title: Dietary lipid unsaturation influences survival and oxidative modifications of an amyotrophic lateral sclerosis model in a gender-specific manner.
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.
authors: NUTREN-Nutrigenomics, Institut de Recerca Biomèdica de Lleida-Universitat de Lleida, Av. Rovira Roure 80, 25198, Lleida, Spain.
authors: Daniel
authors: D
authors: Cacabelos
authors: Victoria
authors: V
authors: Ayala
authors: Omar
authors: O
authors: Ramírez-Nunez
authors: Ana Belen
authors: AB
authors: Granado-Serrano
authors: Jordi
authors: J
authors: Boada
authors: Jose C E
authors: JC
authors: Serrano
authors: Rosanna
authors: R
authors: Cabré
authors: Gisela
authors: G
authors: Nadal-Rey
authors: Maria Josep
authors: MJ
authors: Bellmunt
authors: Isidro
authors: I
authors: Ferrer
authors: Reinald
authors: R
authors: Pamplona
authors: Manuel
authors: M
authors: Portero-Otin
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D005224:Fats, Unsaturated / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D005609:Free Radicals; D006031:Glycosylation / Q000187:drug effects; D006657:Histones / Q000032:analysis; D007249:Inflammation; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration; D018384:Oxidative Stress / Q000187:drug effects; D017354:Point Mutation; D050050:Protein Carbonylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012727:Sex Characteristics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D004041:Dietary Fats; D005224:Fats, Unsaturated; D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D006657:Histones; D011993:Recombinant Fusion Proteins; C475961:gamma-H2AX protein, mouse; D000080242:8-Hydroxy-2'-Deoxyguanosine; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003849:Deoxyguanosine