Elevated oxidative stress in the brain of senescence-accelerated mice at 5 months of age.
The senescence-accelerated mouse (SAM) is a useful animal model to study aging or age-associated disorder. In the present study, we have used a multidisciplinary approach to the characterization of changes that occur in aging and in the modelling of brain aging. The SAMP8 mouse at 5 months of age exhibited an increase in gliosis and molecular oxidative damage. Likewise, we found that superoxide dismutase activity decreased compared with age-matched SAMR1 while there were no differences in activity of catalase and glutathione reductase. These results indicate that the decrease of superoxide dismutase may be involved in the increase of oxidative stress in brain of SAMP8 at younger stages. This suggestion is supported by an increase in the expression of alpha-synuclein together with phosphorylated tau protein, which is concurrent with the decline of that antioxidant enzyme. Alpha-synuclein aggregates are invariably associated with tau pathologies and our results demonstrate that alpha-synuclein accumulation is a potent inducer of tau pathologies not only in neurodegenerative diseases but also in normal aging. These results also imply that SAMP8 are exposed to elevated levels of oxidative stress from an early age, and that could be a very important cause of the senescence-related impairments and degeneration in the brain seen in this strain.
Alvarez-García
Oscar
O
Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, C/ Julián Clavería s/n, Oviedo, 33006, Spain.
Vega-Naredo
Ignacio
I
Sierra
Verónica
V
Caballero
Beatriz
B
Tomás-Zapico
Cristina
C
Camins
Antonio
A
García
José Joaquín
JJ
Pallàs
Mercè
M
Coto-Montes
Ana
A
D000375:Aging / Q000378:metabolism*; D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008818:Mice, Neurologic Mutants; D023421:Models, Animal; D018384:Oxidative Stress; D010766:Phosphorylation; D013482:Superoxide Dismutase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
D000975:Antioxidants; D051844:alpha-Synuclein; D016875:tau Proteins; D013482:Superoxide Dismutase