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Radial arm water maze data and rotarod performance were analyzed by repeated-measures analysis of variance (ANOVA) to assess the overall effect of diet. For the radial arm water maze data, we also performed Student��s t-test on individual block data. For gene expression analysis, we used the Mann�CWhitney�CWilcoxon test. For other data, one-way ANOVA and Student��s t-test were performed. Statistical significance was assigned when the P-value was buy BGB324 from 6 to 12?months of age, resulted in significant elevations in plasma homocysteine levels in both WT and APP/PS1 transgenic mice (WT control: 6.85��0.8?��mol/L, WT HHcy: 68.23��12.1?��mol/L, APP/PS1 control: 7.65��1.4?��mol/L and APP/PS1 HHcy: 64.21��8.3?��mol/L). There was no significant difference between WT and APP/PS1 transgenic mice in the plasma homocysteine levels induced by the diet. In C57BL/6 mice, normal homocysteine levels are considered to be 5 to 12?��mol/L. Hyperhomocysteinemia can be categorized as mild (12 to 30?��mol/L), moderate (30 to 100?��mol/L) or severe (>100?��mol/L) [20]. SCH727965 On the basis of the levels we observed in our experimental mice, HHcy levels were moderate. None of our mice reached the plasma level of homocysteine classified as severe HHcy. In the 2-day radial arm water maze task, WT mice began the test na?ve and made an average of five errors per trail (Figure?1). The WT control mice were making less than one error per trail by the end of the first day, and this performance continued into day 2. HHcy WT mice were impaired in performing the task and were significantly impaired compared to WT control mice throughout the second day of testing (PRamoplanin HHcy APP/PS1 transgenic mice showed more severe impairment, with an apparent additive effect of HHcy combined with the APP/PS1 transgene (P