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Effects and mechanism of epigallocatechin-3-gallate on apoptosis and mTOR/AKT/GSK-3β pathway in substantia nigra neurons in Parkinson rats

Neuroreport. 2019 Jan 16;30(2):60-65. doi: 10.1097/WNR.0000000000001149.

Abstract

The aim of this study is to investigate the protective effect of epigallocatechin-3-gallate (EGCG) on apoptosis and mTOR/AKT/GSK-3β pathway in substantia nigra neurons in 6-dopamine-induced Parkinson rats. A total of 30 healthy male SD rats were randomly divided into control group, the Parkinson model group, and Parkinson model+EGCG treatment group. The model and EGCG groups were injected into the right striatum with 6-OHDA to establish the Parkinson model, and the control group was injected with saline only. The EGCG group was intragastrically administered with EGCG 50 mg/kg daily for 4 weeks. The rats' turns, speed, and left forelimb usage; neuron apoptosis by TUNEL; and the α-synuclein protein expression in substantia nigra by immunohistochemical staining were studied. Western blotting was used to detect the relative protein (mTOR, AKT and GSK-3β) expressions. Compared with the model group, the EGCG group significantly reduced the rotation speed; increased the left forelimb usage (P<0.01); reduced the neuron apoptosis (P<0.01); decreased α-synuclein expression (P<0.01); and decreased the mTOR, AKT, and GSK-3β protein expressions (P<0.01). EGCG can reduce neuron cell apoptosis in substantia nigra neurons in 6-OHDA-induced Parkinson rats. The mechanism might be related to mTOR/AKT/GSK-3β activation.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Catechin / therapeutic use
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 beta / biosynthesis
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / biosynthesis
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / biosynthesis
  • Treatment Outcome
  • alpha-Synuclein / antagonists & inhibitors
  • alpha-Synuclein / biosynthesis

Substances

  • Neuroprotective Agents
  • alpha-Synuclein
  • Catechin
  • epigallocatechin gallate
  • mTOR protein, rat
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases