Abstract
BackgroundActivation of extracellular signal-regulated protein kinase (ERK), a member of mitogen-activated protein kinase (MAPK) family, has been proposed to mediate neurite outgrowth-promoting effects of several neurotrophic factors in vitro. However, the precise activity of ERK during axonal regeneration in vivo remains unclear. Peripheral axotomy has been shown to activate ERK in the cell bodies of primary afferent neurons and associated satellite cells. Nevertheless, whether ERK is also activated in the axons and surrounded Schwann cells which also play a key role in the regeneration process has not been clarified.ResultsPhosphorylation of ERK in the sciatic nerve in several time-points after crush injury has been examined. Higher phosphorylation of ERK was observed in the proximal and distal nerve stumps compared to the contralateral intact nerve from one day to one month after crush. The activation of ERK was mainly localized in the axons of the proximal segments. In the distal segments, however, active ERK was predominantly found in Schwann cells forming Bungner's bands.ConclusionThe findings indicate that ERK is activated in both the proximal and distal nerve stumps following nerve injury. The role of activated ERK in Wallerian degeneration and subsequent regeneration in vivo remains to be elucidated.
Highlights
Activation of extracellular signal-regulated protein kinase (ERK), a member of mitogen-activated protein kinase (MAPK) family, has been proposed to mediate neurite outgrowthpromoting effects of several neurotrophic factors in vitro
Activation of ERK in sciatic nerve after crush Levels of phosphorylated ERK (ERK-P) relative to those of total ERK (ERK-T) were elevated in the proximal nerve segment compared to the intact nerve in all time-points with statistically significant changes observed at week1 after crush (Figure 1)
ERK activation in axons and Schwann cells No positive immunoreactivity was observed when primary antibodies were omitted in the presence of either secondary antibodies conjugated with fluorescein isothiocyanate (FITC) or rhodamine (Figure 2A and 2B)
Summary
Activation of extracellular signal-regulated protein kinase (ERK), a member of mitogen-activated protein kinase (MAPK) family, has been proposed to mediate neurite outgrowthpromoting effects of several neurotrophic factors in vitro. Peripheral axotomy has been shown to activate ERK in the cell bodies of primary afferent neurons and associated satellite cells. Peripheral axotomy can activate several signaling pathways in neurons and associated glial cells leading to two opposing consequences: cell death or adaptation to regenerate neurites. MAPKs are a family of serine/threonine specific kinases that transduce extracellular stimuli to altered gene expression and have been shown to play a role in diverse cellular events ranging from proliferation, differentiation to apoptosis. Three subfamilies of MAPKs have been identified, namely: extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 kinase (p38). Inhibition of p38 leads to enhanced axonal regeneration, suggesting that p38 is likely involved in this process [12]
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