mTOR signaling pathway differently regulates central and peripheral axon regeneration.

Numerous studies have shown that the intrinsic axonal regenerative capacity of neurons differs between the peripheral and central nervous systems (CNSs). However, the molecular mechanisms controlling intrinsic axonal regenerative capacity are unclear. A better understanding of these mechanisms should aid in the development of effective therapeutic strategies for traumatic nervous system injury, including spinal cord injury. Here, we found that blocking mammalian target of rapamycin (mTOR) activity dramatically diminished axonal regrowth from embryonic cortical neurons. However, mTOR activity was not required for axonal regrowth from adult peripheral sensory neurons. By analyzing the levels of phospho-S6, a downstream target of mTOR, we found that embryonic cortical neurons had a much higher mTOR activity compared with adult peripheral sensory neurons. Our findings suggest that, in the CNS, the mTOR pathway plays a critical role in regulating the regenerative capacity of neurons, in contrast to the peripheral nervous system.