Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency

Ninety percent of Americans consume less than the USDA requirement of vitamin E (vitE). Proprioceptive deficits and degeneration of the somatosensory neuroanatomic tracts arising from the dorsal root ganglia are the canonical hallmarks of ataxia with vitE deficiency (AVED), but primary mechanisms remain unknown. Single-cell RNA-sequencing of DRG neurons (DRGNs) was performed in Ttpa-I- mice, an established model of AVED. In stark contrast to expected changes in proprioceptive neurons,Ttpa-I- DRGNs showed marked upregulation of voltage-gated Ca2+ and K+ channels in mechanosensitive, tyrosine-hydroxylase positive (TH+) DRGNs. Ensuing significant conductance changes resulted in reduced excitability in mechanosensitive Ttpa-I- DRGNs. A highly supplemented vitE diet prevented the cellular and molecular alterations and improved mechanosensation. VitE deficiency profoundly alters the molecular signature and functional properties of mechanosensitive TH+ DRGN, representing an intriguing shift of the prevailing paradigm from proprioception to mechanical sensation.