PTEN deletion promotes axon regeneration in DRGs through mTOR independent mechanisms

Abstract

Unlike the central nerve system (CNS), in the peripheral nervous system (PNS), neurons can regenerate their axons and reinnervate their targets. However, functional recovery often remains suboptimal. In this work, we investigated the role of PTEN-mTOR pathway during regeneration of peripheral neuronal axons in mice. We find that mTOR activity responds differently to injury in CNS and PNS. By deletion of PTEN, axonal growth capacity of PNS dorsal root ganglial neurons (DRGs) is enhanced both in vitro and in vivo. We also find that the enhanced axonal growth capacity of DRGs by PTEN knock out and conditioning lesion is independent of mTOR, while inhibiting PI3K and AKT activity can partially block both conditioning lesion effect and PTEN knock out induced growth. However just by knocking out PTEN is not sufficient to enhance the sensory recovery of the mice. Overall, these findings identify the difference in intrinsic regenerative mechanisms between CNS and PNS, and manipulation and fine control of PTEN-mTOR pathway are needed to benefit nerve repair.

Date of Award	2013
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology