Abstract
Purpose
To examine the specific changes that occur in the expression levels of extracellular vesicle-derived microRNAs (miRNAs) in intracranial cerebrospinal fluid (CSF) in moyamoya disease.
Methods
Patients with arteriosclerotic cerebral ischemia were used as controls to eliminate the effects of cerebral ischemia. Intracranial CSF was collected from moyamoya disease and control patients during bypass surgery. Extracellular vesicles (EVs) were extracted from the CSF. Comprehensive expression analysis of miRNAs extracted from EVs by next-generation sequencing (NGS) and validation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed.
Results
Experiments were conducted on eight cases of moyamoya disease and four control cases. In the comprehensive miRNA expression analysis, 153 miRNAs were upregulated, and 98 miRNAs were downregulated in moyamoya disease compared to the control cases (q-value < 0.05 and |log2 fold change|> 1). qRT-PCR performed on the four most variable miRNAs (hsa-miR-421, hsa-miR-361-5p, hsa-miR-320a, and hsa-miR-29b-3p) associated with vascular lesions among the differentially expressed miRNAs gave the same results as miRNA sequencing. On gene ontology (GO) analysis for the target genes, cytoplasmic stress granule was the most significant GO term.
Conclusions
This study is the first comprehensive expression analysis of EV-derived miRNAs in the CSF of moyamoya disease patients using NGS. The miRNAs identified here may be related to the etiology and pathophysiology of moyamoya disease.
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Data availability
The miRNA sequencing data are available in the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE193012.
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Funding
This work was funded by KAKENHI grants from the Japan Society for the Promotion of Science to Y. A. (no. 7118K08967) and K. Y. (no. 20K17961).
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This study protocol was carried out in accordance with the Declaration of Helsinki and with the approval of the Bioethics Review Board of Nagoya University Hospital (approval number 2020–0131). Written informed consent was obtained from all patients or responsible family members.
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Ota, S., Yokoyama, K., Kanamori, F. et al. Moyamoya disease-specific extracellular vesicle-derived microRNAs in the cerebrospinal fluid revealed by comprehensive expression analysis through microRNA sequencing. Acta Neurochir 165, 2045–2055 (2023). https://doi.org/10.1007/s00701-023-05579-6
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DOI: https://doi.org/10.1007/s00701-023-05579-6