Dataset Information

Combined Transcriptomic and Proteomic Profiling of the Mouse Anterior Cingulate Cortex Identifies Potential Therapeutic Targets for Pulpitis-Induced Pain.

ABSTRACT: Pulpitis is a common dental emergency that presents with intense pain; there is still no specific medicine to treat pulpitis-induced pain to date. Herein, differentially expressed genes in mouse anterior cingulate cortex (ACC) were investigated 7 days after pulp exposure via a combination of high-throughput transcriptomic and proteomic analyses. We screened 34 key genes associated with 8 critical pathways. Among these, genes (Elovl5, Ikbke, and Nbeal2) involved in immune or inflammatory responses exhibited exclusive regulation at the transcriptomic level, as confirmed by qRT-PCR. We also investigated the comprehensive expression profiles of genes (Erg1, Shank2, Bche, Serinf1, and Pax6) related to synaptic plasticity. Furthermore, the underlying mechanisms for pulpitis-induced pain through immune or inflammatory responses and synaptic plasticity were discussed. Taken together, our findings shed light on the mechanisms underlying pulpitis-induced pain, deepening our understanding of the molecular pathways and providing potential therapeutic and diagnostic targets.

SUBMITTER: Kang X

PROVIDER: S-EPMC10851247 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Combined Transcriptomic and Proteomic Profiling of the Mouse Anterior Cingulate Cortex Identifies Potential Therapeutic Targets for Pulpitis-Induced Pain.

Kang Xiaoning X Si Jialin J Zhang Jing J Yan Xia X Yu Zhuo Z Zhang Yaoyuan Y Li Xinwei X Wu Li-An LA

ACS omega 20240125 5

Pulpitis is a common dental emergency that presents with intense pain; there is still no specific medicine to treat pulpitis-induced pain to date. Herein, differentially expressed genes in mouse anterior cingulate cortex (ACC) were investigated 7 days after pulp exposure via a combination of high-throughput transcriptomic and proteomic analyses. We screened 34 key genes associated with 8 critical pathways. Among these, genes (Elovl5, Ikbke, and Nbeal2) involved in immune or inflammatory response ...[more]

PMID: 38343959

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Project description:BackgroundNeuropathic pain (NP) takes a heavy toll on individual life quality, yet gaps in its molecular characterization persist and effective therapy is lacking. This study aimed to provide comprehensive knowledge by combining transcriptomic and proteomic data of molecular correlates of NP in the anterior cingulate cortex (ACC), a cortical hub responsible for affective pain processing.MethodsThe NP model was established by spared nerve injury (SNI) in Sprague-Dawley rats. RNA sequencing and proteomic data from the ACC tissue isolated from sham and SNI rats 2 weeks after surgery were integrated to compare their gene and protein expression profiles. Bioinformatic analyses were performed to figure out the functions and signaling pathways of the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) enriched in.ResultsTranscriptomic analysis identified a total of 788 DEGs (with 49 genes upregulated) after SNI surgery, while proteomic analysis found 222 DEPs (with 89 proteins upregulated). While Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the DEGs suggested that most of the altered genes were involved in synaptic transmission and plasticity, bioinformatics analysis of the DEPs revealed novel critical pathways associated with autophagy, mitophagy, and peroxisome. Notably, we noticed functionally important NP-related changes in the protein that occurred in the absence of corresponding changes at the level of transcription. Venn diagram analysis of the transcriptomic and proteomic data identified 10 overlapping targets, among which only three genes (XK-related protein 4, NIPA-like domain-containing 3, and homeodomain-interacting protein kinase 3) showed concordance in the directions of change and strong correlations between mRNA and protein levels.ConclusionThe present study identified novel pathways in the ACC in addition to confirming previously reported mechanisms for NP etiology, and provided novel mechanistic insights for future research on NP treatment. These findings also imply that mRNA profiling alone fails to provide a complete landscape of molecular pain in the ACC. Therefore, explorations of changes at the level of protein are necessary to understand NP processes that are not transcriptionally modulated.

Project description:Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt-fMRI neurofeedback on pain, we directly compared two different target regions of the pain network, notably the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC). Participants for this prospective study were randomly assigned to two age-matched groups of 14 participants each (7 females per group) for AIC and ACC feedback. First, a functional localizer using block-design heat pain stimulation was performed to define the pain-sensitive target region within the AIC or ACC. Second, subjects were asked to down-regulate the BOLD activation in four neurofeedback runs during identical pain stimulation. Data analysis included task-related and functional connectivity analysis. At the behavioral level, pain ratings significantly decreased during feedback vs. localizer runs, but there was no difference between AIC and ACC groups. Concerning neuroimaging, ACC and AIC showed consistent involvement of the caudate nucleus for subjects that learned down-regulation (17/28) in both task-related and functional connectivity analysis. The functional connectivity toward the caudate nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex. Consequently, the ACC and AIC are suitable targets for real-time fMRI neurofeedback during pain perception as they both affect the caudate nucleus, although functional connectivity indicates that the direct connection seems to be stronger with the ACC. Additionally, the caudate, an important area involved in pain perception and suppression, could be a good rt-fMRI target itself. Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt-fMRI neurofeedback on pain perception.

Dataset Information

Combined Transcriptomic and Proteomic Profiling of the Mouse Anterior Cingulate Cortex Identifies Potential Therapeutic Targets for Pulpitis-Induced Pain.

Publications

Combined Transcriptomic and Proteomic Profiling of the Mouse Anterior Cingulate Cortex Identifies Potential Therapeutic Targets for Pulpitis-Induced Pain.

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