Phospholipase A2 plays an important role in myelin breakdown and phagocytosis during Wallerian degeneration.
Phospholipase A(2) (PLA(2)) hydrolyzes phosphatidylcholine to lysophosphatidylcholine and arachidonic acid. The former can induce myelin breakdown and the latter, via eicosanoids, can stimulate inflammatory responses. Immunohistochemical analysis of secreted (sPLA(2)) and cytosolic (cPLA(2)) forms of the enzyme was assessed in the injured adult rat sciatic and optic nerves. sPLA(2) and cPLA(2) are expressed in the first 2 weeks in the injured sciatic nerve, which correlates with rapid Wallerian degeneration in peripheral nerves. In contrast, both forms of PLA(2) were not expressed in the optic nerve for the first 3 weeks after crush injury, which correlates with slow Wallerian degeneration in the central nervous system (CNS). In addition, PLA(2) is not expressed in the lesioned sciatic nerve of C57BL/Wld(s) mutant mice in which Wallerian degeneration is severely retarded. Blocking cPLA(2) in the transected sciatic nerve of C57BL/6 mice, which have a naturally occurring null mutation for the major from of sPLA(2), resulted in a marked slowing of myelin and axonal degradation and phagocytosis in the distal nerve segment. These results provide direct evidence of an important role for cPLA(2) in Wallerian degeneration.
De
Susna
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Centre for Research in Neuroscience, McGill University, Montreal General Hospital Research Institute, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4.
Trigueros
Marcelino Avilés
MA
Kalyvas
Athena
A
David
Samuel
S
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001369:Axons / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D054501:Group II Phospholipases A2; D054513:Group IV Phospholipases A2; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D009186:Myelin Sheath / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D020221:Optic Nerve Injuries / Q000201:enzymology / Q000503:physiopathology; D010587:Phagocytosis / Q000235:genetics*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000201:enzymology / Q000503:physiopathology; D014855:Wallerian Degeneration / Q000201:enzymology* / Q000235:genetics
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; C081565:arachidonyltrifluoromethane; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2