Glatiramer promotes oligodendroglial cell maturation in a cuprizone-induced demyelination model.

The therapeutic potential of glatiramer acetate (GA) in Multiple Sclerosis has been apparent for many years and has been proven effective in experimental allergic encephalomyelitis, one of its animal models. The cuprizone (CPZ) model for the CNS de/remyelination has gained a renewed interest during the past decade. CPZ-induced demyelination is considered to be primarily an oligodendrocyte loss with participation of the inflammatory response. As the blood brain barrier remains intact, we found this model advantageous for studying GA effects on CNS remyelination with minimum influence of the peripheral immune cellular component. Our results show that GA, given one week before the CPZ treatment, had a maturational effect functional to remyelination. However, myelin was unorganized as compared to controls. When GA was concomitantly injected with CPZ, oligodendroglial precursor proliferation diminished in favor of maturation and myelin recovered an organized disposition. GA-treated animals also show microglial cell (MG) activation. In vitro assays demonstrated that GA-primed MG cultures had a significant increase in IL-10 and IL-4 secretion. GA-challenged MG-conditioned media induced oligodendrocyte proliferation and subsequent differentiation. Our results suggest that, in addition to its well-recognized immunoregulatory properties, GA also has an effect on resident immuno-response, which leads mature oligodendrocytes towards CPZ-induced demyelination repair.

Oligodendrogenesis in iron-deficient rats: effect of apotransferrin.

In rats, iron deficiency produces an alteration in myelin formation. However, there is limited information on the effects of this condition on oligodendroglial cell (OLGc) proliferation and maturation. In the present study, we further analyzed the hypomyelination associated with iron deficiency by studying the dynamics of oligodendrogenesis. Rats were fed control (40 mg Fe/kg) or iron-deficient (4 mg Fe/kg) diets from gestation day 5 until postnatal day 3 (P3) or 11 (P11). OLGc proliferation, migration and differentiation were investigated before and after an intracranial injection of apotransferrin at 3 days of age (P3). The proliferating cell population was evaluated at P3. Iron-deficient (ID) animals showed an increase in the oligodendrocyte precursors cell (OPC) population in comparison with controls. The overall pattern of migration of cells labeled with BrdU was investigated at P11. Iron deficiency increased the amount of BrdU(+) cells in the corpus callosum (CC) and decreased OLGc maturation and myelin formation. Changes in nerve conduction were analyzed by measuring visual evoked potentials. Latency and amplitude were significantly disturbed in ID rats compared with controls. Both parameters were substantially normalized when animals were treated with a single intracranial injection of 350 ng apotransferrin (aTf). The current results give support to the idea that iron deficiency increases the number of proliferating and undifferentiated cells in the CC compared with the control. Treatment with aTf almost completely reverted the effects of iron deficiency, both changing the migration pattern and increasing the number of mature cells in the CC and myelin formation.