Abstract Details

Title Exploring the Tripartite Connection Between miRNA, Major Depression and Multiple Sclerosis and Thereby Proposing Their Early Diagnosis and Possible Therapeutic Modalities

Topic Multiple Sclerosis

Presentation(s) P10 - Poster Session 10 (8:00 AM-9:00 AM)

Poster/Presentation
Number 19-005

Objective N/A

Background Major depressive disorder (MDD) and multiple sclerosis (MS) usually find comorbidity and share neuro-immune dysregulation. Mounting evidence suggests that epigenetic mechanisms—mainly comprising miRNAs, DNA-(hydroxy)methylation, and lncRNA-driven chromatin changes—might be a common mechanistic axis. However, there has never been any attempt at integrating the extent to which these phenomena occur, their consistency, as well as their translational relevance across both disorders into one synthesis.

Design/Methods MEDLINE, EMBASE, Scopus, and Web of Science were searched up to 30 April 2024 for studies assessing miRNA expression, DNA/5-hmC marks, histone/chromatin modifications, or lncRNA/ceRNA networks in MDD or MS. Two reviewers independently screened the records, extracted data using a standardised form, and assessed the quality of included studies with the Newcastle–Ottawa Scale (NOS). Due to the heterogeneity in biospecimen and analytical platforms, a narrative synthesis was pursued.

Results 28 primary studies were included. In MDD, the upregulation of miR-221, miR-124-3p, and brain-specific miR-132 was consistently related to impaired Wnt2/CREB/BDNF signalling and limbic network dysfunction. In MS, down-regulation of miR-181a-5p (AUC 0.78), promoter hyper-methylation of MIR21 (relapsing-remitting subtype), and dynamic changes in miR-155 and miR-326 post-disease-modifying therapy were of diagnostic and prognostic value. Cross-disorder convergence entailed the up-regulation of pro-inflammatory miRNAs (miR-155, miR-221), repression of neurotrophic miRNAs (miR-181a, miR-124-3p) and sex-biased silencing of the DLK1-DIO3 imprinted cluster. Functional studies implied the BHMT-betaine methyl cycle, dimethyl-fumarate-mediated chromatin reopening and lncRNAs HOTAIR and MALAT1 as potential upstream regulators.

Conclusions Essentially for deregulated diseases such as MDD and MS, miRNAs, under the supervision of DNA/5-hmC marks and lncRNA-driven chromatin architecture, constitute epigenetic convergence. These stage- and treatment-specific signatures provide an instant promise for biomarkers, whereas mechanistic data identify the upstream targets for the next epigenetic therapies. Therefore, they require prospective multi-omic longitudinal and interventional investigations to determine causality and speed the clinical translation.

Authors/Disclosures
Nimrah Fatima IV, MBBS PRESENTER	Dr. Fatima has nothing to disclose.
Ashvath A. Pillai, Student	Mr. Pillai has nothing to disclose.
Sai Kumar Reddy Pasya, MD, MBBS	Dr. Pasya has nothing to disclose.
Vivek Bokka, MBBS	Dr. Bokka has nothing to disclose.
Japjee Parmar, MBBS	Dr. Parmar has nothing to disclose.
Megha Tiwari, Assistant Professor	Miss Tiwari has nothing to disclose.
Sai Prasad, MBBS	Dr. Prasad has nothing to disclose.
Satya Bora, MBBS	Ms. Bora has nothing to disclose.
Omer Mohammed, MBBS	Mr. Mohammed has nothing to disclose.
Venkateshwaran Vijayanarasimhan	Mr. Vijayanarasimhan has nothing to disclose.
Sambuddha Karmakar	No disclosure on file

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