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Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease.
J Alzheimers Dis 2011; 27(4):853-69JA

Abstract

Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) reduces amyloid-β (Aβ) 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-3:n-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 Aβ₄₂ (-41%, p < 0.01) at 20 months without reducing the level of insoluble forms of Aβ₄₀ and Aβ₄₂ 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 3β, 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.

Authors+Show Affiliations

Faculty of Pharmacy, Laval University, Quebec, QC, Canada.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21914946

Citation

Lebbadi, Meryem, et al. "Endogenous Conversion of Omega-6 Into Omega-3 Fatty Acids Improves Neuropathology in an Animal Model of Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 27, no. 4, 2011, pp. 853-69.
Lebbadi M, Julien C, Phivilay A, et al. Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease. J Alzheimers Dis. 2011;27(4):853-69.
Lebbadi, M., Julien, C., Phivilay, A., Tremblay, C., Emond, V., Kang, J. X., & Calon, F. (2011). Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 27(4), pp. 853-69. doi:10.3233/JAD-2011-111010.
Lebbadi M, et al. Endogenous Conversion of Omega-6 Into Omega-3 Fatty Acids Improves Neuropathology in an Animal Model of Alzheimer's Disease. J Alzheimers Dis. 2011;27(4):853-69. PubMed PMID: 21914946.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous conversion of omega-6 into omega-3 fatty acids improves neuropathology in an animal model of Alzheimer's disease. AU - Lebbadi,Meryem, AU - Julien,Carl, AU - Phivilay,Alix, AU - Tremblay,Cyntia, AU - Emond,Vincent, AU - Kang,Jing X, AU - Calon,Frédéric, PY - 2011/9/15/entrez PY - 2011/9/15/pubmed PY - 2012/4/17/medline SP - 853 EP - 69 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 27 IS - 4 N2 - Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) reduces amyloid-β (Aβ) 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-3:n-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 Aβ₄₂ (-41%, p < 0.01) at 20 months without reducing the level of insoluble forms of Aβ₄₀ and Aβ₄₂ 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 3β, 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/21914946/Endogenous_conversion_of_omega_6_into_omega_3_fatty_acids_improves_neuropathology_in_an_animal_model_of_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JAD-2011-111010 DB - PRIME DP - Unbound Medicine ER -