Quercetin, the new stress buster: Investigating the transcriptional and behavioral effects of this flavonoid on multiple stressors using Lymnaea stagnalis

Growing evidence suggests that a flavonoid-rich diet can prevent or reverse the effects of stressors, although the underlying mechanisms remain poorly understood. One common and abundant flavonoid found in numerous foods is quercetin. This study utilizes the pond snail Lymnaea stagnalis, a valid model organism for learning and memory, and a simple but robust learning paradigm—operant conditioning of aerial respiration—to explore the behavioral and transcriptional effects of different stressors on snails' cognitive functions and to investigate whether quercetin exposure can prevent stress effects on learning and memory formation. Our findings demonstrate that three different stressors—severe food deprivation, lipopolysaccharide injection (an inflammatory challenge), and fluoride exposure (a neurotoxic agent)—block memory formation for operant conditioning and affect the expression levels of key targets related to stress response, energy balance, and immune response in the snails' central ring ganglia. Remarkably, exposing snails to quercetin for 1 h before stress presentation prevents these effects at both the behavioral and transcriptional levels, demonstrating the potent stress-preventive properties of quercetin. Despite the evolutionary distance from humans, L. stagnalis has proven to be a valuable model for studying conserved mechanisms by which bioactive compounds like quercetin mitigate the adverse effects of various stressors on cognitive functions across species. Moreover, these findings offer insights into quercetin's potential for mitigating stress-induced physiological and cognitive impairments.