Journal Article

Intracellular phospholipase A<sub>2</sub> group IVA and group VIA play important roles in Wallerian degeneration and axon regeneration after peripheral nerve injury

Rubèn López-Vales, Xavier Navarro, Takao Shimizu, Constantinos Baskakis, George Kokotos, Violetta Constantinou-Kokotou, Daren Stephens, Edward A. Dennis and Samuel David

in Brain

Published on behalf of The Guarantors of Brain

Volume 131, issue 10, pages 2620-2631
Published in print October 2008 | ISSN: 0006-8950
Published online August 2008 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awn188
Intracellular phospholipase A2 group IVA and group VIA play important roles in Wallerian degeneration and axon regeneration after peripheral nerve injury

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We provide evidence that two members of the intracellular phospholipase A2 family, namely calcium-dependent group IVA (cPLA2 GIVA) and calcium-independent group VIA (iPLA2 GVIA) may play important roles in Wallerian degeneration in the mouse sciatic nerve. We assessed the roles of these PLA2s in cPLA2 GIVA−/− mice, and mice treated with a selective inhibitor of iPLA2 GVIA (FKGK11). Additionally, the effects of both these PLA2s were assessed by treating cPLA2 GIVA−/− mice with the iPLA2 inhibitor. Our data suggest that iPLA2 GVIA may play more of a role in the early stages of myelin breakdown, while cPLA2 GIVA may play a greater role in myelin clearance by macrophages. Our results also show that the delayed myelin clearance and Wallerian degeneration after sciatic nerve crush injury in mice lacking cPLA2 and iPLA2 activities is accompanied by a delay in axon regeneration, target re-innervation and functional recovery. These results indicate that the intracellular PLA2s (cPLA2 GIVA and iPLA2 GVIA) contribute significantly to various aspects of Wallerian degeneration in injured peripheral nerves, which is then essential for successful axon regeneration. This work has implications for injury responses and recovery after peripheral nerve injuries in humans, as well as for understanding the slow clearance of myelin after CNS injury and its potential consequences for axon regeneration.

Keywords: axon regeneration; myelin; macrophage; phagocytosis; phospholipase A2; sciatic nerve injury

Journal Article.  7466 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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