TY - JOUR T1 - Loss of Tuberous Sclerosis Complex1 in Adult Oligodendrocyte Progenitor Cells Enhances Axon Remyelination and Increases Myelin Thickness after a Focal Demyelination JF - The Journal of Neuroscience JO - J. Neurosci. DO - 10.1523/JNEUROSCI.3454-16.2017 SP - 3454-16 AU - Lauren E. McLane AU - Jennifer N. Bourne AU - Angelina V. Evangelou AU - Luipa Khandker AU - Wendy B. Macklin AU - Teresa L. Wood Y1 - 2017/07/10 UR - http://www.jneurosci.org/content/early/2017/07/10/JNEUROSCI.3454-16.2017.abstract N2 - While the mammalian target of rapamycin (mTOR) is an essential regulator of developmental oligodendrocyte differentiation and myelination, oligodendrocyte-specific deletion of tuberous sclerosis complex (TSC), a major upstream inhibitor of mTOR, surprisingly also leads to hypomyelination during CNS development. However, the function of TSC has not been studied in the context of remyelination. Here, we utilized the inducible Cre-lox system to study the function of TSC in the remyelination of a focal, lysolecithin demyelinated lesion in adult male mice. Using two different mouse models in which Tsc1 is deleted by Cre expression in oligodendrocyte progenitor cells (OPCs) or in pre-myelinating oligodendrocytes, we reveal that deletion of Tsc1 affects oligodendroglia differently depending on the stage of the oligodendrocyte lineage. Tsc1 deletion from NG2+ OPCs accelerated remyelination. Conversely, Tsc1 deletion from PLP+ oligodendrocytes slowed remyelination. Contrary to developmental myelination, there were no changes in OPC or oligodendrocyte numbers in either model. Our findings reveal a complex role for TSC in oligodendrocytes during remyelination in which the timing of Tsc1 deletion is a critical determinant of its effect on remyelination. Moreover, our findings suggest that TSC has different functions in developmental myelination and remyelination.SIGNIFICANCE STATEMENTMyelin loss in demyelinating disorders such as multiple sclerosis results in disability due to loss of axon conductance and axon damage. Encouragingly, the nervous system is capable of spontaneous remyelination but this regenerative process often fails. Many chronically demyelinated lesions have oligodendrocyte progenitor cells (OPCs) within their borders. It is consequently of great interest to elucidate mechanisms by which we might enhance endogenous remyelination. Here we provide evidence that deletion of Tsc1 from OPCs, but not differentiating oligodendrocytes, is beneficial to remyelination. This finding contrasts with the loss of oligodendroglia and hypomyelination seen with Tsc1 or Tsc2 deletion in the oligodendrocyte lineage during CNS development and points to important differences in the regulation of developmental myelination and remyelination. ER -