Combination therapy of apo-transferrin and thyroid hormones enhances remyelination

MARÍA VICTORIA ROSATO-SIRI1 | LEANDRO NAZARENO MARZIALI1 | VANESA MATTERA1 | JORGE CORREALE2 | JUANA MARÍA PASQ

GLIA

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2020 vol. 69 p. 151 - 164

0894-1491

The current study presents two different approaches with a view to elucidating theinteraction between thyroid hormones (TH) and apo-transferrin (aTf) and their role inmyelination and remyelination. First, in vitro assays were conducted to determine thesingle and combined effects of aTf and triiodothyronine (T3) on oligodendroglial celllineage proliferation and oligodendrocyte (OLG) maturation in primary cultures.Results revealed higher proliferation rates upon single aTf treatment but Controlvalues upon T3 and aTf + T3 treatments. In addition, both aTf and T3 acceleratedOLG maturation, with the greatest effects being exerted by combined aTf + T3administration in terms of both myelin basic protein (MBP) expression and morphologicalcomplexity. Second, in vivo assays were carried out to establish single andcombined effects of aTf and T3, as well as TH receptor (THR) inhibitor I-850, onremyelination following a CPZ-induced demyelination protocol. Results showed anincrease in myelin deposition and the number of mature remyelinating OLG upon singletreatments, but a synergic effect upon combined aTf + T3 treatment which wasprevented by THR inhibition. It may be thus concluded that combined treatmentyielded the most beneficial effects on OLG maturation parameters in vitro and remyelinatingcapacity in vivo when compared to single treatments. These findings mayhelp explore the development of new target molecules in the treatment of demyelinatingdiseases.