Slc20a2 Deficiency Increases Susceptibility to CNS Demyelination Possibly Through Th17 Cells.

Primary familial brain calcification (PFBC) is a rare inherited neurodegenerative disorder characterized by abnormal brain calcium-phosphate (Ca-Pi) deposits along microvessels or inside neuronal cells. Eight genes have been linked to PFBC, with the SLC20A2 being the earliest identified. SLC20A2 encodes PiT-2, which is crucial for Pi homeostasis in the cerebrospinal fluid (CSF). In Slc20a2 homozygous knockout (HO) mice, the neurotoxic effects resulting from pathological CSF-Pi accumulation and the unique brain transcriptome suggested that the absence of PiT-2 might lead to myelin abnormalities. However, the myelin morphology and content under Slc20a2 deficiency remained largely unknown, and these were quantitatively investigated in this study. The results indicated no direct demyelination in the brains of Slc20a2-HO mice, but an increased susceptibility to demyelination under the induction of oligodendrocyte-toxic cuprizone (CPZ). The enhanced susceptibility was related to a greater infiltration of Th17 cells in the brain parenchyma, accompanying an exacerbation of brain calcification in Slc20a2 deficiency.