Transcriptome analyses of brain arteries and microvessels in male and female mice reveal prominent olfactory receptor gene and protein expression

Abstract

We studied sex differences of large arteries (LAs: Circle of Willis, middle cerebral and basilar arteries) and microvessels (MVs: end arterioles, capillaries, and venules) in the brain circulation of young male/female C57Bl6/J mice and evaluated results using KEGG enrichment plots. Most surprising was the discovery of gene expression in KEGG olfactory transduction (olfactory receptors [ORs] and signaling pathways) which was predominant in LAs compared with MVs for both sexes, although expression was greater in males for most, but not all, ORs. Western blots demonstrated substantial protein levels of several ORs in both sexes. Immunofluorescence showed the prominent expression of ORs in the adventitia in a pattern resembling perivascular innervation. Female LAs manifested KEGG ribosome enrichment compared with male LAs. Also prominent in female LAs was upregulation of mitochondrial related genes as seen in KEGG Parkinson’s disease. Male MVs showed enhanced expression of KEGG neuroactive ligand receptor interaction whereas female MVs showed enhanced expression of KEGG intestinal immune network for IGA production. Male KEGG pathway MVs included numerous neurotransmitter receptor expression genes, whereas female MVs KEGG pathway promoted anti-inflammatory products. Our findings provide for further explorations of sex and segmental differences especially ORs affecting cerebral vascular function during health and disease.