Axonal regeneration after sciatic nerve lesion is delayed but complete in GFAP- and vimentin-deficient mice.
Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP(-/-)Vim(-/-) mice. After sciatic nerve crush in GFAP(-/-)Vim(-/-) mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics.
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Alexander
A
Berg
Johan
J
Zelano
Marcela
M
Pekna
Ulrika
U
Wilhelmsson
Milos
M
Pekny
Staffan
S
Cullheim
D000818:Animals; D001369:Axons / Q000473:pathology*; D019771:Axotomy; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000473:pathology; D009132:Muscles / Q000294:innervation; D009186:Myelin Sheath / Q000502:physiology; D009416:Nerve Regeneration; D020127:Recovery of Function; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013569:Synapses / Q000473:pathology; D015854:Up-Regulation; D014746:Vimentin / Q000172:deficiency* / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin