Toxic stress-specific cytoprotective responses regulate learned behavioral decisions in C. elegans

Gábor Hajdú,Csaba Sőti,István Taisz,Eszter Gecse,István Móra

doi:10.1186/s12915-021-00956-y

Gábor Hajdú, Csaba Sőti + Show 3 more

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https://doi.org/10.1186/s12915-021-00956-y

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Abstract

BackgroundRecognition of stress and mobilization of adequate “fight-or-flight” responses is key for survival and health. Previous studies have shown that exposure of Caenorhabditis elegans to pathogens or toxins simultaneously stimulates cellular stress and detoxification responses and aversive behavior. However, whether a coordinated regulation exists between cytoprotective stress responses and behavioral defenses remains unclear.ResultsHere, we show that exposure of C. elegans to high concentrations of naturally attractive food-derived odors, benzaldehyde and diacetyl, induces toxicity and food avoidance behavior. Benzaldehyde preconditioning activates systemic cytoprotective stress responses involving DAF-16/FOXO, SKN-1/Nrf2, and Hsp90 in non-neuronal cells, which confer both physiological (increased survival) and behavioral tolerance (reduced food avoidance) to benzaldehyde exposure. Benzaldehyde preconditioning also elicits behavioral cross-tolerance to the structurally similar methyl-salicylate, but not to the structurally unrelated diacetyl. In contrast, diacetyl preconditioning augments diacetyl avoidance, weakens physiological diacetyl tolerance, and does not induce apparent molecular defenses. The inter-tissue connection between cellular and behavioral defenses is mediated by JNK-like stress-activated protein kinases and the neuropeptide Y receptor NPR-1. Reinforcement of the stressful experiences using spaced training forms stable stress-specific memories. Memory retrieval by the olfactory cues leads to avoidance of food contaminated by diacetyl and context-dependent behavioral decision to avoid benzaldehyde only if there is an alternative, food-indicative odor.ConclusionsOur study reveals a regulatory link between conserved cytoprotective stress responses and behavioral avoidance, which underlies “fight-or-flight” responses and facilitates self-protection in real and anticipated stresses. These findings imply that variations in the efficiency of physiological protection during past episodes of stress might shape current behavioral decisions.Graphical abstract

Highlights

Recognition of stress and mobilization of adequate “fight-or-flight” responses is key for survival and health
Undiluted benzaldehyde and diacetyl induce food avoidance behavior and toxicity Low concentrations of food odors are attractive to C. elegans, whereas high concentrations induce an aversive response [22]
CcBA did not activate several other stress reporters, including the HSF-1 and DAF-16 target hsp-16.2, the HSF-1 target and endoplasmic reticulum unfolded protein response (UPR) reporter hsp-4, the SKN-1-dependent gcs-1, and the DAF-16dependent sod-3 reporter (Additional File 1: Fig. S3c). These findings demonstrate that a specific stress and detoxification response involving a subset of DAF-16- and SKN-1-activated genes participate in the molecular defense against ccBA toxicity

Summary

Introduction

Recognition of stress and mobilization of adequate “fight-or-flight” responses is key for survival and health. Adequate, coordinated responses of multicellular organisms are key to adapt to and overcome fundamental alterations of the environment [1, 2]. These responses originate from intracellular molecular defenses, such as the oxidative, xenobiotic, metabolic, and proteotoxic stress responses, which guard homeostasis and confer cytoprotection against the respective stresses, promoting physiological adaptation, fitness, and longevity at the organismal level [3]. Sensory cues representing danger evoke aversive behavior as a result of the perception of multiple sensory stimuli, neuronal processing, and decision-making both in humans and in other species [5, 6]. The neuroendocrine mechanisms of stress are extensively studied, the contribution of intracellular defenses to behavioral regulation is largely unknown

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