In situ tissue profile of rat trigeminal nerve in trigeminal neuralgia using spatial transcriptome sequencing
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ABSTRACT: Investigation on the transcriptome and intercellular communication of different cells of trigeminal nerve in trigeminal neuralgia rat by spatial transcriptome sequencing
Project description:Trigeminal neuralgia (TN) is a type of neuropathic pain caused by injury to sensory nerves, manifesting as severe paroxysmal pain of the head and face. Trigeminal neuralgia brings a huge burden to patients, without long-term effective treatment. Changes in the expression of pain-related genes in the whole blood samples of patients play an important role in the pathogenesis, diagnosis, and evaluation of treatment effects of trigeminal neuralgia. To better understand the mechanism of trigeminal neuralgia, we collect the whole blood samples from the trigeminal neuralgia patients and the pain-free healthy comparisons. RNA-seq was conducted between the two groups to find the transcriptome changes in patients with trigeminal neuralgia.
Project description:The epigenetic roles in trigeminal neuralgia (TN) still remain unclear. H3K9ac alteration in neuralgia is obscure and controversy. In this study, we established TN rat model via chronic compression, and further treated with 100 mg/kg/d carbamazepine (CBZ). RNA-seq were conducted to investigate the transcriptional profilings in control, TN and TN+CBZ.
Project description:The epigenetic roles in trigeminal neuralgia (TN) still remain unclear. H3K9ac alteration in neuralgia is obscure and controversy. In this study, we established TN rat model via chronic compression, and further treated with 100 mg/kg/d carbamazepine (CBZ). ChIP-seq were conducted to investigate the genome-wide distribution of H3K9ac and HDAC3 in control, TN and TN+CBZ.
Project description:The cerebral cortex plays a key role in the multi-dimensional human pain experience. However, the neural mechanisms mediating pain-related cortical activity remain largely unknown, particularly in primary somatosensory cortex (S1). We therefore developed a new animal model of trigeminal neuralgia, a prototypical neuropathic pain, which allowed us to evaluate pain-related cortical dynamics with unprecedented translational relevance. Our novel model (FLIT: Foramen Lacerum Impingement of Trigeminal-nerve) displayed robust clinically relevant trigeminal neuralgia-like behaviors, including asymmetric facial grimacing, dental pain-like behaviors, anxiety-like behavior, and sexual dysfunction, capturing many features of the human pain experience. Awake FLIT mice exhibited highly synchronized spontaneous population activity in S1, due to GABAergic interneuron hypoactivity. Remarkably, clinically effective treatments including carbamazepine and trigeminal nerve root decompression abrogated S1 synchronization and alleviated trigeminal neuralgia-like behaviors. These results reveal synchronized S1 activity as a new and important cortical substrate of neuropathic pain, which can be clinically targeted to provide effective therapy.
Project description:BackgroundTrigeminal neuralgia (TN) is the most common neuropathic disorder in the maxillofacial region. The etiology and pathogenesis of TN have not been clearly determined to date, although there are many hypotheses.ObjectiveThe goal of this study was to investigate the interactions between different types of cells in TN, particularly the impact and intrinsic mechanism of demyelination on the trigeminal ganglion, and to identify new important target genes and regulatory pathways in TN.MethodsTN rat models were prepared by trigeminal root compression, and trigeminal nerve tissues were isolated for spatial transcriptome sequencing. The gene expression matrix was reduced dimensionally by PCA and presented by UMAP. Gene function annotation was analyzed by Metascape. The progression of certain clusters and the developmental pseudotime were analyzed using the Monocle package. Modules of the gene coexpression network between different groups were analyzed based on weighted gene coexpression network analysis and assigned AddModuleScore values. The intercellular communication of genes in these networks via ligand-receptor interactions was analyzed using CellPhoneDB analysis.ResultsThe results suggested that the trigeminal ganglion could affect Schwann cell demyelination and remyelination responses through many ligand-receptor interactions, while the effect of Schwann cells on the trigeminal ganglion was much weaker. Additionally, ferroptosis may be involved in the demyelination of Schwann cells.ConclusionsThis study provides spatial transcriptomics sequencing data on TN, reveals new markers, and redefines the relationship between the ganglion and myelin sheath, providing a theoretical basis and supporting data for future mechanistic research and drug development.
Project description:Nogo-A is a major regulator of neural development and regeneration in the central nervous system, but its role in tooth innervation remains largely unknown. Neurons of the trigeminal ganglion innervate the teeth. We showed that Nogo-A is expressed in the trigeminal ganglion and tooth-related nerve fibres. Nogo-A deletion in mice leads to a less complex neuronal network when compared to wild-type animals. Bulk RNA sequencing on the trigeminal ganglia of Nogo-A KO and wild-type mice revealed gene expression changes associated with alterations in neurotrophin signalling and neuronal synaptic formation during the development and maturation of the trigeminal neurons.
Project description:The trigeminal ganglion is a critical structure in the peripheral nervous system, responsible for transmitting sensations of touch, pain, and temperature from craniofacial regions to the brain. Trigeminal ganglion development depends upon intrinsic cellular programming as well as extrinsic signals exchanged by diverse cell populations. With its complex anatomy and dual cellular origin from cranial placodes and neural crest cells, the trigeminal ganglion offers a rich context for examining diverse biological processes, including cell migration, fate determination, adhesion, and axon guidance. Avian models have, so far, enabled key insights into craniofacial and peripheral nervous system development. Yet, the molecular mechanisms driving trigeminal ganglion formation and subsequent nerve growth remain elusive. In this study, we performed RNA-sequencing at multiple stages of chick trigeminal ganglion development and generated a novel transcriptomic dataset that has been curated to illustrate temporally dynamic gene expression patterns. This publicly available resource identifies major pathways involved in trigeminal gangliogenesis, particularly with respect to the condensation and maturation of placode-derived neurons, thus inviting new lines of research into the essential processes governing trigeminal ganglion development.