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

• Published in: Neuroscience Vol. 379; pp. 281 - 291
• Main Authors: Zhu, Wen, Wang, Xue-Rui, Du, Si-Qi, Yan, Chao-Qun, Yang, Na-Na, Lin, Lu-Lu, Shi, Guang-Xia, Liu, Cun-Zhi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 21.05.2018
• Subjects: acupuncture; apoptosis; oxidative stress; thioredoxin; vascular dementia; DHE; NADPH; MWM; thioredoxin; ASK1; JNK; vascular dementia; DAPI; SOD; TrxR-1; apoptosis; Trx-1; VD; acupuncture; TUNEL; ROS; IF; oxidative stress
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2018.03.029

[Display omitted] •The expressions of Trx-1 and TrxR-1 were decreased in the hippocampus in VD rats.•Acupuncture ameliorated cognitive impairment and hippocampal neuronal damage.•Acupuncture up-regulated the hippocampal Trx-1 and TrxR-1 and inhibited the ASK1-JNK/p38 pathway.•Trx-1siRNA blocked the beneficial effects induced by acupuncture. 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.