Effect of Kurozu on hippocampal gene expression profiles in SAMP8
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE70514 | GEO | 2016/03/11
SECONDARY ACCESSION(S): PRJNA288938
REPOSITORIES: GEO
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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 25±2°C with 55±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.
2016-03-11 | E-GEOD-70514 | biostudies-arrayexpress
Project description:The prevention or delay of brain senescence would enhance the quality of life for older persons. We investigated the effects of soybean extracts in senescence-accelerated (SAMP10) mice. This mouse is a model of brain senescence with a short life span, cerebral atrophy and cognitive dysfunction. Mice were fed a diet containing soybean extracts from 1 to 12 months of age. The effects of green and yellow soybean extracts were compared with a control diet without soybean extracts. Cognitive functions were higher in aged mice fed green soybean than age-matched control mice and mice fed yellow soybean. We further investigated transcriptome of the SAMP10 hippocampus indicated that expression levels of 36 genes were significantly higher and 19 genes were lower in mice that ingested green soybean than in mice that ingested yellow soybean. Some of the evidences were reconfirmed by real time PCR analysis; the levels of Cdh1 and Ptgds mRNA were significantly higher and that the level of Aplp1 was significantly lower in aged SAMP10 mice fed green soybean than mice ingested yellow soybean and control mice. Additionally, the amount of amyloid beta 40 and 42 was lower in the insoluble fraction of aged SAMP10 mice fed green soybean than control mice and mice fed yellow soybean, although the levels of amyloid beta 40 and 42 in the soluble fraction were not different. Lipocalin-type prostaglandin D2 synthase (L-PGDS) has been proposed as the endogenous amyloid beta - chaperone, suggesting that amyloid aggregation was lower in mice fed green soybean than control mice and mice fed yellow soybean. These results indicate that the intake of green soybean improved cognitive function in aged mice, and suppressed amyloid beta accumulation. Green soybean might help healthy aging of the brain in older persons. The effect of green and yellow soybean extracts on cognitive function in aged SAMP10 mice. Mice were fed a CE-2 diet containing 3.0% soybean extracts taken from both yellow and green soybean species, from 1 to 12 months of age. Total RNA was extracted from the stored hippocampus for DNA microarray analysis.
2014-06-26 | E-GEOD-58811 | biostudies-arrayexpress
Project description:The prevention or delay of brain senescence would enhance the quality of life for older persons. We investigated the effects of soybean extracts in senescence-accelerated (SAMP10) mice. This mouse is a model of brain senescence with a short life span, cerebral atrophy and cognitive dysfunction. Mice were fed a diet containing soybean extracts from 1 to 12 months of age. The effects of green and yellow soybean extracts were compared with a control diet without soybean extracts. Cognitive functions were higher in aged mice fed green soybean than age-matched control mice and mice fed yellow soybean. We further investigated transcriptome of the SAMP10 hippocampus indicated that expression levels of 36 genes were significantly higher and 19 genes were lower in mice that ingested green soybean than in mice that ingested yellow soybean. Some of the evidences were reconfirmed by real time PCR analysis; the levels of Cdh1 and Ptgds mRNA were significantly higher and that the level of Aplp1 was significantly lower in aged SAMP10 mice fed green soybean than mice ingested yellow soybean and control mice. Additionally, the amount of amyloid beta 40 and 42 was lower in the insoluble fraction of aged SAMP10 mice fed green soybean than control mice and mice fed yellow soybean, although the levels of amyloid beta 40 and 42 in the soluble fraction were not different. Lipocalin-type prostaglandin D2 synthase (L-PGDS) has been proposed as the endogenous amyloid beta - chaperone, suggesting that amyloid aggregation was lower in mice fed green soybean than control mice and mice fed yellow soybean. These results indicate that the intake of green soybean improved cognitive function in aged mice, and suppressed amyloid beta accumulation. Green soybean might help healthy aging of the brain in older persons.
2014-06-26 | GSE58811 | GEO
Project description:Aging leads to a progressive deterioration in brain function, which will eventually result in cognitive decline and can develop into a dementia. The mechanisms underlying pathological cognitive decline in aging are still poorly understood. The peripheral immune system, as well as the meningeal lymphatic vasculature and the immune cells residing in the brain and meninges, are all affected by aging. Moreover, recent studies have linked the dysfunction of the meningeal lymphatic system and peripheral immunity to accelerated brain aging. We hypothesized that an age-related reduction in CCR7-dependent immune cell egress through the lymphatic vasculature mediates some aspects of aging-associated brain dysfunction, leading to cognitive decline and potentially exacerbating neurodegenerative diseases. Here, we report a reduction in CCR7 expression by meningeal T cells in aged mice and its associated increase in meningeal T-regulatory cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to cognitive impairment. Interestingly, CCR7-deficient mice also presented impaired brain glymphatic function and showed increased amyloid beta (A) deposition when crossed with the 5xFAD transgenic mouse model of Alzheimer’s disease (AD). These results show that the aging-associated decrease in CCR7 expression impacts meningeal immunity, affects different aspects of brain function and exacerbates brain A pathology, highlighting its potential as a pathogenic mechanism for cognitive decline in aging and AD.
2021-03-22 | GSE163725 | GEO
Project description:Thiazolidinediones (TZDs) are agonists at peroxisome proliferator-activated gamma-type (PPAR-y) receptors and are used clinically for the treatment of type 2 diabetes where they have been shown to reestablish insulin sensitivity, improve lipids profile, and reduce inflammation. Recent work also suggests that TZDs may be beneficial in Alzheimer's disease (AD), ameliorating cognitive decline early in the disease process. However, there have been only a few studies identifying mechanisms through which cognitive benefits may be exerted. Starting at 10 months of age, the triple transgenic mouse model of AD (3xTg-AD) with accelerated amyloid-B (AB) deposition and tau pathology was treated with the TZD pioglitazone (PIO- Actos) at 18 mg/Kg body weight/day. After four months, PIO-treated animals showed multiple beneficial effects, including improved learning on the active avoidance task, reduced serum cholesterol, decreased hippocampal AB deposits, and enhanced short- and long-term plasticity. Baseline electrophysiological membrane properties and blood glucose levels were unchanged by PIO treatment. Gene microarray analyses of hippocampal tissue identified predicted transcriptional responses following TZD treatment as well as potentially novel targets of TZDs, including facilitation of estrogenic processes, and decreases in glutamatergic and ketone metabolic/ cholesterol dependent processes. Taken together, these results confirm prior animal studies showing that TZDs can ameliorate cognitive deficits associated with AD-related pathology, but also extend these findings by pointing to novel molecular targets in the brain. Keywords : Hippocampus; LTP; Microarray analysis; Avoidance learning; Aging; PPAR; Synaptic hyperpolarization; T2DM We used the 3xTg-AD mouse model of Alzheimer's disease and monitored the effects of pioglitazone (PIO-Actos a TZD) on behavioral, electrophysiological, and molecular variables. Emphasis was placed on identifying hippocampal PIO-sensitive genes that were also associated with learning and memory processes. Starting at 10 months of age, female mice were treated for approximately 14 weeks with either a control diet or a PIO-containing diet. PIO was incorporated into the diet to yield a final dose of approximately 18 mg/kg body weight/day.
2012-04-12 | E-GEOD-32536 | biostudies-arrayexpress
Project description:Sirtuin 3 (SIRT3) is an NAD+-dependent deacetylase involved in various physiological and pathological processes. However, the role of SIRT3 in regulating human stem cell senescence remains largely unknown. Here, we observed the downregulated expression of SIRT3 in senescent human mesenchymal stem cells (hMSCs). SIRT3 deficiency accelerated cellular senescence in hMSCs, along with compromised nuclear integrity, loss of heterochromatin and increased DNA damage. These aging-associated nuclear defects were attenuated by the reintroduction of SIRT3. Mechanistic studies demonstrated the interaction of SIRT3 with nuclear envelope proteins and heterochromatin-associated proteins. Further findings revealed that SIRT3 deficiency led to the loss of lamina-associated domains (LADs) from the nuclear lamina, increased chromatin accessibility and aberrant transcription of repetitive sequences. Meanwhile, the overexpression of nuclear-localized SIRT3 rescued the senescence phenotypes. Taken together, our study reveals a novel role of nuclear SIRT3 in stabilizing heterochromatin and counteracting hMSC senescence, which may provide new clinical therapeutic targets to ameliorate aging-related diseases.
2021-09-09 | PXD023479 | Pride
Project description:A prevalent view in treating age-dependent disorders including Alzheimer’s disease (AD) is that the underlying amyloid plaque pathology must be targeted for cognitive improvements. In contrast, we report here that repeated scanning ultrasound (SUS) treatment at 1 MHz frequency can ameliorate memory deficits in the APP23 mouse model of AD without reducing amyloid-β (Aβ) burden. Different from previous studies that had shown Aβ clearance as a consequence of blood-brain barrier (BBB) opening, here, the BBB was not opened as no microbubbles were used. Quantitative proteomics and functional magnetic resonance imaging revealed that ultrasound induced long-lasting functional changes that correlate with the improvement in memory. Intriguingly, the treatment was more effective at a higher frequency (1MHz) than at a frequency within the range currently explored in clinical trials in AD patients (286 kHz). Together, our data suggest frequency-dependent bio-effects of ultrasound and a dissociation of cognitive improvement and Aβ clearance, with important implications for the design of trials for AD therapies.
2024-03-19 | PXD050248 | Pride
Project description:The majority of Alzheimer’s disease patients and 20–40% of non-demented elderly experience amyloid deposits along their cerebral vasculature, a condition known as cerebral amyloid angiopathy (CAA). CAA impairs the function of the blood-brain barrier (BBB) leading to ischemia, hemorrhages, and accelerated cognitive dysfunction. The APOE4 allele is the strongest known genetic risk factor for CAA and sporadic AD, however the pathogenic mechanisms underlying this predisposition are unknown. Here, we recreate the human BBB in vitro by co-culturing the three cellular components of the BBB, endothelial cells, pericytes, and astrocytes in 3D scaffolding to construct a tractable model that recapitulates key anatomical and physiological properties of the BBB. Similar to the in vivo BBB, we find amyloid accumulates on our in vitro BBB (iBBB) and both APOE4 homozygous and heterozygous iBBBs exhibit significantly more amyloid accumulation than APOE3/3 iBBBs. Combinatorial experiments revealed that pericytes have a causal role in the development of CAA. We found that APOE expression is markedly up-regulated in APOE4 pericytes, but not in astrocytes or endothelial cells. Transcriptional profiling revealed that calcineurin/NFAT signaling is dysregulated in APOE4 pericytes. Pharmacologically inhibiting calcineurin led to downregulation of APOE and subsequently reduced amyloid deposition on the iBBB. These results demonstrate an unexpected role of pericytes in cerebral amyloid deposition and advocate for inhibiting calcineurin/NFAT-signaling as a therapeutic strategy to mitigate APOE4 predisposition to CAA and potentially AD.
2019-07-31 | GSE125869 | GEO
Project description:Aging is associated with cell senescence and is the major risk factor for AD. We characterized premature cell senescence in post mortem brains from non-diseased controls (NDC) and donors with Alzheimer’s disease (AD) using imaging mass cytometry (IMC) and single nuclear RNA (snRNA) sequencing (>200,000 nuclei). We found increases in numbers of glia immunostaining for galactosidase beta (>4-fold) and p16INK4A (up to 2-fold) with AD relative to NDC. Increased glial expression of genes related to senescence was associated with greater -amyloid load. Prematurely senescent microglia downregulated phagocytic pathways suggesting reduced capacity for -amyloid clearance. Gene set enrichment and pseudo-time trajectories described extensive DNA double-strand breaks (DSBs), mitochondrial dysfunction and ER stress associated with increased β-amyloid leading to premature senescence in microglia. We replicated these observations with independent AD snRNA-seq datasets. Our results describe a burden of senescent glia with AD that is sufficiently high to contribute to disease progression. These findings support the hypothesis that microglia are a primary target for senolytic treatments in AD.
2024-04-26 | GSE264648 | GEO