RNA-Sequencing of carnosine treated wild-type BDF1 (WT) and transgenic Thy1-aSyn mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA475977 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7309690.fastq.gz | Fastqsanger.gz | |||
| SRR7309691.fastq.gz | Fastqsanger.gz | |||
| SRR7309692.fastq.gz | Fastqsanger.gz | |||
| SRR7309693.fastq.gz | Fastqsanger.gz | |||
| SRR7309684.fastq.gz | Fastqsanger.gz |
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Project description:Mitochondrial dysfunction plays a central role in the pathogenesis of neurodegenerative diseases such as Parkinson’s disease (PD). This study tested the hypothesis that the dipeptide carnosine would exert a beneficial effect in the Thy1-aSyn mouse model of PD, which displays mitochondrial dysfunction. Mitochondrial function and gene expression were evaluated in the midbrain after two months of carnosine administration by intranasal (IN) or drinking water routes of exposure. IN carnosine attenuated transcriptional changes in the midbrain in Thy1-aSyn mice. Additionally, IN-carnosine increased expression of mitochondria complexes and enhanced mitochondrial function, suggesting a potential neuroprotective role for IN-carnosine in PD.
2018-12-31 | GSE115769 | GEO
Project description:Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinson’s disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. To gain a better understanding of the consequences of excessive SNCA expression on basal ganglia function, we performed transcriptome analysis of striatal tissue from male Thy1-aSyn-mice and wt littermates. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis.
2012-02-11 | GSE35723 | GEO
Project description:Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinson’s disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. To gain a better understanding of the consequences of excessive SNCA expression on basal ganglia function, we performed transcriptome analysis of striatal tissue from male Thy1-aSyn-mice and wt littermates. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis. The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis. Animal care was conducted in accordance with the U. S. Public Health Service Guide for the Care and Use of Laboratory Animals and procedures were approved by the University of California, Los Angeles (UCLA), I.A.C.U. Committee. Transgenic (tg) mice overexpressing human wt SNCA under the Thy-1 promoter (Thy1-aSyn) created previously in a mixed C57BL/6-DBA background were kept in this background by breeding mutant females with wt males. Only male mice were used in the study. The genotype of all tg and wt mice was verified by PCR analysis of tail DNA. Animals were maintained on a 12 hr light/dark cycle with free access to water and food. Six-month old male Thy1-aSyn and wt littermates were sacrificed by decapitation. For microarray analysis, whole striata from each hemisphere were immediately dissected and pooled for each brain. Tissue was permeated in RNAlater (Qiagen, Valencia, CA), frozen in liquid nitrogen, and stored at - 80º C until used for RNA preparation. For PCR verification of transcriptional changes and for protein extracts preparation, brains from 5 male Thy1-aSyn and 5 wt littermates were obtained as above but then the brains were placed in a metal brain mold with grooves to ensure reproducible cutting of thick brain slices. A first coronal cut was made with a razor blade to remove the frontal part of the brain (at bregma + 1mm, at the anterior level of striatum). The following 1mm coronal slice (including the striatum but no globus pallidus) was used to dissect out striatal tissue. A horizontal cut was made through the anterior commissures to exclude the nucleus accumbens. One cube of striatum was dissected out from each hemisphere, taking care not to include any corpus callosum, choroid plexus, or subventricular zone. Samples were stored at -80º C until further processing. Total RNA was extracted from striata of Thy1-aSyn and wt littermates (all males) with Trizol (Invitrogen, Carlsbad, CA), followed by a clean-up step with RNeasy columns (Qiagen) and RNA integrity check using a Bioanalyzer (Agilent Tech., Foster city, CA). RNA samples were pooled, one pool representing the six control wt mice and the other representing the six SNCA overexpressing animals. After synthesis, using Superscript (Invitrogen) and labeling using the ENZO labeling kit (Affymetrix Inc., Santa Clara, CA), cRNA probes were hybridized to mouse MOE-430A GeneChip arrays (Affymetrix) following the manufacturer’s protocol at the UCLA microarray core facility. Significant differential gene expression between pooled tg and wt samples was ascertained by estimation of signal log2 ratios (or fold changes in expression values), after quality control checks, data normalization and estimating expression values using the Affymetrix Microarray Suite 5.0 Software (MAS 5.0). After pairwise comparisons and filtering of this gene list using the following criteria: change p-value <0.005 for induce genes, change p-value > 0.995 for decreased genes, signal log2 ratio > 0.6 (> 1.52 fold change), excluding probes called absent in both groups, a list of differentially expressed genes was generated. We used various statistical softwares and databases to ascertain pathways affected by overexpression of SNCA that are associated with overrepresented genes in this gene list, including, the functional annotation tools accessible through DAVID (Database for Annotation, Visualization and Integrated Discovery, http://david.abcc.ncifcrf.gov )
2012-02-11 | E-GEOD-35723 | biostudies-arrayexpress
Project description:Mus musculus strain:B6.Cg-Tg(Thy1-YFP)16Jrs/J | breed:Thy1-YFP transgenic mice Raw sequence reads
| PRJNA1158961 | ENA
Project description:To reveal the effects of carnosine on Caco-2 cells, we have employed whole genome microarray to detect genes that showed significantly different expression when exposed to carnosine. Caco-2 cells were treated with 1 mM carnosine for 3 days. Caco-2 cells were treated with 1 mM carnosine for 3 days. Three independent experiments were performed.
2015-03-31 | E-GEOD-61455 | biostudies-arrayexpress
Project description:Bromodomain and Extra-terminal motif (BET) proteins play a central role in transcription regulation and chromatin signalling pathways. In yeast, Bdf1 and its homologous protein Bdf2 are partially redundant and the deletion of both genes is lethal. Most of Bdf1 functions have been investigated in vegetative cells even if this protein is essential for sporulation. In this study, we explored for the first time the functional role of the Bdf1 bromodomains during the sporulation program. Extensive purification of Bdf1 partners identified two independent complexes with Bdf2 or the Swr1 complex. However, none of them are required for meiotic gene regulation or to complete sporulation. Taken together, our results unveil a new role for Bdf1 as a meiotic-specific gene transcriptional regulator independently of its predominant protein partners.
2017-01-11 | PXD005227 | Pride
Project description:To reveal the effects of carnosine on Caco-2 cells, we have employed whole genome microarray to detect genes that showed significantly different expression when exposed to carnosine. Caco-2 cells were treated with 1 mM carnosine for 3 days.
2015-03-31 | GSE61455 | GEO
Project description:Oral consumption of histidyl dipeptides such as l-carnosine has been suggested to promote cardiometabolic health, although therapeutic mechanisms remain incompletely understood. We recently reported that oral consumption of a carnosine analog suppressed markers of fibrosis in liver of obese mice, but whether antifibrotic effects of carnosine extend to the heart is not known, nor are the mechanisms by which carnosine is acting. Here, we investigated whether oral carnosine was able to mitigate the adverse cardiac remodeling associated with diet induced obesity in a mouse model of enhanced lipid peroxidation (i.e., glutathione peroxidase 4 deficient mice, GPx4+/−), a model which mimics many of the pathophysiological aspects of metabolic syndrome and T2 diabetes in humans. Wild-type (WT) and GPx4+/− male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks. Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study. Carnosine treatment led to a moderate improvement in glycemic control in WT and GPx4+/− mice on HFHS diet, although insulin sensitivity was largely unchanged. Interestingly, while our transcriptomic analysis revealed that carnosine therapy had no significant impact on global gene expression in the heart, carnosine substantially upregulated cardiac GPx4 expression in both WT and GPx4+/− mice on HFHS diet. Carnosine also significantly reduced protein carbonyls and iron levels in myocardial tissue from both genotypes on HFHS diet. Importantly, we observed a robust antifibrotic effect of carnosine therapy in hearts from mice on HFHS diet, which further in vitro experiments suggest is due to carnosine’s ability to suppress collagen-cross-linking. Collectively, this study reveals antifibrotic potential of carnosine in the heart with obesity and illustrates key mechanisms by which it may be acting.
2023-12-19 | GSE250315 | GEO
Project description:Alpha-synuclein (aSyn) is a central player in the pathogenesis of synucleinopathies due to its accumulation in typical protein aggregates in the brain. However, it is still unclear how it contributes to neurodegeneration. Type-2 diabetes mellitus is a risk factor for Parkinson’s disease (PD) and, interestingly, a common molecular alteration among these disorders is the age-associated increase in protein glycation. We hypothesized that glycation-induced neuronal dysfunction might be a contributing factor in synucleinopathies. Here, we dissected the specific impact of methylglyoxal (MGO, a glycating agent) in mice overexpressing aSyn in the brain. We found that MGO-glycation potentiates motor, cognitive, olfactory, and colonic dysfunction in aSyn transgenic (Thy1-aSyn) mice that received a single dose of MGO via intracerebroventricular (ICV) injection. aSyn accumulates in the midbrain, striatum, and prefrontal cortex, and protein glycation is increased in the cerebellum and midbrain. SWATH mass spectrometry analysis, used to quantify changes in the brain proteome, revealed that MGO mainly increase glutamatergic-associated proteins in the midbrain (NMDA, AMPA, glutaminase, VGLUT and EAAT1), but not in the prefrontal cortex, where it mainly affects the electron transport chain. Notably, the glycated proteins in the midbrain of Thy1-aSyn mice that received MGO strongly correlate with PD and dopaminergic pathways. Overall, we demonstrated that MGO-induced glycation accelerates PD-like sensorimotor and cognitive alterations and suggest that the increase of glutamatergic signaling may underly these events. Our study sheds new light into the enhanced vulnerability of the midbrain in PD-related synaptic dysfunction and suggests that glycation suppressors and anti-glutamatergic drugs may hold promise as disease-modifying therapies for synucleinopathies.
2022-05-20 | PXD032832 | Pride
Project description:Carnosine is an endogenous β-alanyl-L-histidine dipeptide endowed of antioxidant and carbonyl scavenger properties, able to significantly prevent the visible signs of aging and photoaging. To deeply investigate the mechanism of action of carnosine on human skin proteome, a 3D scaf-fold-free spheroids model of primary dermal fibroblasts from 50-years-old donor, was here adopted in combination with quantitative proteomics
2022-02-22 | PXD031053 | Pride