Combination therapy of apo-transferrin and thyroid hormones enhances remyelination

Abstract

The current study presents two different approaches with a view to elucidating the interaction between thyroid hormones (TH) and apo-transferrin (aTf) and their role in myelination and remyelination. First, in vitro assays were conducted to determine the single and combined effects of aTf and triiodothyronine (T3) on oligodendroglial cell lineage proliferation and oligodendrocyte (OLG) maturation in primary cultures. Results revealed higher proliferation rates upon single aTf treatment but Control values upon T3 and aTf + T3 treatments. In addition, both aTf and T3 accelerated OLG maturation, with the greatest effects being exerted by combined aTf + T3 administration in terms of both myelin basic protein (MBP) expression and morphological complexity. Second, in vivo assays were carried out to establish single and combined effects of aTf and T3, as well as TH receptor (THR) inhibitor I-850, on remyelination following a CPZ-induced demyelination protocol. Results showed an increase in myelin deposition and the number of mature remyelinating OLG upon single treatments, but a synergic effect upon combined aTf + T3 treatment which was prevented by THR inhibition. It may be thus concluded that combined treatment yielded the most beneficial effects on OLG maturation parameters in vitro and remyelinating capacity in vivo when compared to single treatments. These findings may help explore the development of new target molecules in the treatment of demyelinating diseases.