The objective was to localize migraine-associated genes to neurovascular and glial cell types.

Although neurovascular involvement during a migraine attack is established, the roles of specific vascular cell types is not well appreciated. Furthermore, the etiology of the relationship between increased vascular risk and migraine remains unknown. Identifying the vascular cell types in which migraine-associated genes are expressed may inform on migraine pathophysiology and vascular risk.

Migraine-associated genes were localized in a single-cell RNA sequencing dataset of mouse brain neurovascular and glial cell types. Neurovascular cell types included pericytes, venous smooth muscle cells, arterial smooth muscle cells, arteriolar smooth muscle cells, capillary endothelial cells, venous endothelial cells, and arterial endothelial cells. Glial cell types included microglia, oligodendrocytes, and astrocytes. A minimum threshold for mRNA transcript expression was applied to include genes of possible biological importance. Permutation testing was performed to assess selective gene expression in each cell type.

Out of 110 migraine-associated genes, 69 met the threshold for expression and were included in the analysis. 42 genes (60.9%) were significantly enriched exclusively among neurovascular cells. 7 genes (10.1%) were significantly enriched exclusively among glial cells. 12 genes (17.4%) genes were significantly enriched across multiple neurovascular and glial cell types. 8 genes (11.6%) were not significantly enriched by any cell type. The 3 cell types that significantly enriched the most migraine-associated genes were pericytes (30 genes, 43.4%), venous smooth muscle cells (24, 34.8%), and arteriolar smooth muscle cells (16, 23.2%).

Migraine-associated genes are expressed in both neurovascular and glial cell types. Among neurovascular cell types, migraine-associated genes are enriched in a variety of arterial and venous cells, including endothelial cells, smooth muscle cells, and pericytes. These data support the multifaceted pathogenesis of migraine and suggest individual cell types for further investigation as well as possible targets for pharmacologic agents.