ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Molecular Psychiatry
This article is part of the Research TopicFrom Molecular Changes to Behaviour: Exploring Neuropsychiatric DisordersView all 4 articles
SENP3/FIS1-Regulated PFC Neural Mitochondrial Fragmentation Underlies the Mechanism of Electroacupuncture Attenuating Depressive Behavior in CUMS Mice
Provisionally accepted
Shaoda Lai1
Xiaoke Qiu1
Peilin Lin1Jiayi Wu1Feifei Li1Ningjing Lai1Xin Li1Ting Tu1
Jiping Zhang1
Yong Huang1,2*
Zhinan Zhang1*- 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
- 2Southern Medical University Nanfang Hospital, Guangzhou, China
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Objective Electroacupuncture (EA) is a common alternative treatment for depression, but its underlying mechanism remains unclear. Research suggests that its therapeutic effect may involve reducing SENP3/FIS1-regulated mitochondrial fragmentation, thereby mitigating neuronal damage in the prefrontal cortex. This study aimed to evaluate the efficacy of EA at Baihui (GV20) and Yintang (GV29) on SENP3/FIS1-regulated mitochondrial fragmentation in prefrontal cortex neurons of depressive animals. Methods Twenty-eight 6-8-week-old male C57BL/6 mice were randomly divided into normal control, depression, and EA groups. Following depression modeling, the EA group received EA at GV20 and GV29. The effects of EA on neuronal mitochondrial fragmentation and the SENP3/FIS1 pathway were evaluated using transmission electron microscopy, western blotting, and immunofluorescence assays. Results EA at GV20 and GV29 notably reduced depression-like behaviors in animals and exerted neuroprotective effects on prefrontal cortical neurons. It also inhibited FIS1-mediated mitochondrial fragmentation in the prefrontal cortex and enhanced SUMOylation. Further investigation of SENP3, the key regulatory enzyme for FIS1 SUMOylation, revealed that EA downregulated the SENP3-FIS1 interaction. Conclusions These evidences suggested that the antidepressant effects of EA may involve modulation of mitochondrial fragmentation regulated by the SENP3/FIS1 pathway in prefrontal cortex neurons.
Keywords: Electroacupuncture, Depression, Prefrontal Cortex, Mitochondrial fragmentation, SENP3/FIS1
Received: 12 Jun 2025; Accepted: 05 Dec 2025.
Copyright: © 2025 Lai, Qiu, Lin, Wu, Li, Lai, Li, Tu, Zhang, Huang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yong Huang
Zhinan Zhang
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