ADAMTS-4 in oligodendrocytes contributes to myelination with an impact on motor function

Mathilde Pruvost1, Matthieu Lépine1, Camille Leonetti1

  • 1Normandie University, UNICAEN, INSERM, UMR-S 1237 Physiopathology and imaging of Neurological disorders, Cyceron, Caen 14000, France.

Glia
|August 30, 2017
PubMed

Insights

ADAMTS-4, an enzyme that degrades CSPGs, is crucial for normal myelination and motor function. Its absence in mice leads to abnormal myelination and motor deficits, highlighting its role in mature oligodendrocytes.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • Myelination is a critical late developmental process influenced by extracellular matrix components.
  • Chondroitin sulfate proteoglycans (CSPGs) are known inhibitors of myelination.
  • ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs type 4) degrades CSPGs, but its endogenous role is unclear.

Purpose of the Study:

  • To investigate the physiological functions of endogenous ADAMTS-4 in the central nervous system (CNS).
  • To determine the role of ADAMTS-4 in myelination and motor control.

Main Methods:

  • Utilized Adamts4/LacZ reporter mice to track ADAMTS-4 expression in the CNS.
  • Analyzed myelination in Adamts4 knockout (Adamts4-/-) mice.
  • Assessed motor deficits and nervous electrical activity in knockout mice.

Main Results:

  • ADAMTS-4 is highly expressed in CNS white matter, specifically in mature oligodendrocytes.
  • Adamts4-/- mice exhibit abnormal myelination, including increased axon diameter and altered g-ratio.
  • Lack of ADAMTS-4 results in motor deficits and impaired nervous electrical activity.

Conclusions:

  • ADAMTS-4 is identified as a novel marker of mature oligodendrocytes.
  • ADAMTS-4 plays a significant role in regulating myelination processes.
  • ADAMTS-4 contributes to the control of motor capacities through its influence on myelination.