Neurotoxic Effects and Mechanism of Arecoline on Locomotor Function in Caenorhabditis elegans as Model Organism

This study explored the effects of exposure to arecoline at different concentrations (0.5, 1, 2 and 4 mg/mL) on the locomotor capacity, intestinal barrier function, energy metabolism, oxidative stress and mitochondrial function of the model organism Caenorhabditis elegans, and it also revealed the neurotoxic mechanism of arecoline. The results showed that compared with the control group, exposure to 2 mg/mL arecoline significantly decreased the locomotor capacity of C. elegans (P < 0.001), disrupted the redox balance, resulted in lipofuscin accumulation (P < 0.01) and increased the average fluorescence intensity by 29.01%. Meanwhile, it damaged intestinal barrier integrity and affected energy metabolism (P < 0.001), decreasing the levels of glucose, pyruvate, citric acid and ATP by 36.94%, 43.11%, 37.76% and 55.88%, respectively. Additionally, arecoline exposure caused neuronal damage and significantly decreased neurotransmitter levels (P < 0.01), further confirming its neurotoxicity. It also decreased significantly the number of mitochondria in C. elegans (P < 0.05) and impaired mitochondrial function. In summary, 2 mg/mL arecoline exerts significant motor neurotoxicity in C. elegans mainly by disrupting intestinal barrier function, mediating reduced energy metabolism as well as oxidative stress, and ultimately resulting in reduced locomotor capacity and neuronal damage. These findings elucidate the mechanism of the motor neurotoxicity of arecoline, providing a theoretical basis for screening active substances that mitigates this neurotoxicity.