期刊
GLIA
卷 65, 期 12, 页码 1961-1975出版社
WILEY
DOI: 10.1002/glia.23207
关键词
behaviour; metalloproteinase; myelination; oligodendrocyte; white matter
资金
- INSERM (French National Institute for Health and Medical Research)
- Universite Caen-Normandie
- Foundation for Medical Research [FRM/FDT20150532690]
- MESR (the French Ministry of High Education and Research)
- Agence Nationale de la Recherche [ANR-15-CE16-0010]
- Fonds Europeens de Developpement Economique et Regional (EU fundings-FEDER) Normandie
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.
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