mTOR signaling pathway differently regulates central and peripheral axon regeneration

Acta Biochim Biophys Sin (Shanghai). 2017 Aug 1;49(8):689-695. doi: 10.1093/abbs/gmx068.

Abstract

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.

Keywords: axon regeneration; central nervous systems; mTOR signaling; peripheral nervous systems.

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / physiology*
  • Cells, Cultured
  • Central Nervous System / cytology
  • Central Nervous System / metabolism*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Female
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / physiology
  • Immunosuppressive Agents / pharmacology
  • Mice, Inbred ICR
  • Nerve Regeneration / genetics
  • Nerve Regeneration / physiology*
  • Neurons / metabolism
  • Neurons / physiology
  • Peripheral Nervous System / cytology
  • Peripheral Nervous System / metabolism*
  • RNA Interference
  • Sensory Receptor Cells / metabolism
  • Sensory Receptor Cells / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Immunosuppressive Agents
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • Sirolimus