Modulation of MAPK and Akt signaling pathways in proximal segment of injured sciatic nerves.

Mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K)/Akt-mediated signaling pathways play critical roles in peripheral nerve injury. However, the mechanism by which activate these signaling is unclear. We examined the activation of MAPK and Akt pathways in the proximal segments of crushed rat sciatic nerve after 1-30 days injury. We found that the phosphorylation level of Erk was attenuated in protein level. Phosphorylation of JNK and p38 increased from day 1 to day 15 following injury. In addition, activation of Akt was up-regulated predominantly in the ipsilateral proximal nerves and located in Schwann cells. Furthermore, phosphorylated GSK3β (Ser9) and GSK3β (Tyr216) were highly augmented from the third day to the 30th day and from 3 to 7 days after injury, respectively. Moreover, mTOR/p70S6 were activated within 7 days injury. Taken together, our studies suggest that the PI3K/Akt signaling is required for the regulation of axon regeneration in Schwann cells in the proximal nerve segments after injury. Furthermore, the contralateral nerves have some compensable response to the injury, at least, including the changes of signaling molecules.