Dietary Lipid Unsaturation Influences Survival and Oxidative Modifications of an Amyotrophic Lateral Sclerosis Model in a Gender-Specific Manner
Male
Glycosylation
DNA Repair
Free Radicals
Gender dimorphism
DNA, Mitochondrial
Histones
Mice
03 medical and health sciences
Animals
Inflammation
0303 health sciences
Amyotrophic Lateral Sclerosis
Deoxyguanosine
Dietary Fats
Fats, Unsaturated
3. Good health
Disease Models, Animal
Polyunsaturated fatty acid
DNA repair response
Oxidative stress
8-Hydroxy-2'-Deoxyguanosine
Fatty Acids, Unsaturated
Female
Lipid Peroxidation
Biomarkers
DNA Damage
DOI:
10.1007/s12017-014-8317-7
Publication Date:
2014-07-01T09:22:14Z
AUTHORS (12)
ABSTRACT
The implication of lipid peroxidation in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) derive from high abundance of peroxidation-prone polyunsaturated fatty acids in central nervous system and its relatively low antioxidant content. In the present work, we evaluated the effect of dietary changes aimed to modify fatty acid tissular composition in survival, disease onset, protein, and DNA oxidative modifications in the hSODG93A transgenic mice, a model of this motor neuron disease. Both survival and clinical evolution is dependent on dietary fatty acid unsaturation and gender, with high unsaturated diet, leading to loss of the disease-sparing effect of feminine gender. This was associated with significant increases in protein carbonyl and glycoxidative modifications as well as non-nuclear 8-oxo-dG, a marker of mitochondrial DNA oxidation. Comparison of these data with γH2AX immunostaining, a marker of DNA damage response, suggests that the highly unsaturated diet-blunted mitochondrial-nuclear free radical dependent crosstalk, since increased 8-oxo-dG was not correlated with increased DNA damage response. Paradoxically, the highly unsaturated diet led to lower peroxidizability but higher anti-inflammatory indexes. To sum up, our results demonstrate that high polyunsaturated fatty acid content in diets may accelerate the disease in this model. Further, these results reinforce the need for adequately defining gender as a relevant factor in ALS models, as well as to use structurally characterized markers for oxidative damage assessment in neurodegeneration.
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CITATIONS (12)
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