1α, 25 dihydroxyvitamin D₃-dependent up-regulation of calcium-binding proteins in motoneuron cells

Our standing of selective neuronal vulnerability as well as etiopathogenesis of sporadic neurodegerative diseases is extremely limited. In ALS, altered calcium homeostasis appears to contribute significantly to selective neuronal injury. Further in ALS, the absence of calcium binding proteins (calbindin-D(28K), parvalbumin, and calretinin) correlates with selective vulnerability and cell loss. In motoneuron cell culture models an ALS IgG-triggered and calcium-mediated destruction can be reversed by increased expression of calbindin-D(28K) following retroviral infection with calbindin-D(28K) cDNA. To increase calcium binding protein expression in motoneurons in vitro and in vivo, we have employed vitamin D₃. Forty-eight hr treatment of diffentiated VSC 4.1 cells with 0.1-30 nM 1,25 dihydroxyvitamin D₃ induced a two-fold increase in the immunoreactivity for calbindin-D(28K) and parvalbumin. Injection of 80-120 ng, 1,25 dihydroxyvitamin D₃ in the cerebral ventricles of adults rats also induced positive immunoreactivity in adult stage. These data suggest that analogs of 1,25 dihydroxyvitamin D₃ may be useful tools in enhancing the expression of calcium binding proteins in motor system and may have possible therapeutic value in neurodegenerative disease.