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miR-197, miR-101, and miR-143 and Pro-Inflammatory Cytokines in Migraine
Roberto Carlos Rosales-Gómez1, Beatriz Teresita Martín-Márquez2,3, Alvaro Jovanny Tovar-Cuevas1
1Centro de Investigación Multidisciplinario en Salud, Departamento de Ciencias Biomédicas, Centro Universitario de Tonalá, Universidad de Guadalajara, Tonalá 45425, Mexico.
Abstract:
Background: Migraine is a disabling neurological disorder where the release of neuropeptides and a local and systemic proinflammatory state prevail. MicroRNAs (miRs) are epigenetic regulators that control the expression of genes involved in inflammation, neovascularization, and pain-related processes. Cytokines mediate the inflammatory state, while miRs can modulate their expression. Methods: This is an analytical and observational study in which subjects with a diagnosis of chronic and episodic migraine and healthy controls were recruited, and the migraine patients were classified by episodic or chronic migraine, as well as with or without aura. Cytokines were measured using the ELISA technique, and the microRNAs hsa-miR-197-3p, hsa-miR-101-3p, and hsa-miR-143-3p were evaluated using qPCR methodology. We also utilized bioinformatic tools, such as miRBase, TargetScan, miRNet, and miRPath, to analyze the interactions and pathways involved. Results: Our findings revealed that hsa-miR-197-3p is elevated in patients without aura (29.91 ± 11.14 with aura vs. 81.10 ± 53.85 without aura, RU; p = 0.021), whereas hsa-miR-143-3p is elevated in episodic migraine (0.0639 ± 0.0227 in EM vs. 0.0308 ± 0.0174, RU p = 0.011). Furthermore, we found higher levels of IL-17 (9.46 ± 1.06 in CM vs. 7.61 ± 2.12 in EM, p = 0.030), IL-6 (4.95 ± 2.84 in CM vs. 1.52 ± 0.98 non-migraine subjects, p = 0.016), and TNFα in chronic migraine patients (0.46 ± 0.24 in CM vs. 0.20 ± 0.05 in non-migraine, p = 0.011 and vs. 0.20 ± 0.13 in EM, p = 0.016). Conclusions: Inflammation is present in migraine regardless of the clinical characteristics of the patients, although it may be accentuated in chronic migraine. Our preliminary findings suggest a potential role for peripheral inflammatory markers, including specific microRNAs (miR-197, miR-101, and miR-143) and cytokines (TNF-α, IL-6, and IL-17A), in the pathophysiology of migraine. These results, although limited by sample size and cross-sectional design, highlight molecular pathways that warrant further investigation.
Insights
Migraine involves inflammation, with specific microRNAs (miRs) and cytokines like IL-17, IL-6, and TNF-α playing potential roles. Elevated miR-197 and miR-143 were observed in certain migraine types, suggesting new diagnostic and therapeutic targets.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Migraine is a disabling neurological disorder characterized by neuropeptide release and inflammation.
- MicroRNAs (miRs) are epigenetic regulators influencing genes involved in inflammation, neovascularization, and pain.
- Cytokines mediate inflammation, and miRs can modulate their expression, suggesting a complex interplay in migraine pathophysiology.
Purpose of the Study:
- To investigate the association between specific microRNAs (hsa-miR-197-3p, hsa-miR-101-3p, hsa-miR-143-3p) and cytokines (IL-17, IL-6, TNF-α) with migraine.
- To differentiate these molecular markers between episodic migraine, chronic migraine, and healthy controls.
- To explore the potential role of these peripheral inflammatory markers in the underlying mechanisms of migraine.
Main Methods:
- Analytical and observational study recruiting patients with episodic and chronic migraine, and healthy controls.
- Cytokine levels measured using ELISA; microRNA expression analyzed via qPCR.
- Bioinformatic tools (miRBase, TargetScan, miRNet, miRPath) used for pathway and interaction analysis.
Main Results:
- hsa-miR-197-3p was elevated in migraine patients without aura (p=0.021).
- hsa-miR-143-3p was elevated in episodic migraine patients (p=0.011).
- Chronic migraine patients exhibited higher levels of IL-17 (p=0.030), IL-6 (p=0.016), and TNF-α (p=0.011) compared to other groups.
Conclusions:
- Inflammation is a common feature in migraine, potentially more pronounced in chronic migraine.
- Specific microRNAs (miR-197, miR-101, miR-143) and cytokines (TNF-α, IL-6, IL-17A) may be implicated in migraine pathophysiology.
- These findings suggest potential peripheral inflammatory markers for further investigation in migraine research, despite limitations in sample size and study design.
