Intracellular phospholipase A(2) group IVA and group VIA play important roles in Wallerian degeneration and axon regeneration after peripheral nerve injury.

Abstract

We provide evidence that two members of the intracellular phospholipase A(2) family, namely calcium-dependent group IVA (cPLA(2) GIVA) and calcium-independent group VIA (iPLA(2) GVIA) may play important roles in Wallerian degeneration in the mouse sciatic nerve. We assessed the roles of these PLA(2)s in cPLA(2) GIVA(-/-) mice, and mice treated with a selective inhibitor of iPLA(2) GVIA (FKGK11). Additionally, the effects of both these PLA(2)s were assessed by treating cPLA(2) GIVA(-/-) mice with the iPLA(2) inhibitor. Our data suggest that iPLA(2) GVIA may play more of a role in the early stages of myelin breakdown, while cPLA(2) 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 cPLA(2) and iPLA(2) activities is accompanied by a delay in axon regeneration, target re-innervation and functional recovery. These results indicate that the intracellular PLA(2)s (cPLA(2) GIVA and iPLA(2) 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.

• Authors: Rubèn López-Vales, Xavier Navarro, Takao Shimizu, Constantinos Baskakis, George Kokotos, Violetta Constantinou-Kokotou, Daren Stephens, Edward A Dennis, Samuel David
• Journal: Brain : a journal of neurology (Brain) Vol. 131 Issue Pt 10 Pg. 2620-31 (Oct 2008) ISSN: 1460-2156 [Electronic] England
• PMID: 18718965 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 1,1,1,2,2-pentafluoro-7-phenylheptan-3-one
• Fluorocarbons
• Ketones
• Group IV Phospholipases A2
• Group VI Phospholipases A2

Topics

• Animals
• Axons (enzymology, physiology)
• Fluorescent Antibody Technique
• Fluorocarbons
• Group IV Phospholipases A2 (genetics, metabolism)
• Group VI Phospholipases A2 (antagonists & inhibitors, genetics, metabolism)
• Ketones (pharmacology)
• Macrophages (pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microscopy, Electron
• Models, Animal
• Nerve Regeneration (physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Sciatic Nerve (enzymology, injuries, pathology)
• Skin (innervation)
• Wallerian Degeneration (enzymology, pathology)