ADAMTS_4 in oligodendrocytes contributes to myelination with an impact on motor function

Authors
M Pruvost, M Lepine, C Leonetti, O Etard, M Naveau, V Agin, F Docagne, E Maubert, C Ali, E Emery, D Vivien

Lab
Physiopathology and imaging of Neurological disorders, GIP CYCERON, University of Caen Normandie, Bd Becquerel, BP 5229, 14074 Caen Cedex, France.

Journal
Glia

Abstract
Myelination is a late developmental process regulated by a set of inhibitory and stimulatory factors, including extracellular matrix components. Accordingly, chondroitin sulfate proteoglycans (CSPGs) act as negative regulators of myelination processes. A disintegrin and metalloproteinase with thrombospondin motifs type 4 (ADAMTS_4) is an extracellular protease capable of degrading CSPGs. Although exogenous ADAMTS_4 has been proven to be beneficial in several models of central nervous system (CNS) injuries, the physiological functions of endogenous ADAMTS_4 remain poorly understood. We first used Adamts4/LacZ reporter mice to reveal that ADAMTS_4 is strongly expressed in the CNS, especially in the white matter, with a cellular profile restricted to mature oligodendrocytes. Interestingly, we evidenced an abnormal myelination in Adamts4_/_ mice, characterized by a higher diameter of myelinated axons with a shifting g_ratio. Accordingly, lack of ADAMTS_4 is accompanied by motor deficits and disturbed nervous electrical activity. In conclusion, we demonstrate that ADAMTS_4 is a new marker of mature oligodendrocytes contributing to the myelination processes and thus to the control of motor capacities.

BIOSEB Instruments Used:
Aron Test or Four Plates Test (LE830),Rotarod (BX-ROD)