Inhibition of MAPK ERK impairs axonal regeneration without an effect on neuronal loss after nerve injury.
Activation of extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase family, has been shown to mediate neurite outgrowth-promoting effects of various neurotrophic factors in vitro. Moreover, in vivo, ERK is activated in the primary sensory neurons and associated glial cells after nerve injury. However, the precise role of ERK in nerve regeneration remains unclear.


OBJECTIVE
This work was aimed to investigate the effects of ERK inhibition on axonal regeneration and neuronal loss after axotomy.


METHODS
Unilateral sciatic nerve crush was performed, and inhibition of ERK was achieved by intraperitoneal injection of 300 microg kg(-1) day(-1) of u0126 for 2 weeks in the inhibitor group. For the control group, only the vehicle was given with the same schedule.


RESULTS
ERK was activated in the crushed sciatic nerve, and this was significantly reduced by the inhibitor. In contrast, there was no activation of ERK in the L4/L5 spinal ganglia. Morphological analysis revealed the similar extent of neuronal loss in the two groups. In addition, the mean regeneration distance in the inhibitor group was lower than that of the control group.


CONCLUSIONS
These results suggest the crucial role of ERK in nerve regeneration but not sensory neuronal loss after trauma.
Peripheral Nerve Research Unit, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. fmedsat@md.chula.ac.th
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Agthong
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Koonam
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Kaewsema
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Chentanez
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D019771:Axotomy; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002452:Cell Count; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D016622:Silver Staining
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D048052:Mitogen-Activated Protein Kinase 3