scholarly journals microRNA-Based Network and Pathway Analysis for Neuropathic Pain in Rodent Models

2022 ◽  
Vol 8 ◽  
Author(s):  
Yi-Li Zheng ◽  
Xuan Su ◽  
Yu-Meng Chen ◽  
Jia-Bao Guo ◽  
Ge Song ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transient Receptor Potential ◽  
Enrichment Analysis ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Functional Enrichment ◽  
Therapeutic Success ◽  
Voltage Gated

Neuropathic pain (NP) is poorly managed, and in-depth mechanisms of gene transcriptome alterations in NP pathogenesis are not yet fully understood. To determine microRNA-related molecular mechanisms of NP and their transcriptional regulation in NP, PubMed, Embase, Web of Science and CINAHL Complete (EBSCO) were searched from inception to April 2021. Commonly dysregulated miRNAs in NP were assessed. The putative targets of these miRNAs were determined using TargetScan, Funrich, Cytoscape and String database. A total of 133 literatures containing miRNA profiles studies and experimentally verify studies were included. Venn analysis, target gene prediction analysis and functional enrichment analysis indicated several miRNAs (miR-200b-3p, miR-96, miR-182, miR-183, miR-30b, miR-155 and miR-145) and their target genes involved in known relevant pathways for NP. Targets on transient receptor potential channels, voltage-gated sodium channels and voltage-gated calcium channels may be harnessed for pain relief. A further delineation of signal processing and modulation in neuronal ensembles is key to achieving therapeutic success in future studies.

Mechanisms and Physiological Implications of Cooperative Gating of Ion Channels Clusters

2021 ◽  
Author(s):  
Rose Ellen Dixon ◽  
Manuel F. Navedo ◽  
Marc D Binder ◽  
L. Fernando Santana
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Transient Receptor Potential ◽  
Imaging Techniques ◽  
Ryanodine Receptors ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Cardiac Cells ◽  
Fine Tuning ◽  
Voltage Gated

Ion channels play a central role in the regulation of nearly every cellular process. Dating back to the classic 1952 Hodgkin-Huxley model of the generation of the action potential, ion channels have always been thought of as independent agents. A myriad of recent experimental findings exploiting advances in electrophysiology, structural biology, and imaging techniques, however, have posed a serious challenge to this long-held axiom as several classes of ion channels appear to open and close in a coordinated, cooperative manner. Ion channel cooperativity ranges from variable-sized oligomeric cooperative gating in voltage-gated, dihydropyridine-sensitive Cav1.2 and Cav1.3 channels to obligatory dimeric assembly and gating of voltage-gated Nav1.5 channels. Potassium channels, transient receptor potential channels, hyperpolarization cyclic nucleotide-activated channels, ryanodine receptors (RyRs), and inositol trisphosphate receptors (IP3Rs) have also been shown to gate cooperatively. The implications of cooperative gating of these ion channels range from fine tuning excitation-contraction coupling in muscle cells to regulating cardiac function and vascular tone, to modulation of action potential and conduction velocity in neurons and cardiac cells, and to control of pace-making activity in the heart. In this review, we discuss the mechanisms leading to cooperative gating of ion channels, their physiological consequences and how alterations in cooperative gating of ion channels may induce a range of clinically significant pathologies.

Calcineurin Regulates Synaptic Plasticity and Nociceptive Transmissionat the Spinal Cord Level

2021 ◽  
pp. 107385842110468
Author(s):  
Yuying Huang ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Protein Phosphatase ◽  
Transient Receptor Potential ◽  
Calcineurin Inhibitors ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Negative Feedback Regulation ◽  
Spinal Cord Level ◽  
Calcineurin Activity

Calcineurin, the predominant Ca2+/calmodulin-dependent serine/threonine protein phosphatase (also known as protein phosphatase 2B), is highly expressed in immune T cells and the nervous system, including the dorsal root ganglion and spinal cord. It controls synaptic transmission and plasticity by maintaining the appropriate phosphorylation status of many ion channels present at presynaptic and postsynaptic sites. As such, normal calcineurin activity in neurons and synapses is mainly involved in negative feedback regulation in response to increased neuronal activity and intracellular Ca2+ levels. Calcineurin inhibitors (e.g., cyclosporine and tacrolimus) are widely used as immunosuppressants in tissue and organ transplantation recipients and for treating autoimmune diseases but can cause severe pain in some patients. Furthermore, diminished calcineurin activity at the spinal cord level may play a major role in the transition from acute to chronic neuropathic pain after nerve injury. Restoring calcineurin activity at the spinal cord level produces long-lasting pain relief in animal models of neuropathic pain. In this article, we provide an overview of recent studies on the critical roles of calcineurin in regulating glutamate NMDA and AMPA receptors, voltage-gated Ca2+ channels, potassium channels, and transient receptor potential channels expressed in the spinal dorsal horn and primary sensory neurons.

scholarly journals Transient Receptor Potential Channels as an Emerging Target for the Treatment of Parkinson’s Disease: An Insight Into Role of Pharmacological Interventions

2020 ◽  
Vol 8 ◽  
Author(s):  
Bhupesh Vaidya ◽  
Shyam Sunder Sharma
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Neurodegenerative Disorder ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Transient Receptor

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the symptoms of motor deficits and cognitive decline. There are a number of therapeutics available for the treatment of PD, but most of them suffer from serious side effects such as bradykinesia, dyskinesia and on-off effect. Therefore, despite the availability of these pharmacological agents, PD patients continue to have an inferior quality of life. This has warranted a need to look for alternate strategies and molecular targets. Recent evidence suggests the Transient Receptor Potential (TRP) channels could be a potential target for the management of motor and non-motor symptoms of PD. Though still in the preclinical stages, agents targeting these channels have shown immense potential in the attenuation of behavioral deficits and signaling pathways. In addition, these channels are known to be involved in the regulation of ionic homeostasis, which is disrupted in PD. Moreover, activation or inhibition of many of the TRP channels by calcium and oxidative stress has also raised the possibility of their paramount involvement in affecting the other molecular mechanisms associated with PD pathology. However, due to the paucity of information available and lack of specificity, none of these agents have gone into clinical trials for PD treatment. Considering their interaction with oxidative stress, apoptosis and excitotoxicity, TRP channels could be considered as a potential future target for the treatment of PD.

scholarly journals Integrative expression network analysis of microRNA and gene isoforms in sacred lotus

2020 ◽  
Author(s):  
Yue Zhang ◽  
Razgar Seyed Rahmani ◽  
Xingyu Yang ◽  
Jinming Chen ◽  
Tao Shi
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Functional Divergence ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Flowering Plant ◽  
Splicing Isoforms ◽  
Gene Isoforms ◽  
Mrna Transcriptome

Abstract Background: Gene expression is complex and regulated by multiple molecular mechanisms, such as miRNA-mediated gene inhibition and alternative-splicing of pre-mRNAs. However, the coordination of interaction between miRNAs with different splicing isoforms, and the change of splicing isoform in response to different cellular environments are largely unexplored in plants. In this study, we analyzed the miRNA and mRNA transcriptome from lotus (Nelumbo nucifera), an economically important flowering plant.Results: Through RNA-seq analyses on miRNAs and their target genes (isoforms) among six lotus tissues, expression of most miRNAs seem to be negatively correlated with their targets and tend to be tissue-specific. Further, our results showed that preferential interactions between miRNAs and hub gene isoforms in one coexpression module which is highly correlated with leaf. Intriguingly, for many genes, their corresponding isoforms were assigned to different co-expressed modules, and they exhibited more divergent mRNA structures including presence and absence of miRNA binding sites, suggesting functional divergence for many isoforms is escalated by both structural and expression divergence. Further detailed functional enrichment analysis of miRNA targets revealed that miRNAs are involved in the regulation of lotus growth and development by regulating plant hormone-related pathway genes.Conclusions: Taken together, our comprehensive analyses of miRNA and mRNA transcriptome elucidate the coordination of interaction between miRNAs and different splicing isoforms, and highlight the functional divergence of many transcript isoforms from the same locus in lotus.

scholarly journals Integrative expression network analysis of microRNA and gene isoforms in sacred lotus

2020 ◽  
Author(s):  
Yue Zhang ◽  
Razgar Seyed Rahmani ◽  
Xingyu Yang ◽  
Jinming Chen ◽  
Tao Shi
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Functional Divergence ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Flowering Plant ◽  
Splicing Isoforms ◽  
Gene Isoforms ◽  
Mrna Transcriptome

Abstract Background Gene expression is complex and regulated by multiple molecular mechanisms, such as miRNA-mediated gene inhibition and alternative-splicing of pre-mRNAs. However, the coordination of interaction between miRNAs with different splicing isoforms, and the change of splicing isoform in response to different cellular environments are largely unexplored in plants. In this study, we analyzed the miRNA and mRNA transcriptome from lotus ( Nelumbo nucifera ), an economically important flowering plant. Results Through RNA-seq analyses on miRNAs and their target genes (isoforms) among six lotus tissues, expression of most miRNAs seem to be negatively correlated with their targets, and tend to be tissue-specific. Further, our results showed that frequent interactions between miRNAs and hub gene isoforms highlight the critical roles of miRNAs in the gene network. Intriguingly, for many genes, their corresponding isoforms were assigned to different co-expressed modules, and they exhibited more divergent mRNA structures including presence and absence of miRNA binding sites, suggesting functional divergence for many isoforms is escalated by both structural and expression divergence. Further detailed functional enrichment analysis of miRNA targets revealed that miRNAs are involved in the regulation of lotus growth and development by regulating plant hormone-related pathway genes. Conclusions Taken together, our comprehensive analyses of miRNA and mRNA transcriptome elucidate the coordination of interaction between miRNAs and different splicing isoforms, and highlight the functional divergence of many transcript isoforms from the same locus in lotus.

Rapid molecular evolution of pain insensitivity in multiple African rodents

Science ◽  
2019 ◽  
Vol 364 (6443) ◽  
pp. 852-859 ◽  
Author(s):  
Ole Eigenbrod ◽  
Karlien Y. Debus ◽  
Jane Reznick ◽  
Nigel C. Bennett ◽  
Oscar Sánchez-Carranza ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Allyl Isothiocyanate ◽  
Transient Receptor Potential Channel ◽  
Leak Channel ◽  
Voltage Gated ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
Transient Receptor

Noxious substances, called algogens, cause pain and are used as defensive weapons by plants and stinging insects. We identified four previously unknown instances of algogen-insensitivity by screening eight African rodent species related to the naked mole-rat with the painful substances capsaicin, acid (hydrogen chloride, pH 3.5), and allyl isothiocyanate (AITC). Using RNA sequencing, we traced the emergence of sequence variants in transduction channels, like transient receptor potential channel TRPA1 and voltage-gated sodium channel Nav1.7, that accompany algogen insensitivity. In addition, the AITC-insensitive highveld mole-rat exhibited overexpression of the leak channel NALCN (sodium leak channel, nonselective), ablating AITC detection by nociceptors. These molecular changes likely rendered highveld mole-rats immune to the stings of the Natal droptail ant. Our study reveals how evolution can be used as a discovery tool to find molecular mechanisms that shut down pain.

Sign in / Sign up

Export Citation Format

Share Document