Enhanced Remyelination when ApoTransferrin and Thyroid Hormones are used together after a Cuprizone-Induced Demyelination

MATTERA, VANESA S; ROSATO-SIRI, V; MARZIALI, LN; CORREALE, J; PASQUINI, JM

Buenos aires

Simposio; The role of glia in health and disease of the nervous system.; 2017

IQUIFIB

Cuprizone (CPZ) feeding is an interesting model to investigate remyelinating therapies after demyelination. To further investigate the effects of thyroid hormones (THs) and Apo-Transferrin (aTf) on the remyelination process after CPZ-induced demyelination, Wistar rats were intoxicated with CPZ and treated with aTf, T3 or a combination of them during remyelination. The effect of TH receptor alpha (TRα) inhibitor I-850 was also studied. Although both T3 and aTf administration increased the number of mature oligodendrocytes (OLG), a stronger beneficial effect was observed for T3, and an even greater effect on OLG maturation was obtained through the combination of T3 and aTf. Finally, animals intranasally treated with I-850 showed decreased MBP immunostaining when compared to controls. Our results suggest that TH is necessary in early OLG development for aTf action, as exogenous aTf administration only, was unable to counteract the effect of low TH levels in the hypothyroid state at all the time points analyzed. Furthermore, the fact that hyperthyroidism induced an increase in Tf expression and aTf-dependent regulation of TRα strongly suggests that Tf could be involved in some of TH later effects on OLG maturation (Marziali et al., 2015). We conclude that the double treatment with aTf and TH is more efficient to promote remyelination when compared to single treatments, showing cooperative effects of these two well known pro-remyelinating factors. Furthermore, we show that TRα mediates the additive effects of both factors and opens the possibility of developing new molecules to target this receptor in multiple sclerosis (MS). Finally, our findings reinforce the hypothesis that more than one pathway has to be targeted to achieve proper remyelination in MS.