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脑源性神经营养因子信号通路:端粒酶基因敲除小鼠中针刺的调节作用

Brain-derived Neurotrophic Factor Signaling Pathway: Modulation by Acupuncture in Telomerase Knockout Mice.

作者信息

Lin Dong, Wu Qiang, Lin Xiaoyang, Borlongan Cesar V, He Zhi-Xu, Tan Jun, Cao Chuanhai, Zhou Shu-Feng

出版信息

Altern Ther Health Med. 2015 Nov-Dec;21(6):36-46.

PMID:26567448
Abstract

CONTEXT

Telomerase is a critical enzyme that is involved in aging and cancer and that is thought to be a part of multiple neurological diseases.

OBJECTIVE

To investigate the telomerase response in the brain to acupuncture, the study examined the levels of expression of brain-derived neurotrophic factor (BDNF) and its downstream signaling molecules, including tyrosine kinase receptor Β (TrkB), p75 neurotrophin receptor (p75NTR), protein kinase B (Akt), extracellular signal-regulated protein kinase (ERK1/2), and nuclear factor κΒ (NF-κΒ).

DESIGN

Both telomerase-deficient (Terc⁻/⁻) mice (Terc⁻/⁻ group) and normal, wild-type (WT) mice (WT group) were randomly assigned to 1 of 3 subgroups, 1 receiving acupuncture (acupuncture subgroup), 1 receiving sham acupuncture therapy (sham subgroup), and 1 receiving no treatment (control subgroup).

SETTING

The study occurred at the University of South Florida Health Byrd Alzheimer's Institute (Tampa, FL, USA).

INTERVENTION

The 2 acupuncture subgroups received acupuncture at the stomach 36 (ST-36) position for 30 min/d for 4 d. For the 2 sham groups, the sham point was set at a location approximately 3 mm to the lateral side of the tail on the gluteus muscle following the same schedule.

OUTCOME MEASURES

After 4 d, the mice were sacrificed, and the brain tissues were collected. The protein levels in the hippocampus and dentate gyrus (DG) of each mouse were determined by western blotting and immunostaining assays.

RESULTS

The Terc⁻/⁻ group showed downregulated hippocampal BDNF expression compared with the WT mice. Acupuncture at ST-36 for 4 d upregulated BDNF, TrkB, p75NTR, Akt, and ERK1/2 in the DG and hippocampus of the telomerase-deficient mice, but that result was not seen in the WT mice with normally functioning telomerase.

CONCLUSIONS

The use of acupuncture in pathologies associated with telomerase deficiencies, such as Alzheimer's disease (AD) and Parkinson's disease (PD), may provide some benefit in terms of eliciting better clinical responses. The research team believes that result occurs through the activation of BDNF and its downstream signaling pathways in populations of patients who exhibit low telomerase activity.

摘要

背景

端粒酶是一种关键酶,与衰老和癌症相关,并且被认为是多种神经疾病的一部分。

目的

为了研究大脑对针灸的端粒酶反应,该研究检测了脑源性神经营养因子(BDNF)及其下游信号分子的表达水平,包括酪氨酸激酶受体Β(TrkB)、p75神经营养因子受体(p75NTR)、蛋白激酶B(Akt)、细胞外信号调节蛋白激酶(ERK1/2)和核因子κΒ(NF-κΒ)。

设计

将端粒酶缺陷型(Terc⁻/⁻)小鼠(Terc⁻/⁻组)和正常野生型(WT)小鼠(WT组)随机分为3个亚组中的1组,1组接受针灸(针灸亚组),1组接受假针灸治疗(假手术亚组),1组不接受治疗(对照组)。

地点

该研究在美国佛罗里达州坦帕市南佛罗里达大学健康伯德阿尔茨海默病研究所进行。

干预

2个针灸亚组在足三里(ST-36)穴位进行针灸,每天一次,每次30分钟,共4天。对于2个假手术组,假穴位设置在臀大肌上尾巴外侧约3毫米处,按照相同的时间表进行。

观察指标

4天后,处死小鼠并收集脑组织。通过蛋白质印迹法和免疫染色法测定每只小鼠海马体和齿状回(DG)中的蛋白质水平。

结果

与WT小鼠相比,Terc⁻/⁻组海马体BDNF表达下调。在端粒酶缺陷型小鼠的DG和海马体中,在ST-36穴位针灸4天可上调BDNF、TrkB、p75NTR、Akt和ERK1/2,但在端粒酶功能正常的WT小鼠中未观察到该结果。

结论

在与端粒酶缺陷相关的疾病,如阿尔茨海默病(AD)和帕金森病(PD)中使用针灸,可能在引发更好的临床反应方面提供一些益处。研究团队认为,这一结果是通过激活端粒酶活性低的患者群体中的BDNF及其下游信号通路而产生的。

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