Friday, 20 March 2015

Microglia have to clear the debris before remyelination

Lampron A, Larochelle A, Laflamme N, Préfontaine P, Plante MM, Sánchez MG, Yong VW, Stys PK, Tremblay MÈ, Rivest S. Inefficient clearance of myelin debris by microglia impairs remyelinating processes. J Exp Med. 2015. pii: jem.20141656. [Epub ahead of print] An imbalance between remyelinating and demyelinating rates underlies degenerative processes in demyelinating diseases such as multiple sclerosis. An optimal therapeutic strategy would be to stimulate remyelination while limiting demyelination. Although accumulation of myelin debris impairs remyelination, the mechanisms regulating the clearance of such debris by mononuclear phagocytic cells are poorly understood. We demonstrate that after cuprizone intoxication, CCR2-dependent infiltration of mouse bone marrow-derived cells is abundant in demyelinating areas, but that these cells do not impact demyelination. However, in CX3CR1-deficient mice, the clearance of myelin debris by microglia was blocked greatly, affecting the integrity of the axon and myelin sheaths and thus preventing proper remyelination. These results highlight the crucial role played by CX3CR1 in myelin removal and show that there can be no efficient remyelination after a primary demyelinating insult if myelin clearance by microglia is impaired.

It is known that before remyelination can occur the debris from demyelination has to be cleared up. In some studies this occurs because of action of microglia, In this study they looked for things that influence the movement of micoglia and they focussed on the CX3C chemokine receptor 1 (CX3CR1) also known as the fractalkine receptor or G-protein coupled receptor 13 (GPR13) As the name suggests, this receptor binds the chemokine CX3CL1 (also called neurotactin or fractalkine).Fractalkine is a transmembrane protein and chemokine involved in the adhesion and migration of leukocytes. Fractalkine has also recently been discovered to play a developmental role in the migration of microglia in the central nervous system to their synaptic targets, where phagocytosis and synaptic refinement occur. CX3CR1 knockout mice had more synapses on cortical neurons than wild-type mice.CX3CR1 variants have been described to modify the survival time and the progression rate of patients with motor neuron disease.

No comments:

Post a Comment

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.