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Propofol Alleviates Depression-Like Behavior and Cognitive Disorder in Learned Helplessness Model Mice via Regulating
Jiarong Wang1, Jinchen Xiang1, Xuemei Han2
1School of Psychology and Mental Health, Hebei Key Laboratory of Mental Health and Brain Science, Tangshan Key Laboratory of Brain and Cognitive Neuroscience, North China University of Science and Technology, Tangshan, Hebei, China.
Journal of Neuroscience Research
|December 1, 2025
Summary
Propofol treatment improved depression-like behaviors in mice by enhancing the Notch signaling pathway and glutamate reuptake. This led to increased neurogenesis and synaptic plasticity, suggesting propofol as a potential novel antidepressant.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- Propofol, a widely used anesthetic, exhibits neuroprotective properties.
- Its potential antidepressant effects and underlying mechanisms require further investigation.
- Learned helplessness (LH) is a validated animal model for studying depression.
Purpose of the Study:
- To investigate the antidepressant effects of propofol in a learned helplessness mouse model.
- To elucidate the neurobiological mechanisms, including the Notch signaling pathway and glutamate system, involved in propofol's antidepressant action.
- To assess propofol's impact on hippocampal neurogenesis and synaptic plasticity.
Main Methods:
- Establishment of a learned helplessness depression model in adult male C57BL/6j mice.
- Behavioral assessments including sucrose preference, forced swim, tail suspension, and Morris water maze tests.
- Histological (HE staining, immunofluorescence) and molecular analyses (Western blotting, glutamate assay) of the hippocampus.
Main Results:
- The LH model mice displayed significant depressive behaviors, impaired spatial learning, and memory deficits.
- Neuronal death in the dentate gyrus, reduced neurogenesis, and impaired synaptic plasticity were observed in LH mice.
- Propofol treatment upregulated Notch signaling, improved glutamate reuptake, and enhanced hippocampal neurogenesis and synaptic plasticity.
Conclusions:
- Propofol demonstrates significant antidepressant efficacy in a learned helplessness mouse model.
- The antidepressant effects are mediated through the modulation of the Notch signaling pathway and glutamate system.
- These findings support propofol as a promising candidate for novel antidepressant drug development.
