Acupuncture ameliorates cognitive impairment and hippocampus neuronal loss in experimental vascular dementia through Nrf2-mediated antioxidant response.

Abstract

Emerging evidence suggests acupuncture could exert neuroprotection in the vascular dementia via anti-oxidative effects. However, the involvement of Nrf2, a master regulator of antioxidant defense, in acupuncture-induced neuroprotection in vascular dementia remains undetermined. The goal of our study was to investigate the contribution of Nrf2 in acupuncture and its effects on vascular dementia. Morris water maze and Nissl staining were used to assess the effect of acupuncture on cognitive function and hippocampal neurodegeneration in experimental vascular dementia. The distribution of Nrf2 in neurons in hippocampus, the protein expression of Nrf2 in both cytosol and nucleus, and the protein and mRNA levels of its downstream target genes NQO1 and HO-1 were detected by double immunofluorescent staining, Western blotting and realtime PCR analysis respectively. Cognitive function and microglia activation were measured in both wild-type and Nrf2 gene knockout mice after acupuncture treatment. We found that acupuncture could remarkably reverse the cognitive deficits, neuron cell loss, reactive oxygen species production, and decreased cerebral blood flow. It was notable that acupuncture enhanced nuclear translocation of Nrf2 in neurons and up-regulate the protein and mRNA levels of Nrf2 and its target genes HO-1 and NQO1. Moreover, acupuncture could significantly down-regulated the over-activation of microglia after common carotid artery occlusion surgery. However, the reversed cognitive deficits, neuron cell loss and microglia activation by acupuncture were abolished in Nrf2 gene knockout mice. In conclusion, these findings provide evidence that the neuroprotection of acupuncture in models of vascular dementia was via the Nrf2 activation and Nrf2-dependent microglia activation.

• Authors: Xue-Rui Wang, Guang-Xia Shi, Jing-Wen Yang, Chao-Qun Yan, Li-Ting Lin, Si-Qi Du, Wen Zhu, Tian He, Xiang-Hong Zeng, Qian Xu, Cun-Zhi Liu
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 89 Pg. 1077-84 (Dec 2015) ISSN: 1873-4596 [Electronic] United States
• PMID: 26546103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier Inc.

Chemical References

• Antioxidants
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Nfe2l2 protein, mouse
• RNA, Messenger
• Reactive Oxygen Species

Topics

• Acupuncture Therapy
• Animals
• Antioxidants (pharmacology)
• Apoptosis
• Blotting, Western
• Cells, Cultured
• Cognition Disorders (metabolism, pathology, prevention & control)
• Dementia, Vascular (metabolism, pathology, prevention & control)
• Fluorescent Antibody Technique
• Hippocampus (metabolism, pathology)
• Immunoenzyme Techniques
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NF-E2-Related Factor 2 (physiology)
• Neurons (metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• RNA, Messenger (genetics)
• Rats, Sprague-Dawley
• Reactive Oxygen Species
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction