Mammalian target of rapamycin is required for axon growth of adult dorsal root ganglion neurons

Abstract

Different from neurons in the central nervous system, adult neurons in the mammalian peripheral nervous system can regenerate axons after injury partially by enhancing the intrinsic growth capacity. A conditioning lesion prior to the injury further enhances the regeneration. Previous studies about the roles of mammalian target of rapamycin complex 1 in affecting axon growth of neurons in dorsal root ganglions (DRGs) were controversial. Here we report that peripheral axotomy to dorsal root ganglions (DRGs) enhances AKT/mTOR activity, and PTEN deletion can partially mimic this growth promoting effect. Both pharmacological and genetic evidence indicate that PI3K/AKT/mTOR pathway is required for sensory axon regeneration. Moreover, we provide genetic evidence that mTORC1 is indispensible for axon regeneration in DRGs induced by either PTEN deletion or conditioning lesion. In addition, we find that Stat3 activation is also necessary for DRG axon growth, and predict mTORC1 can regulate the activation of Stat3. In a word, our study provide the genetic evidence that mTORC1 is required for axon growth in DRG neurons, and suggest some new interactions between PTEN-mTOR and JAK-STAT pathways.

Date of Award	2015
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology