TY - JOUR T1 - Conditional deletion of the L-type calcium channel Cav1.2 in NG2 positive cells impairs remyelination in mice. JF - The Journal of Neuroscience JO - J. Neurosci. DO - 10.1523/JNEUROSCI.1787-17.2017 SP - 1787-17 AU - Diara A. Santiago González AU - Veronica T. Cheli AU - Norma N. Zamora AU - Tenzing N. Lama AU - Vilma Spreuer AU - Geoffrey G. Murphy AU - Pablo M. Paez Y1 - 2017/09/12 UR - http://www.jneurosci.org/content/early/2017/09/12/JNEUROSCI.1787-17.2017.abstract N2 - Exploring the molecular mechanisms that drive the maturation of oligodendrocyte progenitor cells (OPCs) during the remyelination process is essential to develop new therapeutic tools to intervene in demyelinating diseases such as Multiple Sclerosis. To determine whether L-type voltage-gated calcium channels (L-VGCCs) are required for OPC development during remyelination, we have generated an inducible conditional knockout mouse in which the L-VGCC isoform Cav1.2 was deleted in NG2 positive OPCs (Cav1.2KO). Using the cuprizone model of demyelination and mice of either sex we establish that Cav1.2 deletion in OPCs leads to less efficient remyelination of the adult brain. Specifically, Cav1.2KO OPCs mature slower and produce less myelin than control oligodendrocytes during the recovery period following cuprizone intoxication. This reduced remyelination was accompanied by an important decline in the number of myelinating oligodendrocytes and in the rate of OPC proliferation. Furthermore, during the remyelination phase of the cuprizone model, the corpus callosum of Cav1.2KO animals presented a significant decrease in the percentage of myelinated axons and a substantial increase in the mean g-ratio of myelinated axons compared to controls. Additionally, in a mouse line in which the Cav1.2KO OPCs were identified by a Cre reporter, we establish that Cav1.2KO OPCs display a reduced maturational rate through the entire remyelination process. These results suggest that Ca++ influx mediated by L-VGCCs in oligodendroglial cells is necessary for normal remyelination and is an essential Ca++ channel for OPC maturation during the remyelination of the adult brain. ER -