Circular RNA expression profile in the spinal cord of morphine tolerated rats and screen of putative key circRNAs
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE133602 | GEO | 2019/07/02
REPOSITORIES: GEO
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Project description:Morphine tolerance is a tricky problem, the mechanism of it is still unclear. Circular RNAs (CircRNAs) play important roles in biological process of central nervous system. N6-methyladenosine (m6A) as a key post-transcriptional modification of RNA can regulate the metabolism and functions of circRNAs. Here we conducted this research to explore the patterns of m6A-methylation of circRNAs in the spinal cords of 4 morphine tolerated rats and 4 normal rats.
2022-04-05 | GSE199892 | GEO
Project description:Circular RNA expression profile in the spinal cord of morphine tolerated rats and screen of putative key circRNAs
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Project description: Not available
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Project description:The mechanism of morphine tolerance remains unclear, and lncRNA have been promising molecule in many pathophysiological processes. However, the role of lncRNA on morphine tolerance hasn’t been explored yet. So we explore this issue, and our results indicated that the expression profiles of lncRNAs have changed in morphine tolerance rats as compared with normal rats, and among those, some differentially expressed lncRNAs might be new therapeutic targets for morphine tolerance.
2018-04-05 | GSE110115 | GEO
Project description:Epitranscriptomic map of N6-methyladenosine circular RNAs in the spinal cord of morphine-tolerant rats
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Project description:Preclinical studies suggest that parental exposure to drugs of abuse such as opioids can have profound and long-lasting effects on reward processing and drug sensitivity across generations. However, little is known about the impact of long-term paternal morphine exposure on sensitivity to morphine-derived antinociception in offspring. We developed a novel sub-second pain scale with statistical modeling and machine learning to measure mechanical nociception in Long Evans and Sprague Dawley male and female rats. Next, we used this rat pain scale with a multigenerational paternal morphine exposure paradigm to determine whether chronic paternal morphine exposure impacts pain sensitivity in offspring. Finally, we used RNA sequencing to identify potential molecular correlates of sire exposure to morphine on offspring. Surprisingly, we found that von Frey hair filaments (VFHs), the most commonly-used noxious mechanical stimuli to test pain sensitivity, are not painful to rats as measured by this novel rat pain scale. Male progeny produced from morphine-treated sires did not exhibit any baseline changes in sensitivity to noxious mechanical stimuli but had greater sensitivity to the antinociceptive properties of morphine. Changes in gene expression within the periaqueductal gray, including primary members of the RGS family of proteins, were identified that may play a role in modified sensitivity to morphine within offspring. These findings reveal nuanced responses to VFHs that should be considered in future pain studies and demonstrate that long-term paternal exposure to morphine increases sensitivity to morphine-derived analgesia in the subsequent male generation.
2025-05-20 | GSE174846 | GEO
Project description:Morphine and other opioids continue to be commonly utilized as clinical analgesics, despite their numerous adverse side effects, including respiratory depression, addiction, and tolerance. The modulation of µ-opioid receptor (MOR) signaling and subsequent behavioral output is one viable approach to improve opioid therapy. Heat shock protein 90 (Hsp90) is a molecular chaperone protein that has recently been implicated in downstream MOR signaling within the brain in mice. Here we identify a context-dependent impact on MOR signaling in which the inhibition of Hsp90 within the spinal cord promotes morphine induced anti-nociception. We show that intrathecal and not systemic administration of the Hsp90 inhibitors 17-AAG or KU-32 amplifies morphine-induced anti-nociception in both thermal and mechanical pain models. Further, we demonstrate that the inhibition of Hsp90 allows for ERK phosphorylation after opioid treatment. ERK activation was localized within the dorsal horns of the spinal cord, which are heavily populated with primary afferents responsible for nociception. The behavioral effects observed with Hsp90 inhibitors were abolished upon intrathecal U0126 (ERK inhibitor) and cycloheximide (translation inhibitor) treatment, suggesting that downstream ERK phosphorylation and rapid protein translation are responsible for the observed amplification of anti-nociception. Quantitative proteomic analysis identified upregulated RSK with spinal cord Hsp90 inhibition, which we further found was necessary for the observed enhancement of anti-nociception. Taken together, we have uncovered a novel downstream MOR ERK/RSK cascade, localized to the spinal cord and repressed by Hsp90, whose modulation may allow for enhanced efficacy and decreased side effects during opioid therapy.
2020-04-24 | PXD015060 | Pride
Project description:Circular RNA is implicated in numerous diseases and conditions, including traumatic injury to the central nervoussystem. However, we know little regarding their role in completely transected spinal cord injury (SCI). Our studyused high-throughput sequencing to analyze circular RNA expression in rats after experimental completetransection of spinal cord. We found differential expression in 400 circular RNAs after SCI, with 249 significantlyup-regulated and 151 significantly down-regulated. We then selected five circular RNAs for qRT-PCR validation,and the results were in agreement with RNA sequencing. Additionally, we predicted the function of circular RNAin SCI through GO and KEGG analyses, as well as the construction of circRNA/microRNA interaction networks.Furthermore, we identified circular RNA chr9:1829226-1834212 and mRNA Hdac11 as key molecules after SCI.In conclusion, this study is the first to characterize circular RNA function in rats after completely transected SCI,through identifying their differential expression. Our results provide insight into the mechanism and therapeutictargets of SCI.
2020-08-28 | GSE156999 | GEO
Project description:Injured axons in the CNS do not spontaneously regenerate leading to paralysis. Neurons can transport RNA and ribosomes to the site of injury where de novo translation has been known to occur, facilitating repair. Yet the tools available for studying axonal specific RNA are limited. We came up with a simple modification using Cold Active Proteases that enabled us to enrich for axonal RNA from rats with spinal cord injury (SCI) compared to non-injured. Our enriched axonal prep was then analyzed by bulk RNA-seq, where we looked at total RNA and we found differentially expressed genes (DEGs). Analyzing our bulk RNA-seq by Gene Ontology, we found the second most significant pathway for all DEGs was for axonogenesis, with markedly low glial cell contamination. From our DEGs we detected Rims2, which is reported to be predominately a circular RNA (circRNA) in the rodent CNS. Upon further annotation, we found over 200 putative circRNAs. circRNAs are abundant and well conserved in the brain, they are thought to be transcriptional regulators by functioning as microRNA (miR) sponges or binding to RNA-binding proteins (RBPs). By computational analysis using Circular RNA Interactome, we are able to predict which miRs or RBPs could bind to circRims2.
2023-07-25 | GSE230066 | GEO
Project description:BACKGROUND: A growing body of preclinical studies report that parental exposures can impact the behavior and physiology of offspring. Despite the prevalence of opioid exposure throughout human populations, little is known about the impact of paternal (male-line) opioid use on progeny; METHODS: Adult male rats self-administered morphine or saline for 60 days. These sires were then bred to drug-naïve dams to produce first-generation (F1) offspring. Morphine, cocaine, and nicotine self-administration were evaluated in adult F1 progeny. Molecular correlates of addiction-like behaviors in reward-related brain regions were also measured in a cohort of drug-naïve F1 offspring; RESULTS: Male offspring bred from morphine-exposed sires exhibited a dose-dependent increase in morphine self-administration and increased motivation to earn morphine infusions under a progressive ratio schedule of reinforcement. This phenotype was drug-specific, as self-administration of cocaine, nicotine, and sucrose were not altered by paternal morphine history. Accompanying these behavioral changes, increased mu-opioid receptor expression was observed in the ventral tegmental area (VTA), but not the nucleus accumbens (NAc), of male F1 offspring bred from morphine-exposed sires. RNA sequencing further revealed broad transcriptomic alterations to the F1 NAc and VTA transcriptomes; CONCLUSIONS: Paternal morphine exposure increased morphine addiction-like behavioral vulnerability in male progeny. This phenotype may be driven by adaptations to brain regions that modulate reward processing.
2026-05-01 | GSE328531 | GEO