Anti-oxidative and Anti-apoptotic Effects of Acupuncture: Role of Thioredoxin-1 in the Hippocampus of Vascular Dementia Rats

Neuroscience. 2018 May 21:379:281-291. doi: 10.1016/j.neuroscience.2018.03.029. Epub 2018 Mar 26.

Abstract

Emerging evidence suggests that acupuncture treatment has anti-oxidative effects that affect cognitive impairment in vascular dementia (VD) rats. In the present study, we aimed to investigate whether thioredoxin-1 (Trx-1)/thioredoxin reductase-1 (TrxR-1) was involved in the beneficial effects of acupuncture. After 2-weeks of acupuncture treatment, Morris water maze (MWM), dihydroethidium (DHE) staining, Nissl staining and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to assess the effects of acupuncture on cognitive function and hippocampal neuronal injury in two-vessel occlusion (2VO) model. The protein and mRNA levels of Trx-1 and TrxR-1, the activity of TrxR-1 as well as the phosphorylation of the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 pathway were measured by Western blot, real-time PCR analysis, TrxR-1 activity analysis and immunofluorescence (IF) staining respectively. We found that there were oxidative and apoptotic injury in the CA1 area, accompanied with the decreased expressions of Trx-1 and TrxR-1 in the hippocampus. Acupuncture ameliorated cognitive deficits caused by cerebral ischemic injury and inhibited oxidative stress and neuronal apoptotic injury in the hippocampus. Acupuncture also up-regulated the expressions of Trx-1 and TrxR-1, increased the activity of TrxR-1, accompanied with inhibiting the activation of the ASK1-JNK/p38 pathway. However, the effects of acupuncture on improving cognitive function, inhibiting oxidative stress and neuron apoptotic damage were blocked by Trx-1siRNA. In conclusion, these findings indicated that acupuncture treatment improved VD though anti-oxidative and anti-apoptotic mechanisms which involved the up-regulations of Trx-1/TrxR-1 and inhibitions of ASK1-JNK/p38 pathway.

Keywords: acupuncture; apoptosis; oxidative stress; thioredoxin; vascular dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acupuncture Therapy*
  • Animals
  • Apoptosis / physiology*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / therapy
  • Dementia, Vascular / metabolism
  • Dementia, Vascular / pathology
  • Dementia, Vascular / therapy*
  • Disease Models, Animal
  • Hippocampus / metabolism*
  • Hippocampus / pathology*
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Kinase Kinase 5 / metabolism
  • Male
  • Maze Learning / physiology
  • Neurons / metabolism
  • Neurons / pathology
  • Oxidative Stress / physiology
  • Random Allocation
  • Rats, Wistar
  • Thioredoxin Reductase 1 / metabolism
  • Thioredoxins / antagonists & inhibitors
  • Thioredoxins / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Txn1 protein, rat
  • Thioredoxins
  • Thioredoxin Reductase 1
  • Txnrd1 protein, rat
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 5
  • MAP Kinase Kinase 4