Transcriptomic landscape of the Dorsal Root Ganglia (DRG) and the Sciatic Nerve (SN) in a mouse model of Paclitaxel-Induced Peripheral Neuropathy (PIPN)
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PROVIDER: PRJNA1049871 | ENA |
REPOSITORIES: ENA
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Project description:Extensive transcriptomic changes associated with paclitaxel-induced peripheral neuropathy in mice: Differential effects in dorsal root ganglia and the sciatic nerve Background: Paclitaxel (Ptx)-induced peripheral neuropathy (PIPN), a common side effect of this anti-cancer drug, causes chronic pain reflecting the molecular changes in the dorsal root ganglion (DRG) of the sciatic nerve (SN). While the subcellular localization and spatio-temporal control of mRNA translation are critical to nerve function, little is known about the transcriptional landscapes of DRG and SN in PIPN. Aim: Transcriptome-wide assessment of Ptx-induced changes in gene expression and mRNA distribution in DRG or SN. Methods: Gene expression microarray analysis of the subcellular transcriptomes of DRG and SN in normal and PIPN mice with Transcriptome Analysis Console followed by analysis with 11 pathway databases. Validation of selected results in cultured cells and animal tissues. Results: In normal mice, transcripts were differentially distributed in DRG and SN. In PIPN, both the gene expression profile and the distribution of the transcripts between DRG and SN were changed compared to normal controls. Functional analysis of gene clusters confirmed changes in pathways known to be affected by Ptx including including cytoskeleton remodeling, cell cycle regulation, immune response and neuronal transmission, as well as less studied pathways such as fatty acid metabolism, Rho GTPases in Wnt signaling, G-protein signal transduction, mRNA splicing and editing. Although the expression and function of cytoskeleton genes is known to be disturbed by Ptx, we found actins, actinins and non-muscle myosins (actomyosin contractility cluster) to be overexpressed by Ptx and accumulated specifically in the SN. For instance, in PIPN, the normalized ratio of SN/DRG mRNA levels for Myh7, Myh2, Actn2, Acta2 and Actb was 32.4, 24.5, 21.9, 3.6 and 3.3 respectively. We also identified transcripts overexpressed and accumulated in PIPN DRGs, with the highest DRG/SN mRNA ratios found for ion channels (ratios in parentheses) SN10a, Kcnd1, Atp1a3, Kcnip3, SN11a, (10.3-21.2); neurotransmitter regulators Syt1, Gabbr2 (14.4, 13.2); fatty acid regulators: Fabp4, Adipoq (22.9, 4.8), some tubulins: Tubb3, Tubb4a, Tubb4b (9.15, 5.5, 2.0) as well as GPCR regulating proteins: Rasgrp1, Gnal, Olfr1098 (16.7, 7.6, 2.0). Furthermore, the Wikipathways integrated with the Transcriptome Analysis Console revealed that GPCRs were the most significantly altered class of genes, predominantly downregulated by Ptx compared to Naive samples in the DRG (320 downregulated, 88 upregulated) and in the SN (469 downregulated, 74 upregulated). In contrast, the comparison of control Naive samples in the DRG versus SN showed minimal changes (21 downregulated, 5 upregulated). These changes were statistically significant with a p-value < 0.001 and a fold change of -2 > FC > 2. Conclusion: Our results show that Ptx not only affects the gene expression but also the subcellular localization of transcripts kept in DRG bodies or over-transported to distal parts of Sciatic Nerve along the longest axon of the body. Cargo trafficking including RNA shuttles among nucleus- cytoplasm-axon terminal of nerves might be one of the most critical processes impaired in PIPN. These results might be used in the future to develop a potential therapeutic strategy focusing on normalization of axon cargo trafficking and PIPN prevention.
2023-12-08 | GSE249643 | GEO
Project description:Female mouse models of diabetic peripheral neuropathy (DPN) have not yet been identified. Our aim is firstly to demonstrate that female BTBR ob/ob mice display robust DPN and secondly, to perform relevant comparisons with non-diabetic and gender-matched controls. Lastly, microarray technology was employed to identify dysregulated genes and pathways in the SCN and DRG of female BTBR mice. Dorsal root ganglia (DRG) and sciatic nerve (SCN) were removed from female mice, RNA isolated and processed for gene expression profiling to identify differentially expressed genes using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays.
2016-07-12 | GSE70852 | GEO
Project description:Purpose: compare the gene expression in whole sciatic DRG of aged mice preceding and after sciatic nerve injury (SNI) compared to the young Results: we found ageing-dependent gene expression changes repressing axonal regeneration following sciatic nerve injury
2022-01-01 | GSE149770 | GEO
Project description:Analysis of gene expression in injured primary DRG with or without camptothecin (CPT) treatment after sciatic nerve crushing may help us identify critical molecular pathways related to axon regeneration. We performed RNA-sequencing of (i) Naive primary DRG tissues without injury, (ii) Primary DRG tissues with vehicle treatment different time-points (18, 24, 36 hours) after sciatic nerve injury, and (iii) Primary DRG tissues with camptothecin treatment different time-points (18, 24, 36 hours) after sciatic nerve injury.
2020-07-24 | GSE113672 | GEO
Project description:Paclitaxel-induced peripheral neuropathy is a significant problem, which afflicts up to 70% of chemotherapy patients. Therapeutic interventions are currently unavailable due to an incomplete understanding of the underlying mechanisms. We previously discovered a major target in the skin, MMP-13, which underlies the development of paclitaxel-induced peripheral neuropathy in zebrafish and rodents. To better understand gene expression changes in sensory neurons and target tissue prior to and during the progression of neuropathy, we performed longitudinal RNA sequencing of mouse skin and dorsal root ganglion (DRG) neurons. Samples were harvested at time points associated with behavioural responses following injection of mice for 7 days either with vehicle or paclitaxel. The responses were categorized into pain onset (day 4 of paclitaxel injection), maxima (d7), beginning of pain resolution (d11) and recovery phase (d23). This dataset will be useful to understand changes in gene regulation in both neurons and skin, which can aid in the discovery of therapeutic interventions.
2021-10-12 | GSE185084 | GEO
Project description:Expression of L4 DRG after sciatic nerve cut compared to contralateral uninjured DRGs. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0003322 Keywords: Expression profiling by array
2017-04-26 | GSE96051 | GEO
Project description:Diabetic peripheral neuropathy (DPN) is the most common form of neuropathy, and have considerable morbidity, which occurs in approximately 50% of diabetic patients. Here, we performed scRNA-seq technology using 10× Genomics sequencing on DRG tissues isolated from control and DPN rats, to identify the cell type composition of DRG, and to reveal the roles of different cell types in mediating DPN.
2023-11-23 | GSE248328 | GEO
Project description:RNA sequencing of whole sciatic Dorsal Root Ganglia (DRG) from young and aged mice
| PRJNA630078 | ENA
Project description:Nerve injury in the peripheral nervous system allows spontaneous regeneration, in contrast to injury of central nerves, which lead to a differential expression pattern of regeneration-associated genes and others. These genes might be regulated by promoter DNA methylation As regeneration model, DRG tissue was analyzed for methyated gene promoters and CpG islands following both injury types. A differential methylation pattern could be identified, although most genes remained unmethylated. comparison of DRG following either sciatic nerve axotomy (SNA) or dorsal column axotomy (DCA) - each 'real injury or sham' - at 1, 3 or 7 days post-injury vs. 'naive', Each sample was pooled from two mice, yielding an immunoprecipitated sample ('Test') and an input genomic DNA sample (Ref). altogether 33 microarrays were used for 13 conditions with triplicate arrays for 'real injury' or 'naive' samples, and duplicate arrays for 'sham' samples.
2014-03-05 | E-GEOD-55514 | biostudies-arrayexpress
Project description:We used microarrays to distinguish the gene expression differences among different time points after injury. We generated L4-6 dorsal root ganglia (DRG) tissues and proximal sciatic nerve (SN) tissues (0.5cm) at 0d, 1d, 4d, 7d and 14d after sciatic nerve resection.
2013-01-01 | E-GEOD-30165 | biostudies-arrayexpress