Zhang Zhinan, Cai Xiaowen, Yao Zengyu, Wen Feng, Fu Zhiyi, Zhang Jiping, Zhong Zheng, Huang Yong, Qu Shanshan
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Neural Plast. 2020 Sep 22;2020:8860968. doi: 10.1155/2020/8860968. eCollection 2020.
Autophagy is confirmed to be involved in the onset and development of depression, and some antidepressants took effect by influencing the autophagic process. Electroacupuncture (EA), as a common complementary treatment for depression, may share the mechanism of influencing autophagy in the hippocampus like antidepressants. To investigate that, sixty Sprague-Dawley rats firstly went through chronic unpredictable mild stress (CUMS) model establishment, and 15 rats were assigned to a control group. After modeling, 45 successfully CUMS-induced rats were randomly divided to 3 groups: CUMS, selective serotonin reuptake inhibitor (SSRI), and EA groups (15 rats per group), to accept different interventions for 2 weeks. A sucrose preference test (SPT), weighing, and open field test (OFT) were measurement for depressive behaviors of rats. Transmission electron microscope (TEM), immunohistochemistry (IHC), and western blot analysis were used to evaluate the autophagic changes. After that, depression-like behaviors were successfully induced in CUMS models and reversed by SSRI and EA treatments (both < 0.05), but these two therapies had nonsignificant difference between each other ( > 0.05). Autolysosomes observed through TEM in the CUMS group were more than that in the control group. Their number and size in the SSRI and EA groups also decreased significantly. From IHC, the CUMS group showed enhanced positive expression of both Beclin1 and LC3 in CA1 after modeling ( < 0.05), and the LC3 level declined after EA treatments, which was verified by decreased LC3-II/LC3-I in western blot analysis. We speculated that CUMS-induced depression-like behavior was interacted with an autophagy process in the hippocampus, and EA demonstrated antidepressant effects by partly inhibiting autophagy with a decreased number of autolysosomes and level of LC3 along with LC3-II/LC3-I.
自噬被证实与抑郁症的发生和发展有关，一些抗抑郁药通过影响自噬过程发挥作用。电针（EA）作为抑郁症常见的辅助治疗方法，可能与抗抑郁药一样，通过影响海马体中的自噬机制发挥作用。为了探究这一点，首先将60只Sprague-Dawley大鼠建立慢性不可预测轻度应激（CUMS）模型，15只大鼠被分配到对照组。建模后，将45只成功诱导出CUMS的大鼠随机分为3组：CUMS组、选择性5-羟色胺再摄取抑制剂（SSRI）组和EA组（每组15只大鼠），接受不同干预2周。采用蔗糖偏好试验（SPT）、称重和旷场试验（OFT）测量大鼠的抑郁行为。使用透射电子显微镜（TEM）、免疫组织化学（IHC）和蛋白质免疫印迹分析来评估自噬变化。结果显示，CUMS模型成功诱导出抑郁样行为，SSRI和EA治疗可使其逆转（均P<0.05），但这两种疗法之间无显著差异（P>0.05）。通过TEM观察到，CUMS组的自噬体多于对照组。SSRI组和EA组的自噬体数量和大小也显著减少。从IHC结果来看，建模后CUMS组CA1区Beclin1和LC3的阳性表达均增强（P<0.05），EA治疗后LC3水平下降，蛋白质免疫印迹分析中LC3-II/LC3-I的降低证实了这一点。我们推测，CUMS诱导的抑郁样行为与海马体中的自噬过程相互作用，EA通过部分抑制自噬发挥抗抑郁作用，表现为自噬体数量减少以及LC3水平和LC3-II/LC3-I降低。
