Transcriptional profiling reveals running promotes cerebrovascular remodeling in young but not midlife mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA549482 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We report that running at a young age showed ECM-related changes as well as angiogenesis-related pathways. Midlife running did not show this same affect.
2019-06-19 | GSE132930 | GEO
Project description: Not available
| S-EPMC6854620 | biostudies-literature
Project description:The Apolipoprotein E4 (ApoE4) allele is one of the strongest risk factors for late-onset Alzheimer’s disease (AD) and is associated with a breakdown of the blood-brain barrier and vascular dysfunction (Nation et al 2019; Liu and Bu 2022). Importantly, these vascular pathologies are exacerbated when APOE4 is coexpressed with familial mutations in APP or components of the γ-secretase complex (Montagne and Zlokovic 2021), suggesting that the interactions between APOE4 and AD mutations can drive progression of the disease. However, most studies have been done in aging animals and few look at the impact of APOE4 expression in young animals and how that potentially contributes toward late-stage disease susceptibility. Here, we examined the potential functional interaction between APP mutations and ApoE4 in the progression of AD pathophysiology by comparing the hippocampal transcriptomes of 3-month-old female mice of 4 different genotypes: AppNL-G-F/NL-G-F , which harbours three knock-in mutations in the humanised Aβ region of APP (APP-TKI; Saito et al., 2014), mice with a single allele of human ApoE4 knocked-in, ApoE4+/wt (ApoE4), crosses of these two mouse lines, to create AppNL-G-F/NL-G-F;Apoe4+/wt (double-mutant or DM) mice, and wild-type (WT) mice that served as controls. RNAseq revealed nascent microglial activation signatures in both APP-TKI and double mutant datasets, as well as subtle but significant differences between APP-TKI and double mutant in expression of a subset of vascular remodeling genes.
2024-04-30 | GSE242751 | GEO
Project description:Currently, the mechanisms behind the anti-aging effects of exercise are not understood. The presented study conducted a microarray on hippocampal samples from adult (3.5 month-old) and aged (18 month-old) male BALB/c mice that were individually housed with or without running wheels for 8 weeks. Results showed that aging altered genes related to chromatin remodeling, cell growth, immune activity, and synapse organization compared to adult mice. Exercise was found to modulate many of the genes altered by aging, but in the opposite direction. For example, wheel running increased expression of genes related to cell growth and attenuated expression of genes involved in immune function and chromatin remodeling. Collectively, findings show that even late-onset exercise may attenuate age-related changes in gene expression and identifies possible pathways through which exercise may exert its beneficial effects. In total 20 samples (4 aged exercise, 4 aged sedentary, 6 adult exercise, and 6 adult sedentary) plus 4 technical replicates (24 total) were analyzed.
2012-04-30 | E-GEOD-29075 | biostudies-arrayexpress
Project description:Microglial remodeling of the extracellular matrix promotes synapse plasticity
| PRJNA633361 | ENA
Project description:One pending issue in cardiovascular epigenetics is whether cerebrovascular events, a major complication of atherosclerosis, are associated with any specific DNA methylation changes in the carotid plaque. To clarify that topic, we profiled the DNA methylomes of human symptomatic carotid plaques (SCPs) obtained from patients who suffered cerebrovascular events (n=19) and asymptomatic counterparts (ACP; n=19) with a high-density microarray (~485,000 CpG sites, Illumina), and crossed DNA methylation data with RNAseq-based expression data from an independent SCP set (n=8). Few (30) CpGs showed a significant (p<0.05; absolute Delta-Beta>0.20) differential methylation between the two groups. Within SCPs, methylation correlated significantly with post-cerebrovascular event time (PCET; range: 3-45 days; r-value range -0.926 to 0.857; p<0.05) for ~45,000 CpGs, the vast majority of which became hypomethylated with increasing PCET. Hypomethylation was not due to erasure of the gene-body and CG-poor region hypermethylation that accompany the progression of stable lesions, but rather targeted promoters and CpG islands. Noticeably, promoter hypomethylation and increased expression were observed for genes involved in the inhibition of the inflammatory response, defence against oxidative stress and active DNA demethylation. Our data show that only weak changes in the DNA methylome distinguish symptomatic from asymptomatic carotid plaques, but a widespread demethylation resulting in permissive transcriptional marks at atheroprotective gene promoters is established in plaques after a cerebrovascular event, thus mirroring previous observations that ruptured plaques tend to revert to a more stable structure. The identified loci are candidate targets to accelerate the pace of carotid plaque stabilization. DNA was quantified by Quant-iT PicoGreen dsDNA Reagent (Invitrogen) and the integrity was analyzed in a 1.3% agarose gel. Bisulfite conversion of 600 ng of each sample was perform according to the manufacturer's recommendation for Illumina Infinium Assay. Effective bisulphite conversion was checked for three controls that were converted simultaneously with the samples. 4 ul of bisulfite converted DNA were used to hybridize on Infinium HumanMethylation 450 BeadChip, following Illumina Infinium HD Methylation protocol. Chip analysis was performed using Illumina HiScan SQ fluorescent scanner. The intensities of the images are extracted using GenomeStudio (2011.2) Methylation module (1.8.5) software. Methylation score of each CpG is represented as beta value.
2015-05-14 | E-GEOD-66500 | biostudies-arrayexpress
Project description:Astrocytes, the most prominent glial cell type in the brain, send specialized processes called endfeet around blood vessels and express a large molecular repertoire regulating the cerebrovascular system physiology. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction protein Connexin 43 and 30 (Cx43 and Cx30) allowing in particular for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. In this study, we addressed the specific role of Cx30 at the gliovascular interface. Using an inactivation mouse model for Cx30 (Cx30M-NM-^T/M-NM-^T), we showed that absence of Cx30 does not affect blood-brain barrier (BBB) organization and permeability. However, it results in the cerebrovascular fraction, in a strong upregulation of Sgcg encoding g-Sarcoglycan (SG), a member of the Dystrophin-associated protein complex (DAPC) connecting cytoskeleton and the extracellular matrix. The same molecular event occurs in Cx30T5M/T5M mutated mice, where Cx30 channels are closed, demonstrating that Sgcg regulation relied on Cx30 channel functions. We further characterized the cerebrovascular Sarcoglycan complex (SGC) and showed the presence of M-NM-1-, M-NM-2-, M-NM-4-, M-NM-3-, M-NM-5- and M-NM-6- SG, as well as Sarcospan. Altogether, our results suggest that the Sarcoglycan complex is present in the cerebrovascular system, and that expression of one of its members, g-Sarcoglycan, depends on Cx30 channels. As described in skeletal muscles, the SGC may contribute to membrane stabilization and signal transduction in the cerebrovascular system, which may therefore be regulated by Cx30 channel-mediated functions. Comparison of 3-month-old Cx30 deleted mice against WT genetic background.
2015-03-03 | E-GEOD-59148 | biostudies-arrayexpress
Project description:Currently, the mechanisms behind the anti-aging effects of exercise are not understood. The presented study conducted a microarray on hippocampal samples from adult (3.5 month-old) and aged (18 month-old) male BALB/c mice that were individually housed with or without running wheels for 8 weeks. Results showed that aging altered genes related to chromatin remodeling, cell growth, immune activity, and synapse organization compared to adult mice. Exercise was found to modulate many of the genes altered by aging, but in the opposite direction. For example, wheel running increased expression of genes related to cell growth and attenuated expression of genes involved in immune function and chromatin remodeling. Collectively, findings show that even late-onset exercise may attenuate age-related changes in gene expression and identifies possible pathways through which exercise may exert its beneficial effects.
2012-05-01 | GSE29075 | GEO
Project description:We used RNA sequencing to perform an unbiased interrogation of DG gene expression in CD1 mice exposed to either a voluntary running disc (RUN), a running-independent complex environment (CE, containing a locked disc, social enrichment and tunnels), or a locked disc alone (LD). RNA sequencing revealed that both RUN and CE mice showed significant, and largely non-overlapping, transcriptomic differences versus the LD control. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses about novel mediators of EE-induced cognitive changes.
2018-03-01 | GSE107356 | GEO
Project description:One pending issue in cardiovascular epigenetics is whether cerebrovascular events, a major complication of atherosclerosis, are associated with any specific DNA methylation changes in the carotid plaque. To clarify that topic, we profiled the DNA methylomes of human symptomatic carotid plaques (SCPs) obtained from patients who suffered cerebrovascular events (n=19) and asymptomatic counterparts (ACP; n=19) with a high-density microarray (~485,000 CpG sites, Illumina), and crossed DNA methylation data with RNAseq-based expression data from an independent SCP set (n=8). Few (30) CpGs showed a significant (p<0.05; absolute Delta-Beta>0.20) differential methylation between the two groups. Within SCPs, methylation correlated significantly with post-cerebrovascular event time (PCET; range: 3-45 days; r-value range -0.926 to 0.857; p<0.05) for ~45,000 CpGs, the vast majority of which became hypomethylated with increasing PCET. Hypomethylation was not due to erasure of the gene-body and CG-poor region hypermethylation that accompany the progression of stable lesions, but rather targeted promoters and CpG islands. Noticeably, promoter hypomethylation and increased expression were observed for genes involved in the inhibition of the inflammatory response, defence against oxidative stress and active DNA demethylation. Our data show that only weak changes in the DNA methylome distinguish symptomatic from asymptomatic carotid plaques, but a widespread demethylation resulting in permissive transcriptional marks at atheroprotective gene promoters is established in plaques after a cerebrovascular event, thus mirroring previous observations that ruptured plaques tend to revert to a more stable structure. The identified loci are candidate targets to accelerate the pace of carotid plaque stabilization.
2015-05-14 | GSE66500 | GEO