Mechanistic Study on Electroacupuncture-Regulated Circadian Autophagy for Inhibiting Ferroptosis in Hippocampal Neurons and Alleviating Depression-Like Behaviors in Adulthood Induced by Early Chronic Sleep Deprivation

Yuzhu Wu^1,2Xinwang Chen²Feixiang Liu^3,4Yanchen Feng⁵Ziyun Liao⁶Xinyu Bu⁷Wen Fu⁸Jing Gao⁸Lihua Wu¹Linyuan Fan⁹Qian Yang¹Penglin Yue¹Mengyu Wang^1*

• ¹School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, China
• ²College of Acupuncture, Moxibustion and Tuina, Henan University of Chinese Medicine, Zhengzhou, China
• ³Department of Neurology, Psychiatry and Psychology, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
• ⁴Henan Collaborative Innovation Center for the Prevention and Treatment of Major Diseases with Traditional Chinese and Western Medicine, Zhengzhou, China
• ⁵The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China
• ⁶Zhengzhou People's Hospital, Zhengzhou, China
• ⁷New Universe Acupuncture Inc, Pasadena City,California, United States
• ⁸The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
• ⁹The Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China

Abstract:Early-life chronic sleep deprivation (CSD) represents a significant risk factor for the development of adult depressive-like behaviors, although the precise molecular mechanisms underlying this association remain incompletely elucidated.In this study, we established a CSD rat model using a rodent sleep deprivation apparatus and employed behavioral tests to assess the effects of early electroacupuncture intervention on adult depressive-like behaviors. The underlying molecular mechanisms were systematically investigated through integrated experimental approaches including Prussian blue staining, transmission electron microscopy, enzyme-linked immunosorbent assay, and Western blot analysis.The experimental results demonstrated that the CSD group rats exhibited significant depressive-like behaviors, accompanied by pathological alterations such as increased iron deposition in hippocampal tissues and structural damage to neuronal mitochondria. Electroacupuncture intervention facilitated hippocampal neuronal repair and remodeling through multiple mechanisms, including the regulation of iron metabolism homeostasis, enhancement of antioxidant capacity, inhibition of ferroptosis, and suppression of excessive autophagy, thereby reversing the CSD-induced depressive-like behaviors.This study provides novel therapeutic strategies and mechanistic insights for the prevention and treatment of adult-onset depression induced by early-life chronic sleep deprivation.