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

In the central nervous system, opioid receptors are found in neurons and al so in glial cells, To gain more information on their presence and possibly on their function, we investigated the expression of mu-opioid receptors (M OR) during oligodendroglial cell development in two culture systems. In the se models, during the first days, the cells are O-2A bipotential progenitor cells (also called OPCs; oligodendrocyte precursor cells), and then they d ifferentiate into oligodendrocytes, which mature. In the first system, olig odendroglial cells, derived from newborn rat brain hemispheres, are grown i n primary culture in the presence of a confluent layer of astrocytes, and t hey differentiate slowly. In the second, cells are specifically detached fr om the mixed cultures of the first system and are grown thereafter alone in secondary culture, a condition allowing a rapid cell differentiation. Unde r both conditions OPCs and immature oligodendrocytes were found to express a high level of MOR mRNA, whereas mature oligodendrocytes did not express i t at all. The decrease of MOR expression during oligodendrocyte maturation was progressive, suggesting that it was not a primary effect of differentia tion but an indirect secondary effect. Our study also shows that basic fibr oblast growth factor (bFGF), which has been claimed by some authors to indu ce a dedifferentiation of the mature oligodendrocytes, and retinoic acid (R A), which had not been tested before, were not able to restore MOR expressi on in mature oligodendrocytes. These results indicate that bFGF and RA neit her reverse the maturation process nor dedifferentiate the cells. However, RA was found to inhibit almost completely the expression of the myelin basi c protein. The main result of this study is that MOR is expressed in progen itors 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. J. Neurosci. Res. 60:10-20, 2000 . (C) 2000 Wiley-Liss, Inc.