Down-regulation of mu-opioid receptor expression in rat oligodendrocytes during their development in vitro.

Abstract

In the central nervous system, opioid receptors are found in neurons and also in glial cells. To gain more information on their presence and possibly on their function, we investigated the expression of mu-opioid receptors (MOR) during oligodendroglial cell development in two culture systems. In these models, during the first days, the cells are O-2A bipotential progenitor cells (also called OPCs; oligodendrocyte precursor cells), and then they differentiate into oligodendrocytes, which mature. In the first system, oligodendroglial cells, derived from newborn rat brain hemispheres, are grown in primary culture in the presence of a confluent layer of astrocytes, and they differentiate slowly. In the second, cells are specifically detached from the mixed cultures of the first system and are grown thereafter alone in secondary culture, a condition allowing a rapid cell differentiation. Under both conditions OPCs and immature oligodendrocytes were found to express a high level of MOR mRNA, whereas mature oligodendrocytes did not express it at all. The decrease of MOR expression during oligodendrocyte maturation was progressive, suggesting that it was not a primary effect of differentiation but an indirect secondary effect. Our study also shows that basic fibroblast growth factor (bFGF), which has been claimed by some authors to induce a dedifferentiation of the mature oligodendrocytes, and retinoic acid (RA), which had not been tested before, were not able to restore MOR expression in mature oligodendrocytes. These results indicate that bFGF and RA neither reverse the maturation process nor dedifferentiate the cells. However, RA was found to inhibit almost completely the expression of the myelin basic protein. The main result of this study is that MOR is expressed in progenitors and in immature oligodendrocytes, but not in mature oligodendrocytes. This suggests that MOR could be involved in some developmental process of the cells of the oligodendroglial lineage.