Taurine inhibits neuron apoptosis in hippocampus of diabetic rats and high glucose exposed HT-22 cells via the NGF-Akt/Bad pathway

Amino Acids. 2020 Jan;52(1):87-102. doi: 10.1007/s00726-019-02810-6. Epub 2019 Dec 24.

Abstract

Type 2 Diabetes causes learning and memory deficits that might be mediated by hippocampus neuron apoptosis. Studies found that taurine might improve cognitive deficits under diabetic condition because of its ability to prevent hippocampus neuron apoptosis. However, the effect and mechanism is not clear. In this study, we explore the effect and mechanism of taurine on inhibiting hippocampus neuron apoptosis. Sixty male Sprague-Dawley rats were randomly divided into control, T2D, taurine treatment (giving 0.5%, 1%, and 2% taurine in drinking water) groups. Streptozotocin was used to establish the diabetes model. HT-22 cell (hippocampus neurons line) was used for in vitro experiments. Morris Water Maze test was used to check the learning and memory ability, TUNEL assay was used to measure apoptosis and nerve growth factor (NGF); Akt/Bad pathway relevant protein was detected by western blot. Taurine improved learning and memory ability and significantly decreased apoptosis of the hippocampus neurons in T2D rats. Moreover, taurine supplement also inhibited high glucose-induced apoptosis in HT-22 cell in vitro. Mechanistically, taurine increased the expression of NGF, phosphorylation of Trka, Akt, and Bad, as well as reduced cytochrome c release from mitochondria to cytosol. However, beneficial effects of taurine were blocked in the presence of anti-NGF antibody or Akt inhibitor. Taurine could inhibit hippocampus neuron apoptosis via NGF-Akt/Bad pathway. These results provide some clues that taurine might be efficient and feasible candidate for improvement of learning and memory ability in T2D rats.

Keywords: Akt/Bad pathway; Hippocampal apoptosis; Nerve growth factor (NGF); Taurine; Type 2 diabetes (T2D).

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Glucose / metabolism
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Humans
  • Maze Learning
  • Nerve Growth Factor / genetics*
  • Neurons / drug effects
  • Neurons / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Rats
  • Receptor, trkA / genetics*
  • Signal Transduction
  • Taurine / pharmacology*
  • bcl-Associated Death Protein / genetics

Substances

  • Bad protein, rat
  • Ngf protein, rat
  • bcl-Associated Death Protein
  • Taurine
  • Nerve Growth Factor
  • Receptor, trkA
  • Proto-Oncogene Proteins c-akt
  • Glucose