Astro- versus microglia-enriched transcriptomes from aged Atxn2-CAG100-knockin mice suggest underlying pathology of RNA processing at ribosomes, and possibly at U-bodies [tRNAseq]

To understand these neurodegenerative disorders at the molecular level, the brains of 10-month-old Atxn2-CAG100-knockin mice were analyzed either as a whole or as microglial, astroglial (and neuronal) fractions via global RNA sequencing. Data was validated by comparison with spinal cord oligonucleotide microarray profile.

Here, glial fractions showed upregulation of Gpnmb (to 2082%), Cst7, Clec7a, Axl, Csf1, Lgals3, Lgals3bp, Slc11a1, and Usp18 as an unspecific neuroinflammatory signature, versus downregulation of the Nefh (to <19%), Scn4b, Camk2b, Rab15, and Grin1 synaptic mRNAs correlating with circuit disconnection. In all fractions, reductions of Kif5a, Rph3a, and Cplx1 were noted, versus disease-specific inductions of ribosomal subunits, presumably mirroring the partial loss-of-function of ATXN2 as RNA translation modulator.