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Published byEsko Järvenpää Modified over 6 years ago
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High-fat diet increases tau expression in the brain of T2DM and AD mice independently of peripheral metabolic status Mari Takalo, Annakaisa Haapasalo, Henna Martiskainen, Kaisa M.A. Kurkinen, Henna Koivisto, Pasi Miettinen, Vinoth K.M. Khandelwal, Susanna Kemppainen, Dorota Kaminska, Petra Mäkinen, Ville Leinonen, Jussi Pihlajamäki, Hilkka Soininen, Markku Laakso, Heikki Tanila, Mikko Hiltunen Journal of Nutritional Biochemistry Volume 25, Issue 6, Pages (June 2014) DOI: /j.jnutbio Copyright © 2014 Elsevier Inc. Terms and Conditions
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Fig. 1 High-fat diet increases 4R- and 3R-tau expression and tau exon 10 inclusion. (A) Protein lysates extracted from the temporal cortex of female mice fed with STD or TWD were analyzed with Western blotting using antibodies specific for 4R- and 3R-tau isoforms. The levels were normalized to those of GAPDH in the same samples. The intensity of ~52 kDa band, which is similar in the size as the 0N4R-tau isoform in the control sample (HEK293 cells over-expressing 0N4R-tau, first lane), was increased in all mice fed with TWD. (B) Quantitative PCR combined with capillary electrophoresis was used to analyze the mRNA levels of 3R- and 4R-tau from the same cortical samples. Expression levels in wild-type (AwIw) mice on STD were set to 100%. Mean values±S.E.M. are shown, n=4–6 mice/group, ****P≤.0001. Journal of Nutritional Biochemistry , DOI: ( /j.jnutbio ) Copyright © 2014 Elsevier Inc. Terms and Conditions
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Fig. 2 High-fat diet-induced tau expression and tau exon 10 inclusion phenotype do not associate with astrogliosis. (A) Protein lysates extracted from the temporal cortex of female mice fed with STD or TWD diet were analyzed by Western blotting using GFAP-specific antibody. GFAP levels were normalized to those of GAPDH. Protein lysate from HEK293 cells overexpressing the 0N4R-tau isoform (0N4R) was used as control on the Western blot gels. HEK293 cells do not express GFAP. qPCR was used to determine the GAPDH-normalized mRNA levels of (B) TNFα and (C) IL1β from the RNA samples extracted from the ventral cortex of female mice. TNFalpha and IL1beta protein levels were measured using ELISA. A significant diet effect on TNFα levels was found in mice fed with TWD. Levels in wild-type (AwIw) mice on STD were set to 100%. Mean values ± S.E.M. are shown, n=4–6 mice/group, *P<.05. Journal of Nutritional Biochemistry , DOI: ( /j.jnutbio ) Copyright © 2014 Elsevier Inc. Terms and Conditions
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Fig. 3 High-fat diet does not affect the mRNA levels of splicing factors involved in the tau exon 10 inclusion. Quantitative PCR was used to analyze the mRNA expression levels of tau exon 10 splicing factors (A) Tra2β, (B) SC35, (C) SRp30s and (D) SF2/ASF in the temporal cortex of female mice on STD or TWD. The mRNA levels were normalized to those of GAPDH. Values in wild-type (AwIw) mice on STD were set to 100 %. Mean values ± S.E.M. are shown, n=4–6 mice/group. Journal of Nutritional Biochemistry , DOI: ( /j.jnutbio ) Copyright © 2014 Elsevier Inc. Terms and Conditions
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Fig. 4 Expression levels of tau and TNFα correlate with behavior. (A) Correlation between relative 4R-tau expression in the temporal cortex and search bias during the last trial of the Morris swim task, a measure of spatial memory retention. The different treatment groups are indicated with symbols. For instance, AwIwS=APdE9 wild-type, IGF2 wild-type, standard diet; A+I+T=APdE9 transgenic, IGF2 transgenic, typical Western (high-fat) diet. (B) Correlation between relative TNFα expression and gross horizontal distance (ambulatory distance) traversed in the TruScan test. Journal of Nutritional Biochemistry , DOI: ( /j.jnutbio ) Copyright © 2014 Elsevier Inc. Terms and Conditions
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