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

Abstract

Mutations in genes encoding Na⁺ /K⁺ -ATPase α1, α2, and α3 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 α, β 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 α1 and α3 isoforms and elaborated how α3-expressing neuronal populations govern cerebellar neuronal circuits. We further analyzed the co-expression network for α1 and α3 isoforms, highlighting the genes that positively correlated with α1 and α3 expression. The top 10 genes for α1 were Chn2, Hpcal1, Nrgn, Neurod1, Selm, Kcnc1, Snrk, Snap25, Ckb and Ccndbp1 and for α3 were Sorcs3, Eml5, Neurod2, Ckb, Tbc1d4, Ptprz1, Pvrl1, Kirrel3, Pvalb, and Asic2.