Improvement of diabetes-induced spinal cord axon injury with taurine via nerve growth factor-dependent Akt/mTOR pathway

Amino Acids. 2024 Apr 18;56(1):32. doi: 10.1007/s00726-024-03392-8.

Abstract

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF-pAKT-mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway.

Keywords: Diabetes mellitus; Diabetic neuropathy; Nerve growth factor; Spinal cord axon injury; Taurine.

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / pathology
  • Diabetes Mellitus, Experimental* / metabolism
  • Nerve Growth Factor / genetics
  • Proto-Oncogene Proteins c-akt* / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Rats
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Taurine / metabolism
  • Taurine / pharmacology

Substances

  • mTOR protein, rat
  • Nerve Growth Factor
  • Proto-Oncogene Proteins c-akt
  • Taurine
  • TOR Serine-Threonine Kinases
  • Ngf protein, rat