Date of Graduation
Selenium is a nutritionally essential trace element for mammals, and several studies have suggested that selenium may have an important function in the central nervous system. We hypothesized that selenium may play an important role in the differentiation of myelin producing cells, i.e., oligodendrocytes in developing brain. We employed an in vitro model system of glial cell cultures prepared from newborn rat brains to test this hypothesis. In mixed glial cell cultures, selenium deficiency inhibited developmental upregulation of myelin-specific genes, i.e., proteolipid protein (PLP), basic protein (BP) and myelin-associated glycoprotein (MAG) as assessed by Northern blot analysis. The effect of selenium was concentration dependent with an optimum of 30 nM. Staggered depletion and supplementation experiments showed that selenium deficiency during the early stages of oligodendrocyte development irreversibly prevents the upregulation of myelin-specific genes. Next, we employed purified oligodendrocyte cultures to determine whether selenium deficiency directly affects oligodendrocytes or the effects are mediated by astrocytes present in the mixed glial cultures. Various developmental stages of oligodendrocyte lineage cells were identified by Northern blot analysis in combination with indirect immunocytochemical staining technique. Both the expression of myelin-specific genes and the expression of oligodendrocyte-specific surface markers, i.e., O4 antibody reactivity and galactocerebrosides (GalC), were strongly inhibited in selenium-deprived purified oligodendrocyte cultures corroborating the findings from mixed glial cultures. In summary, the present study demonstrates that (a) selenium at the optimal concentration of 30 nM is required for normal differentiation and maturation of oligodendrocytes; (b) there is a critical period for selenium supplementation during the early stages of oligodendrocyte development; (c) the effect of selenium deficiency on oligodendrocyte differentiation may be related to impaired antioxidative defense mechanisms of the cells.
Gu, Jin, "Selenium requirement for oligodendrocyte differentiation." (1996). Graduate Theses, Dissertations, and Problem Reports. 8963.