Intracellular phospholipase A(2) group IVA and group VIA play important roles in Wallerian degeneration and axon regeneration after peripheral nerve injury.
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.
López-Vales
Rubèn
R
Center for Research in Neuroscience, Research Institute of the McGill University Health Center, Montreal, Québec, Canada.
Navarro
Xavier
X
Shimizu
Takao
T
Baskakis
Constantinos
C
Kokotos
George
G
Constantinou-Kokotou
Violetta
V
Stephens
Daren
D
Dennis
Edward A
EA
David
Samuel
S
D000818:Animals; D001369:Axons / Q000201:enzymology / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005466:Fluorocarbons; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D054522:Group VI Phospholipases A2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007659:Ketones / Q000494:pharmacology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D023421:Models, Animal; D009416:Nerve Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D012867:Skin / Q000294:innervation; D014855:Wallerian Degeneration / Q000201:enzymology* / Q000473:pathology
C533806:1,1,1,2,2-pentafluoro-7-phenylheptan-3-one; D005466:Fluorocarbons; D007659:Ketones; D054513:Group IV Phospholipases A2; D054522:Group VI Phospholipases A2