isolated from an Alzheimer’s disease-relevant murine model
1 Research Service, VAMHCS, 10 North Greene Street, 3C-125, Baltimore, Maryland 21201, USA
2 Neurology Service, VAMHCS, Baltimore, Maryland 21201, USA
3 Department of Neurology, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA
4 University of Maryland School of Public Health, Department of Kinesiology, College Park, Maryland 20742, USA
5 Program in Neuroscience and Cognitive Sciences, University of Maryland, College Park, Maryland 20742, USA
6 University of Maryland, BioMet and School of Nursing, Baltimore, Maryland 21201, USA
7 Present address: Department of Nutrition and Food Science, University of Maryland, College Park, Maryland 20742, USA
BMC Neuroscience 2014, 15:24 doi:10.1186/1471-2202-15-24Published: 13 February 2014
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.
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.
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.