EA Ameliorated Depressive Behaviors in CUMS Rats and Was Related to Its Suppressing Autophagy in the Hippocampus

Abstract

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 p<0.05), but these two therapies had nonsignificant difference between each other (p>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 (p<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.

Identification of key genes and crucial pathways for major depressive disorder using peripheral blood samples and chronic unpredictable mild stress rat models

“…In particular, we found that the mTOR, which is involved in the regulation of autophagy and inflammation signaling pathway ( Chu et al, 2020 ; Yao et al, 2020 ) was enriched. Further study found that mTOR signaling pathway is inhibited in CUMS rat model, which is in agreement with the results reported previously ( Zhang et al, 2020 ; Zhuo et al, 2020 ). SQSTM1, which was also upregulated in CUMS rat model, is associated with autophagy.…”

“…SQSTM1, which was also upregulated in CUMS rat model, is associated with autophagy. Moreover, the expression of LC3II was increased in the CUMS rat model, which is consistent with the results reported previously ( Zhang et al, 2020 ). Therefore, it is reasonable to speculate that SQSTM1 could play a crucial role through regulated autophagy in MDD.…”

Ginsenoside Rh2 administration produces crucial antidepressant‐like effects in a CUMS‐induced mice model of depression

“…The SPT is also commonly used to analyze depressive‐like behavior since this test provides information relating to anhedonia, one of the main depressive‐like symptoms (Goñi‐Balentziaga et al., 2018 ). As a widely applied animal model for depression, the CUMS model presents many core depressive behaviors, including helplessness, anhedonia, and reduced locomotor activity (Z. Zhang et al., 2020 ). In particular, K252a, a TrkB antagonist was injected into mice exposed to CUMS and completely blocked the BDNF‐TrkB signaling cascade.…”

A preliminary study on the diversity of butyrate-producing bacteria in response to the treatment of depression with Xiaoyaosan

“…2020; Zhang et al . 2020;), the CUMS modelling method was modified on the basis of Willner et al . to replicate the depression model (Willner et al .…”