Project description:Kurozu is a traditional Japanese rice vinegar. During fermentation and aging of the Kurozu liquid in an earthenware jar over 1 year, solid residue called Kurozu Moromi is produced. In the present study, we evaluated whether concentrated Kurozu or Kurozu Moromi could ameliorate cognitive dysfunction in the senescence accelerated P8 mouse. Senescence accelerated P8 mice were fed 0.25% (w/w) concentrated Kurozu or 0.5% (w/w) Kurozu Moromi for 4 or 25 weeks. Kurozu suppressed cognitive dysfunction and amyloid accumulation in the brain, while Kurozu Moromi showed a tendency to ameliorate cognitive dysfunction, but the effect was not significant. We hypothesize that concentrated Kurozu has an antioxidant effect, however, the level of lipid peroxidation in the brain did not differ in senescence accelerated P8 mice. DNA microarray analysis indicated that concentrated Kurozu increased HSPA1A mRNA expression, a protein that prevents protein misfolding and aggregation. The increase in HSPA1A expression by Kurozu was confirmed using quantitative real-time PCR and immunoblotting methods. Therefore, the suppression of amyloid accumulation by concentrated Kurozu may be associated with HSPA1A induction. However, concentrated Kurozu could not increase HSPA1A expression in mouse primary neurons, suggesting it may not directly affect neurons. Ten-times concentrated Kurozu (CK) was made from Kurozu liquid (Sakamoto Kurozu, Fukuyama, Kagoshima, Japan) by repeated vacuum distillation. The CK diet included 0.25% (w/w) CK in CE-2 basic rodent diet (Nihon CLEA, Tokyo, Japan). Senescence resistance (R1) and senescence accelerated P8 (P8) mice were purchased from Japan SLC (Shizuoka, Japan). Mice were housed at 25Â±2Â°C with 55Â±10% humidity on a 12-h light/dark cycle (lighting time 08:00-20:00). All mice were housed in independent cages and had free access to food and water. All procedures were compliant with the guidelines of the Kagoshima University Animal Ethics Committee (A10030). Ten-week old R1 mice (n=16) were fed a control CE2 diet and P8 mice were divided into three groups as follows: control CE2 diet group (n=9), KM diet group (n=9) or CK diet group (n=9). Feeding of the experimental diet started from 12 weeks of age until sacrificed. All mice were sacrificed under anesthesia at 17 weeks old (4 months old). The left side of the hippocampus region was excised from brains of 4 mice selected at random in each group, and then subjected to microarray analysis.

Project description:Background: Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and hippocampus in two rare inbred mouse models of accelerated neurological senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J). Results: The majority of age-related gene expression changes were strain-specific, with only a few common pathways found for normal and accelerated neurological aging. Polymorphism screening led to the identification of mutations that could have a direct impact on important disease processes, including a mutation in a fibroblast growth factor gene, Fgf1, and a mutation in and ectopic expression of the gene for the chemokine CCL19, which is involved in the inflammatory response. Conclusions: We show that combining the study of inbred mouse strains with interesting traits and gene-expression profiling can lead to the discovery of genes important for complex phenotypes. Furthermore, full-genome polymorphism detection, sequencing and gene-expression profiling of inbred mouse strains with interesting phenotypic differences may provide unique insights into the molecular genetics of late-manifesting complex diseases. Experiment Overall Design: Gene-expression profiling was performed on 3 month-old (young), 16 month-old (old) S8, S10 and SR1 mice. Two independent samples for each time point were used in gene-expression profiling for each strain. Because of greater replicate variability, three samples were used for hippocampus of 16-month SAM mice. A 10.0 ug sample of total RNA was used to generate labeled cRNA for each sample according to recommended protocols (Affymetrix). RNA from multiple animals was not pooled, except in the case of retina, where the retinas of two mice were combined to generate sufficient total RNA.

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Mus strain:SAMP and SAMR

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