¹Chongqing Medical University the First Affiliated Hospital, Psychiatric Center, Chongqing, China

Background: Depression is a mental disorder with a high incidence and recurrence rate. In recent years, research on the pathogenesis of depression has mostly focused on adult patients, while the pathological mechanism during the critical period of neurodevelopment in adolescence and child remains unclear. The therapeutic effect of traditional depression drugs is limited and prone to recurrence. However, electroconvulsive therapy, as a physical treatment method used in clinical practice, has shown significant efficacy in patients with treatment-resistant depression and those at high suicide risk.

Aims & Objectives: This study, for the first time, took young mouse as the research subjects, constructed a young mouse depression model using chronic unpredictable mild stress modeling, and systematically evaluated its effects on oxidative stress and synaptic plasticity after electroconvulsive stimulation treatment. The study aims to reveal the regulatory effect of ECS on the neural mechanisms related to depression in childhood.

Method: Healthy male C57BL/6J mice aged 4 to 5 weeks were selected for the experiment and grouped by random number table method. The modeling group received CUMS modeling, including fasting, abstinence from drinking, and tail clamping and other stimuli. After the modeling was completed, the depressive-like behaviors of mice were evaluated through sugar water preference experiments, open field experiments and tail suspension experiments. Then, the electroconvulsive shock group received continuous ECS treatment. After these treatments are completed, behavioral assessments needs to be conducted again. After all the experiments, relevant brain tissues of mouse were collected, and the expression of synaptic associated proteins, such as synaptophysin, was detected by Western blotting and real-time fluorescence quantitative PCR. The levels of oxidative stress factors were detected using kits.

Results: In the comparative analysis of behavioral experimental results, the model group mice demonstrated poorer behavioral performance compared to the control group. These behavioral results fully demonstrated that the construction of the depressive-like behavior model was successful. Compared with the model group, the behavioral data of the treatment group showed significant improvements, indicating that ECS treatment effectively alleviated depressive-like behaviors in mice. The results of molecular biology experiments showed that compared with the control group, the expression levels of synaptic related proteins such as SYN in the model group were significantly decreased. Compared with the modeling group, the above results in the treatment group were significantly improved, suggesting that ECS can alleviate synaptic damage caused by depression modeling. Oxidative stress tests also showed the same results, which suggest that ECS can alleviate oxidative stress damage.

Discussion & Conclusions: CUMS modeling effectively induced depressive-like behavioral characteristics in young C57BL/6J mice. ECS treatment significantly improved depressive-like behaviors, enhanced the expression of synaptic associated proteins, and regulated the levels of oxidative stress factors.