Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease.
J Alzheimers Dis
; 27(4): 853-69, 2011.
Article
em En
| MEDLINE
| ID: mdl-21914946
ABSTRACT
Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) reduces amyloid-ß (Aß) and tau pathology and improves cognitive performance in animal models of Alzheimer's disease (AD). To exclude confounding variables associated with the diet, we crossed 3 × Tg-AD mice (modeling AD neuropathology) with transgenic Fat-1 mice that express the fat-1 gene encoding a PUFA desaturase, which endogenously produces n-3 PUFA from n-6 PUFA. The expression of fat-1 shifted the n-3n-6 PUFA ratio upward in the brain (+11%, p < 0.001), including docosahexaenoic acid (DHA; +5%, p < 0.001) in 20 month-old mice. The expression of fat-1 decreased the levels of soluble Aß42 (-41%, p < 0.01) at 20 months without reducing the level of insoluble forms of Aß40 and Aß42 in the brain of 3 × Tg-AD mice. The 3 × Tg-AD/Fat-1 mice exhibited lower cortical levels of both soluble (-25%, p < 0.05) and insoluble phosphorylated tau (-55%, p < 0.05) compared to 3 × Tg-AD mice, but only in 20 month-old animals. Whereas a decrease of calcium/calmodulin-dependent protein kinase II was observed in 3 × Tg-AD/Fat-1 mice (-039%, p < 0.05), altered tau phosphorylation could not be related to changes in glycogen synthase kinase 3ß, cyclin-dependent kinase 5, or protein phosphatase type 2A enzymatic activity. In addition, the expression of the fat-1 transgene prevented the increase of glial fibrillary acidic protein (-37%, p < 0.01) observed in 20 month-old 3 × Tg-AD mice. In conclusion, the expression of fat-1 in 3 × Tg-AD mice increases brain DHA and induces biomarker changes that are consistent with a beneficial effect against an AD-like neuropathology.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Ácidos Graxos Ômega-3
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Ácidos Graxos Ômega-6
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article