Modulation of histone H3K4 dimethylation by spermidine ameliorates motor neuron survival and neuropathology in a mouse model of ALS
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PROVIDER: PRJNA879085 | ENA |
REPOSITORIES: ENA
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Project description:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. It has been proposed that epigenetic modification and transcriptional dysregulation may contribute to motor neuron death. In this study, we investigate the basis for therapeutic approaches to target lysine-specific histone demethylase 1 (LSD1) and elucidate the mechanistic role of LSD1-histone H3K4 signaling pathway in ALS pathogenesis. Cellular and animal models of ALS were treated by spermidine (SD), then we performed neuropathological, body weight and survival evaluation in order to examine the role of SD in mutant superoxide dismutase 1 (mSOD1) (G93A) ALS mice. Herein, we found that dimethylated histone H3K4 (H3K4me2) levels are decreased in cellular and animal models of ALS, and correlated with motor neuronal dysfunction in ALS (G93A) mice. SD administration modulated the LSD1 activity and restored H3K4me2 levels in ChAT-positive motor neurons in the lumbar spinal cord of ALS mice. SD prevented cellular damage by improving the number and size of motor neurons in ALS mice. SD administration also reduced GFAP-positive astrogliogenesis in the white and gray matter of the lumbar spinal cord, improving the neuropathology of ALS mice. Moreover, SD administration delayed disease onset and prolonged the lifespan of ALS (G93A) transgenic mice. Together, modulating epigenetic targets such as LSD1 by small compounds may be a useful therapeutic strategy for treating ALS.
2022-09-13 | GSE213091 | GEO
Project description:BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. It has been proposed that epigenetic modification and transcriptional dysregulation may contribute to motor neuron death. In this study, we investigate the basis for therapeutic approaches to target lysine-specific histone demethylase 1 (LSD1) and elucidate the mechanistic role of LSD1-histone H3K4 signaling pathway in ALS pathogenesis.MethodsIn order to examine the role of spermidine (SD), we administered SD to an animal model of ALS (G93A) and performed neuropathological analysis, body weight, and survival evaluation.ResultsHerein, we found that LSD1 activity is increased while levels of H3K4me2, a substrate of LSD1, is decreased in cellular and animal models of ALS. SD administration modulated the LSD1 activity and restored H3K4me2 levels in ChAT-positive motor neurons in the lumbar spinal cord of ALS mice. SD prevented cellular damage by improving the number and size of motor neurons in ALS mice. SD administration also reduced GFAP-positive astrogliogenesis in the white and gray matter of the lumbar spinal cord, improving the neuropathology of ALS mice. Moreover, SD administration improved the rotarod performance and gait analysis of ALS mice. Finally, SD administration delayed disease onset and prolonged the lifespan of ALS (G93A) transgenic mice.ConclusionTogether, modulating epigenetic targets such as LSD1 by small compounds may be a useful therapeutic strategy for treating ALS.
| S-EPMC9764677 | biostudies-literature
Project description:Administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.
2012-01-04 | E-MTAB-912 | biostudies-arrayexpress
Project description:To compare the effects of spermidine, key polyamine, on the gene expression profile of organ cultured human hair follicles Vehicle treated Vs. 0.5 µM spermidine treatment. Two control samples, two spermidine treated samples
2011-04-16 | E-GEOD-28650 | biostudies-arrayexpress
Project description:Spermidine is involved in a variety of biological processes, including DNA metabolism, autophagy and aging. Previous studies have shown that spermidine can increase the percentage of mouse oocytes developing into blastocysts after in vitro fertilization. However, none of the past studies elucidated the effects of spermidine supplementation on porcine oocyte maturation. Here, we choose appropriate dose of spermidine to be added to the maturation medium during in vitro maturation (IVM) to verify whether spermidine can actively promote the maturation of porcine oocytes. Our study provided substantial evidence that spermidine exposure promoted the porcine oocyte meiotic maturation. In addition, single-cell transcriptome analysis identified the target effectors of spermidine actions in porcine oocytes, further demonstrating that spermidine exposure enhanced mitochondrial distribution and function, leading to a reduced excessive oxidative stress-induced DNA damage and early apoptosis of porcine oocytes. These findings demonstrate that spermidine not only delays ageing and cancer treatment, but also improves the quality of germ cells, which may be less likely to suffer from sterility or infertility in humans and animals.
2024-11-30 | GSE217447 | GEO
Project description:We examined the histone modification H3K4 dimethylation (H3K4me2) in the prefrontal cortex of individual Rhesus macaques at different ages by chromatin immunoprecipitation, followed by deep sequencing (ChIP-seq) at the whole genome level
2013-04-01 | GSE41128 | GEO
Project description:To achieve extreme spermidine stress we used DspeG E. coli strain. We identified the pathways that are altered under spermidine stress. Among many changes spermidine altered the iron-sulfur cluster metabolism and redox balance in the cells. Therefore, we have shown that superoxide quencher, NAC and ascorbate mitigates spermidine stress. Overall our data explains the importaance of tight spermidine homeostasisin the cell.
2022-03-01 | GSE186526 | GEO
Project description:To achieve extreme spermidine stress we used DspeG E. coli strain. We identified the pathways that are altered under spermidine stress. Among many changes spermidine altered the iron-sulfur cluster metabolism and redox balance in the cells. Therefore, we have shown that superoxide quencher, NAC and ascorbate mitigates spermidine stress. Overall our data explains the importaance of tight spermidine homeostasisin the cell.
2021-09-01 | GSE154618 | GEO
Project description:We assess the concordance of histone H3 lysine 4 dimethylation (H3K4me2) and trimethylation (H3K4me3) on a genome-wide scale in erythroid development by analyzing pluripotent, multipotential and unipotent cell types. Although H3K4me2 and H3K4me3 are concordant at most genes, multipotential hematopoietic cells have a subset of genes that are differentially methylated (H3K4me2+/me3-). These genes are transcriptionally silent, highly enriched in lineage-specific hematopoietic genes, and uniquely susceptible to differentiation-induced H3K4 demethylation. Self-renewing embryonic stem cells, which restrict H3K4 methylation to genes that contain CpG islands (CGIs), lack H3K4me2+/me3- genes. These data reveal distinct epigenetic regulation of CGI and non-CGI genes during development and indicate an interactive relationship between DNA sequence and differential H3K4 methylation in lineage-specific differentiation. Keywords: comparison of different cell lines Multipotential and erythroid-differentiated hematopoietic cells were compared. Expression was measured using Affymetrix microarrays. H3K4me2 and H3K4me3 enrichment was assessed using Agilent tiling arrays.
2008-04-29 | E-GEOD-11044 | biostudies-arrayexpress
Project description:We examined the histone modification H3K4 dimethylation (H3K4me2) in the prefrontal cortex of individual Rhesus macaques at different ages by chromatin immunoprecipitation, followed by deep sequencing (ChIP-seq) at the whole genome level Four Rhesus macaque prefrontal cortex samples with 0.4, 9,22 and 26 years old were used for H3K4me2 ChIP-Seq
2013-04-01 | E-GEOD-41128 | biostudies-arrayexpress