Activation of S1P2 is protective against cisplatin-induced peripheral neuropathy
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE235877 | GEO | 2024/07/01
REPOSITORIES: GEO
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Project description:Activation of S1P2 is protective against cisplatin-induced peripheral neuropathy
| PRJNA987890 | ENA
Project description:Vincristine, oxaliplatin, and cisplatin are commonly prescribed chemotherapeutic agents for the treatment of several cancer types. However, a main side-effect is chemotherapy-induced peripheral neuropathy (CIPN), which may lead to decreased quality of life, changes in chemotherapeutic treatment or even treatment cessation. Although painful symptoms associated with CIPN are faithfully recapitulated by mouse models, there is limited knowledge of how these drugs affect the expression of genes in peripheral sensory neurons. The present study carried out a transcriptomic analysis of dorsal root ganglia isolated from mice treated with vincristine, oxaliplatin, and cisplatin with a view to gain insight into the comparative pathophysiological mechanisms of CIPN. RNA-Seq using 75-nucleotide single end runs revealed 368, 295 and 256 differential expressed genes (DEGs) induced by treatment with vincristine, oxaliplatin and cisplatin, respectively. Although there were many similarities in DEGs between chemotherapeutic agents, only 5 genes were dysregulated in all groups. Cell type enrichment analysis (CTEA) and gene set enrichment analysis (GSEA) showed predominant effects on genes associated with the immune system after treatment with vincristine, while oxaliplatin treatment affected mainly neuronal genes. Treatment with cisplatin resulted in a mixed inflammatory and neuropathic gene expression signature. Only ‘regulation of transport’ and ‘response to external stimuli’ were gene ontology terms shared between all treatments. These results provide insight into the recruitment of innate and adaptive immune responses to DRG tissue and indicate enhanced neuro-inflammatory processes following administration of vincristine, oxaliplatin, and cisplatin. These gene expression signatures may provide insight into novel drug targets for treatment of CIPN.
2019-06-01 | GSE125002 | GEO
Project description:To compare the microRNAs (miRNAs) expression profile in the innervated soleus muscle and L4-L6 DRG neuronsafter sciatic nerve entrapment with a non-constrictive silastic tube, subsequent surgical decompression, and denervation injury. The experimental soleus muscles and dorsal root ganglions (DRGs) from each experimental group (sham control, denervation, entrapment, and decompression) were analyzed with an Agilent® rat miRNA array to detect dysregulated miRNAs Three-condition experiment, DRGs and soleus muscles of the rats receiving sciatic nerve denervation 6 months, sciatic nerve entrapment 6 months, and sciatic nerve entrapment 6 months then decompression for 3 months v.s. soleus muscle (sham control), Biological replicates: 1 control replicates, 3 experiment replicates
2010-06-12 | E-GEOD-22181 | biostudies-arrayexpress
Project description:Chemotherapy induced peripheral neuropathy (CIPN) is a dose-limiting painful neuropathy that occurs commonly during cancer management, which often leads to the discontinuation of medication. Previous studies suggest that the α9α10 nicotinic acetylcholine receptor (nAChR) specific antagonist αO-conotoxin GeXIVA[1,2] is effective in CIPN models, however the related mechanisms remains unclear. Here we analyzed the preventive effect of GeXIVA[1,2] on neuropathic pain in the long-term oxaliplatin injection induced CIPN model. At the end of treatment, lumbar (L4-L6) spinal cord was extracted, and RNA-sequencing and bioinformatic analysis were performed to investigate the potential genes and pathways related to CIPN and GeXIVA[1,2]. GeXIVA[1,2] inhibited the development of mechanical allodynia induced by chronic oxaliplatin treatment. Repeated injections of GeXIVA[1,2] for 3 weeks have no effect on mice normal pain threshold or locomotor activity and anxiety-like behavior as evaluated in the open field test (OFT) and elevated plus maze (EPM). Our RNA-sequencing results identified 209 differentially expressed genes (DEGs) in CIPN model, simultaneously injection of GeXIVA[1,2] with oxaliplatin altered 53 of the identified DEGs. These reverted genes were significantly enriched in immune-related pathways represented by cytokine-cytokine receptor interaction pathway. Our findings suggest that GeXIVA[1,2] could be a potential therapeutic compound for chronic oxaliplatin induced CIPN management.
2024-01-18 | GSE253183 | GEO
Project description:To compare the microRNAs (miRNAs) expression profile in the innervated soleus muscle and L4-L6 DRG neuronsafter sciatic nerve entrapment with a non-constrictive silastic tube, subsequent surgical decompression, and denervation injury. The experimental soleus muscles and dorsal root ganglions (DRGs) from each experimental group (sham control, denervation, entrapment, and decompression) were analyzed with an Agilent® rat miRNA array to detect dysregulated miRNAs
2010-06-12 | GSE22181 | GEO
Project description:Vincristine, oxaliplatin, and cisplatin are commonly prescribed chemotherapeutic agents for the treatment of several cancer types. However, a main side-effect is chemotherapy-induced peripheral neuropathy (CIPN), which may lead to decreased quality of life, changes in chemotherapeutic treatment or even treatment cessation. Although painful symptoms associated with CIPN are faithfully recapitulated by mouse models, there is limited knowledge of how these drugs affect the expression of genes in peripheral sensory neurons. The present study carried out a transcriptomic analysis of dorsal root ganglia isolated from mice treated with vincristine, oxaliplatin, and cisplatin with a view to gain insight into the comparative pathophysiological mechanisms of CIPN. RNA-Seq using 75-nucleotide single end runs revealed 368, 295 and 256 differential expressed genes (DEGs) induced by treatment with vincristine, oxaliplatin and cisplatin, respectively. Although there were many similarities in DEGs between chemotherapeutic agents, only 5 genes were dysregulated in all groups. Cell type enrichment analysis (CTEA) and gene set enrichment analysis (GSEA) showed predominant effects on genes associated with the immune system after treatment with vincristine, while oxaliplatin treatment affected mainly neuronal genes. Treatment with cisplatin resulted in a mixed inflammatory and neuropathic gene expression signature. Only ‘regulation of transport’ and ‘response to external stimuli’ were gene ontology terms shared between all treatments. These results provide insight into the recruitment of innate and adaptive immune responses to DRG tissue and indicate enhanced neuro-inflammatory processes following administration of vincristine, oxaliplatin, and cisplatin. These gene expression signatures may provide insight into novel drug targets for treatment of CIPN.
2019-06-01 | GSE125001 | GEO
Project description:Neuropathic pain, a consequence of somatosensory nervous system injury or disease, is commonly associated with cancer and its treatments, including chemotherapy-induced peripheral neuropathy (CIPN). However, the mechanisms underlying CIPN-induced proteome aggregation remain elusive due to limited detection tools. Here, we present a combined approach employing fluorescence imaging and proteomic sensors to comprehensively study proteome aggregation in neuronal cells subjected to CIPN. The AggStain imaging probe sensitively detected proteome aggregation, while the AggLink proteomic sensor captured and profiled aggregated proteins. This integrative sensor system offers novel insights into proteome aggregation dynamics in CIPN and highlights its potential for broader applications in assessing proteome stability under various conditions.
2023-10-09 | PXD045972 |
Project description:G protein-coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR, and its function remains largely unknown. Here we report that Gpr37l1 and GPR37L1 are among the most highly expressed GPCR transcripts in mouse and human dorsal root ganglia (DRGs) and are selectively expressed in satellite glial cells (SGCs). Peripheral neuropathy following PTX-induced pain resulted in a downregulation of GPR37L1 plasma membrane expression in DRGs. Transgenic mice with Gpr37l1 deficiency exhibited impaired resolution of neuropathic pain symptoms following PTX-induced pain, whereas overexpression of Gpr37l1 in mouse DRGs reversed pain. GPR37L1 regulates the surface expression and function of these potassium channels. Thus, GPR37L1 in SGCs offers a new target for neuropathy protection and pain control.
2024-03-06 | GSE260669 | GEO
Project description:Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of cancer treatment, often leading to cessation of therapy due to lack of adequate treatment options. In the peripheral nervous system the chemotherapeutic agent paclitaxel impairs mitochondrial function and induces vast changes in gene expression. However, changes at the protein level remain so far unexplored. Here we used an unbiased approach of quantitative proteome profiling in a clinically-relevant rat model of paclitaxel-induced peripheral neuropathy. We analysed two critical timepoints: (1) day 7, equivalent to 1 day after cessation of paclitaxel treatment, prior to neuropathy development; (2) approximately 4 weeks after paclitaxel initiation, when neuropathy has developed.
2022-03-24 | PXD028356 | Pride
Project description:We randomly selected 60 patients who completed paclitaxel treatment for high-throughput sequencing. Grade 2 or higher (grade 2+) neuropathy has been defined as high-PIPN and Grade 1 as low-PIPN according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE version 4.0) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). We compared gut microbiome signatures in high-PIPN, low-PIPN, and healthy controls.
2023-10-12 | E-MTAB-13423 | biostudies-arrayexpress