Thyroid hormones promote differentiation of oligodendrocyte progenitor cells and improve remyelination after cuprizone-induced demyelination

FARNCO PG,SILVESTROFF L, SOTO AND PASQUINI JM

EXPERIMENTAL NEUROLOGY

Elsevier Inc

Año: 2008

0014-4886

In the present work we analyzed the capacity of thyroid hormones (THs) to improve remyelination using a  rat model of cuprizone-induced demyelination previously described in our laboratories. Twenty one days oldrat model of cuprizone-induced demyelination previously described in our laboratories. Twenty one days old  Wistar rats were fed a diet containing 0.6% cuprizone for two weeks to induce demyelination. After cuprizoneWistar rats were fed a diet containing 0.6% cuprizone for two weeks to induce demyelination. After cuprizone  withdrawal, rats were injected with triiodothyronine (T3). Histological studies carried out in these animalswithdrawal, rats were injected with triiodothyronine (T3). Histological studies carried out in these animals  revealed that remyelination in the corpus callosum (CC) of T3-treated rats improved markedly whenrevealed that remyelination in the corpus callosum (CC) of T3-treated rats improved markedly when  compared to saline treated animals. The cellular events occurring in the CC and in the subventricular zonecompared to saline treated animals. The cellular events occurring in the CC and in the subventricular zone  (SVZ) during the first week of remyelination were analyzed using specific oligodendroglial cell (OLGc)(SVZ) during the first week of remyelination were analyzed using specific oligodendroglial cell (OLGc)  markers. In the CC of saline treated demyelinated animals, mature OLGcs decreased and oligodendroglialmarkers. In the CC of saline treated demyelinated animals, mature OLGcs decreased and oligodendroglial  precursor cells (OPCs) increased after one week of spontaneous remyelination. Furthermore, the SVZ of theseprecursor cells (OPCs) increased after one week of spontaneous remyelination. Furthermore, the SVZ of these  animals showed an increase in early progenitor cell numbers, dispersion of OPCs and inhibition of Olig andanimals showed an increase in early progenitor cell numbers, dispersion of OPCs and inhibition of Olig and  Shh expression compared to non-demyelinated animals. The changes triggered by demyelination wereShh expression compared to non-demyelinated animals. The changes triggered by demyelination were  reverted after T3 administration, suggesting that THs could be regulating the emergence of remyelinatingreverted after T3 administration, suggesting that THs could be regulating the emergence of remyelinating  oligodendrocytes from the pool of proliferating cells residing in the SVZ. Our results also suggest that THsoligodendrocytes from the pool of proliferating cells residing in the SVZ. Our results also suggest that THs  receptor â mediates T3 effects on remyelination. These results support a potential role for THs in thereceptor â mediates T3 effects on remyelination. These results support a potential role for THs in the  remyelination process that could be used to develop new therapeutic approaches for demyelinating diseases.remyelination process that could be used to develop new therapeutic approaches for demyelinating diseases.