Comparative description of the mRNA expression profile of Na+/K+-ATPase isoforms in adult mouse nervous system

Mutations in genes encoding Na+/K+-ATPase alpha 1, alpha 2, and alpha 3 subunits cause a wide range of disabling neurological disorders, and dysfunction of Na+/K+-ATPase may contribute to neuronal injury in stroke and dementia. To better understand the pathogenesis of these diseases, it is important to determine the expression patterns of the different Na+/K+-ATPase subunits within the brain and among specific cell types. Using two available scRNA-Seq databases from the adult mouse nervous system, we examined the mRNA expression patterns of the different isoforms of the Na+/K+-ATPase alpha, beta and Fxyd subunits at the single-cell level among brain regions and various neuronal populations. We subsequently identified specific types of neurons enriched with transcripts for alpha 1 and alpha 3 isoforms and elaborated how alpha 3-expressing neuronal populations govern cerebellar neuronal circuits. We further analyzed the co-expression network for alpha 1 and alpha 3 isoforms, highlighting the genes that positively correlated with alpha 1 and alpha 3 expression. The top 10 genes for alpha 1 were Chn2, Hpcal1, Nrgn, Neurod1, Selm, Kcnc1, Snrk, Snap25, Ckb and Ccndbp1 and for alpha 3 were Sorcs3, Eml5, Neurod2, Ckb, Tbc1d4, Ptprz1, Pvrl1, Kirrel3, Pvalb, and Asic2.