title: Role of mTOR in neuroprotection and axon regeneration after inflammatory stimulation.
abstract: Mature retinal ganglion cells (RGCs) do not normally regenerate injured axons, but degenerate after axotomy. However, inflammatory stimulation (IS) enables RGCs to survive axotomy and regenerate axons in the injured optic nerve. Similar effects are achieved by the genetic deletion of phosphatase and tensin homolog (PTEN) and subsequent mammalian target of rapamycin (mTOR) activation. Here, we report that IS prevents the axotomy-induced decrease of mTOR activity in RGCs in a CNTF/LIF-dependent manner. Inactivation of mTOR significantly reduced the number of long axons regenerating in the optic nerve, but surprisingly, did not affect the initial switch of RGCs into the regenerative state, or the neuroprotective effects associated with IS. In vitro, inhibition of mTOR activity reduced regeneration on myelin or chondroitin sulfate proteoglycans (CSPGs), but not on a growth-permissive substrate. Thus, mTOR activity is not generally required for neuroprotection or switching mature neurons into an active regenerative state, but it is important for the maintenance of the axonal growth state and overcoming of inhibitory effects caused by myelin and CSPGs.
authors.affiliation: Department of Neurology, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany
authors.forename: Marco
authors.initials: M
authors.lastname: Leibinger
authors.forename: Anastasia
authors.initials: A
authors.lastname: Andreadaki
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fischer
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D018696:Neuroprotective Agents; D020221:Optic Nerve Injuries / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D018696:Neuroprotective Agents; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases