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4 THE EFFECT OF TOLL-LIKE RECEPTOR AGONISTS ON SURVIVAL , DIFFERENTIATION AND MYELIN FORMATION BY OLIGODENDROCYTES MANUSCRIPT IN PREPARATION Malika Bsibsi

Toll-like receptors (TLRs) play a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules and endogenous proteins. In this study we investigated expression of TLRs in primary cultures of rat oligodendrocyte progenitor cells (OPCs) at different development stages as well as in mature oligodendrocytes. OPCs and mature oligodendrocytes were found to express high levels of mRNA encoding TLR2 and, to lesser extent, TLR3 and TLR4. In addition, we also investigated the effects of treatment with different TLR agonists on differentiation, maturation, survival and myelin formation by oligodendrocytes. In highly purified oligodendrocytes cultures zymosan and LPS promoted survival, differentiation and myelin sheet formation. Poly I:C, in contrast, was a potent inducer of oligodendrocyte death and inhibited myelin formation. Together, these data strongly suggest that TLRs in the brain play an important role in differentiation and myelination of oligodendrocytes, and not only in immune responses and injury.