Age-Dependent Biochemical Dysfunction in Skeletal Muscle of Triple- Transgenic Mouse Model of Alzheimer`s Disease

Author(s): Vera F. Monteiro-Cardoso, Marisa Castro, M.M. Oliveira, Paula I. Moreira, Francisco Peixoto, Romeu A. Videira.

Journal Name: Current Alzheimer Research

Volume 12 , Issue 2 , 2015

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Abstract:

The emergence of Alzheimer`s disease as a systemic pathology shifted the research paradigm toward a better understanding of the molecular basis of the disease considering the pathophysiological changes in both brain and peripheral tissues. In the present study, we evaluated the impact of disease progression on physiological relevant features of skeletal muscle obtained from 3, 6 and 12 month-old 3xTg-AD mice, a model of Alzheimer`s disease, and respective agematched nonTg mice. Our results showed that skeletal muscle functionality is already affected in 3-month-old 3xTg-AD mice as evidenced by deficient acetylcholinesterase and catalase activities as well as by alterations in fatty acid composition of mitochondrial membranes. Additionally, an age-dependent accumulation of amyloid-β1-40 peptide occurred in skeletal muscle of 3xTg-AD mice, an effect that preceded bioenergetics mitochondrial dysfunction, which was only detected at 12 months of age, characterized by decreased respiratory control ratio and ADP/O index and by an impairment of complex I activity. HPLC-MS/MS analyses revealed significant changes in phospholipid composition of skeletal muscle tissues from 3xTg-AD mice with 12 months of age when compared with age-matched nonTg mice. Increased levels of lyso-phosphatidylcholine associated with a decrease of phosphatidylcholine molecular species containing arachidonic acid were detected in 3xTg-AD mice, indicating an enhancement of phospholipase A2 activity and skeletal muscle inflammation. Additionally, a decrease of phosphatidylethanolamine plasmalogens content and an increase in phosphatidylinositol levels was observed in 3xTg-AD mice when compared with age-matched nonTg mice. Altogether, these observations suggest that the skeletal muscle of 3xTg-AD mice are more prone to oxidative and inflammatory events.

Keywords: Alzheimer’s disease, amyloid-β, lipidomics, mitochondrial bioenergetics, phospholipase A2, phospholipids, skeletal muscle.

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Article Details

VOLUME: 12
ISSUE: 2
Year: 2015
Page: [100 - 115]
Pages: 16
DOI: 10.2174/1567205012666150204124852

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