Circular RNA signatures in vestibular migraine and migraine from cold regions: Preliminary mechanistic insights

Abstract

Background Vestibular migraine (VM) is a common disorder characterized by recurrent dizziness or vertigo, often aggravated by cold exposure. This study aimed to identify differentially expressed circular RNAs (circRNAs) in cold-region VM and explore the underlying molecular mechanisms. Methods Peripheral blood samples from long-term residents of Heilongjiang Province profiled by circRNA microarray, and differentially expressed circRNAs were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A competing endogenous RNA (ceRNA) network and enriched pathways were inferred by bioinformatics. A VM-like mouse model was established using nitroglycerin (NTG) and kainic acid (KA) and confirmed by behavioral testing and western blot. The hsa_circ_0003201/miR-31-5p/triggering receptor expressed on myeloid cells 2 (TREM2) axis and related pathways were examined in clinical samples and in the trigeminal nucleus caudalis (TNC) and vestibular nuclei (VN) of mice using qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and western blot. CircRNA microarray profiling also compared expression patterns between VM and migraine patients. Results Hsa_circ_0003201 was significantly upregulated in cold-region VM patients. Bioinformatic analyses revealed that hsa_circ_0003201 may regulate the miR-31-5p/TREM2 axis and be associated with phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling, pyruvate metabolism, and transient receptor potential (TRP) pathways. Clinical validation confirmed increased hsa_circ_0003201 and TREM2 and decreased miR-31-5p. VM-like mice exhibited central sensitization and vestibular dysfunction, with increased TREM2, decreased miR-31-5p, and PI3K/AKT activation in the TNC and VN. Comparative circRNA analysis between VM and migraine patients indicated distinct expression patterns. Conclusion Hsa_circ_0003201 shows potential as a diagnostic biomarker for cold-region VM, and the hsa_circ_0003201/miR-31-5p/TREM2 axis may contribute to pathogenesis through PI3K/AKT signaling, pyruvate metabolism, and TRP-related pathways.

Keywords

circRNA / vestibular migraine / cold regions

Acknowledgements

Not applicable.

Research ethics

This study received approval from the Ethics Committee of the First Affiliated Hospital of Harbin Medical University (IRB-AF/ SC-12/03.0), and written informed consent was obtained from all participants. All animal experiments were conducted in accor-dance with protocols approved by the Institutional Animal Care and Use Committee of the same institution (2022-K98).

Informed consent

All participants provided written informed consent prior to enrollment.

Author contributions

Study conception and design by Pan Y H, Lin J H; Experimental work and data collection by Chen Q H; Clinical sample collection by Yu Q J; Bioinformatics and statistical analysis by Zhai Q L; Manuscript drafting: Chen Q H, Zhai Q L, Yu Q J; and Critical revision and final approval by Pan Y H, Lin J H. All authors read and approved the final manuscript.

Use of large language models, AI and machine learning tools

No large language models, AI or machine learning tool was used for any part of the present study.

Conflict of interest

The authors declare no competing interests.

Data availability

The data generated in this study are available from the corresponding author upon reasonable request.References(45)

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