Regulation of brain aging by neutral sphingomyelinase 2
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ABSTRACT:
PROVIDER: PRJNA742012 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: The goals of this study are to compare next generation sequencing-derived brain cortex transcriptome profiling (RNA-seq) to study the role of neutral sphingomyelinase 2 (smpd3) in brain aging. Methods: Brain cortex mRNA profiles of 10 month old (fro/+) and smpd3 total knockout (fro/fro) mice were generated by deep sequencing, in duplicate, using Illumina NovaSeq 6000. (https://en.novogene.com) Results:A total of 1462 transcripts differed between genotypes, with 891 transcripts increased and 571 transcripts decreased. Conclusions: Transcriptome differences link decreased oxidative stress and astrocyte activation in brain cortex to nSMase2 deficiency, while synaptic signaling transcripts increased in ways consistent with increased cognitive function previously demonstrated in nSMase2-deficient mice.
2022-04-27 | GSE179045 | GEO
Project description:The aging brain is highly vulnerable to cellular stress, and neurons often employ numerous mechanisms to combat neurotoxic proteins and promote healthy brain aging. The RNA modification m6A has been shown to be a critical regulator of RNA stability and translation in cells during stress. m6A is highly enriched in the Drosophila brain and is critical for the acute heat stress response. Here we examine m6A response to chronic stresses of aging and degenerative disease. In the brain, m6A levels dynamically increased with age and disease, marking critical signaling pathway transcripts that become downregulated in age and disease. Unexpectedly, there is opposing regulation of m6A transcript translation in neural vs glial cells, which conferred different outcomes on animal healthspan with Mettl3 knockdown to reduce m6A. Moreover, these data reveal that knockdown of Mettl3 in glial tauopathy is beneficial, leading to increased animal survival. These findings provide mechanistic insight into regulation of m6A modified transcripts with age and disease that varies based on cell type.
2023-12-28 | GSE235989 | GEO
Project description:MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 233 known miRNAs and identification of 41 novel miRNAs. Of these miRNAs, 75 known and 18 novel miRNAs exhibit greater than 2.0-fold expression changes. The majority of expressed miRNAs in our study decline in relative abundance in the aged brain, in agreement with trends observed in other miRNA studies in aging tissues and organisms. Target prediction analysis suggests that many of our novel aging-associated miRNAs target genes in the insulin signaling pathway, a central node of aging-associated genetic networks. These novel miRNAs may thereby regulate aging-related functions in the brain. Since mouse miRNAs are conserved in humans, the aging-affected brain miRNAs we report here may represent novel regulatory genes that function during aging in the human brain. 2 samples examined: Mouse brain from two young (5 months) and two old animals (24-25 months).
2012-05-31 | E-GEOD-34393 | biostudies-arrayexpress
Project description:Genetics of Mood Disorders: Aging and Emotion Regulation Brain Circuitry in Bipolar
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Project description:Genetics of Mood Disorders: Aging and Emotion Regulation Brain Circuitry in Bipolar
| PRJNA476663 | ENA
Project description:MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 233 known miRNAs and identification of 41 novel miRNAs. Of these miRNAs, 75 known and 18 novel miRNAs exhibit greater than 2.0-fold expression changes. The majority of expressed miRNAs in our study decline in relative abundance in the aged brain, in agreement with trends observed in other miRNA studies in aging tissues and organisms. Target prediction analysis suggests that many of our novel aging-associated miRNAs target genes in the insulin signaling pathway, a central node of aging-associated genetic networks. These novel miRNAs may thereby regulate aging-related functions in the brain. Since mouse miRNAs are conserved in humans, the aging-affected brain miRNAs we report here may represent novel regulatory genes that function during aging in the human brain.
2012-06-01 | GSE34393 | GEO
Project description:DNA methylation plays crucial roles during fetal development as well as aging. Whether the aging of the brain is programmed at the fetal stage remains untested. To test this hypothesis, mouse epigenetic clock (epiclock) was profiled in fetal (gestation day 15), postnatal (day 5), and aging (week 70) brain of male and female C57BL/6J inbred mice. Data analysis showed that on week 70, the female brain was epigenetically younger than the male brain. Predictive modeling by neural network identified specific methylations in the brain at the developing stages that were predictive of epigenetic state of the brain during aging. Transcriptomic analysis showed coordinated changes in the expression of epiclock genes in the fetal brain relative to the placenta. Whole-genome bisulfite sequencing identified sites that were methylated both in the placenta and fetal brain in a sex-specific manner. Epiclock genes and genes associated with specific signaling pathways, primarily the gonadotropin-releasing hormone receptor (GnRHR) pathway, were associated with the sex-bias methylations in the placenta as well as the fetal brain. Transcriptional crosstalk among the epiclock and GnRHR pathway genes was evident in the placenta that was maintained in the brain during development as well as aging. Collectively, these findings suggest that sex differences in the aging of the brain are of fetal origin and epigenetically linked to the placenta.
2022-08-22 | GSE157553 | GEO
Project description:Analysis of proteome changes during mouse brain aging
| MSV000082968 | MassIVE
Project description:SMPD4 (neutral sphingomyelinase-3/nSMase3) has recently been shown to be a new cause of microcephaly in a cohort of twenty-three pediatric patients. The function of nSMases in brain development and how SMPD4 variants cause human microcephaly and cerebellar hypoplasia was previously unknown.We developed an iPSC model to complement our mouse study. We found iPSC models from human SMPD4 patient and CRISPR/Cas9-induced SMPD4 knockout lines demonstrate a proliferation defect, increased cell death, loss of neural progenitors, and shortened primary cilia. Treatment with exogenous ceramide significantly rescues the cilia defect. SMPD4 patient and knockout cells have altered WNT signaling. We provide evidence that SMPD4 controls brain development by providing ceramide for primary ciliogenesis, suggesting a novel therapeutic strategy for SMPD4 mediated disease.
2023-12-24 | GSE250472 | GEO
Project description:Transcriptome profiling of the aging fly brain
| PRJNA418957 | ENA