Journal
NEUROMOLECULAR MEDICINE
Volume 16, Issue 4, Pages 669-685Publisher
HUMANA PRESS INC
DOI: 10.1007/s12017-014-8317-7
Keywords
Oxidative stress; Polyunsaturated fatty acid; DNA repair response; Gender dimorphism; Lipid peroxidation
Categories
Funding
- Spanish Ministry of Science and Innovation [CENIT Program] [BFU2009-11879/BFI, AGL2006-1243]
- Autonomous Goverment of Catalunya [2009SGR-735]
- Spanish Ministry of Health [FIS 08-1843, 11-01532, FIS13-00584]
- COST Action [B-35]
- Fundacio Miquel Valls
- Autonomous Government of Catalonia
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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 gamma H2AX 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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