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

2020 ◽  
Author(s):  
Gábor Hajdú ◽  
Eszter Gecse ◽  
István Taisz ◽  
István Móra ◽  
Csaba Sőti

AbstractBackgroundProtection of organismal integrity involve physiological stress responses and behavioral defenses. Recent studies in the roundworm Caenorhabditis elegans have shown that pathogen and toxin exposure simultaneously stimulate cellular stress and detoxification responses and aversive behavior. However, whether a coordinate regulation exists between cellular and neurobehavioral 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 aversive behavior. Benzaldehyde preconditioning activates systemic cytoprotective stress responses involving DAF-16/FOXO, SKN-1/Nrf and Hsp90 in somatic cells, which confer behavioral tolerance to benzaldehyde and cross-tolerance to the structurally similar methyl-salicylate, but not to the structurally unrelated diacetyl. In contrast, diacetyl preconditioning augments diacetyl avoidance and does not induce apparent molecular defenses. Reinforcement of the experiences using massed training forms relevant associative memories. Memory retrieval by the odor 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 findings reveal a regulatory link between physiological stress responses and learned behavior which facilitates self-protection in real and anticipated stresses. The potential conservation of this somato-neuronal connection might have relevance in maladaptive avoidant human behaviors.

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Gábor Hajdú ◽  
Eszter Gecse ◽  
István Taisz ◽  
István Móra ◽  
Csaba Sőti

Abstract Background Recognition 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. Results Here, 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. Conclusions Our 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


Author(s):  
Raz Bar-Ziv ◽  
Ashley E. Frakes ◽  
Ryo Higuchi-Sanabria ◽  
Theodore Bolas ◽  
Phillip A. Frankino ◽  
...  

2008 ◽  
Vol 16 (3) ◽  
pp. 112-115 ◽  
Author(s):  
Stephan Bongard ◽  
Volker Hodapp ◽  
Sonja Rohrmann

Abstract. Our unit investigates the relationship of emotional processes (experience, expression, and coping), their physiological correlates and possible health outcomes. We study domain specific anger expression behavior and associated cardio-vascular loads and found e.g. that particularly an open anger expression at work is associated with greater blood pressure. Furthermore, we demonstrated that women may be predisposed for the development of certain mental disorders because of their higher disgust sensitivity. We also pointed out that the suppression of negative emotions leads to increased physiological stress responses which results in a higher risk for cardiovascular diseases. We could show that relaxation as well as music activity like singing in a choir causes increases in the local immune parameter immunoglobuline A. Finally, we are investigating connections between migrants’ strategy of acculturation and health and found e.g. elevated cardiovascular stress responses in migrants when they where highly adapted to the German culture.


2019 ◽  
Vol 19 (4) ◽  
pp. 428-438 ◽  
Author(s):  
Nívea P. de Sá ◽  
Ana P. Pôssa ◽  
Pilar Perez ◽  
Jaqueline M.S. Ferreira ◽  
Nayara C. Fonseca ◽  
...  

<p>Background: The increasing incidence of invasive forms of candidiasis and resistance to antifungal therapy leads us to seek new and more effective antifungal compounds. </P><P> Objective: To investigate the antifungal activity and toxicity as well as to evaluate the potential targets of 2- cyclohexylidenhydrazo-4-phenyl-thiazole (CPT) in Candida albicans. </P><P> Methods: The antifungal activity of CPT against the survival of C. albicans was investigated in Caenorhabditis elegans. Additionally, we determined the effect of CPT on the inhibition of C. albicans adhesion capacity to buccal epithelial cells (BECs), the toxicity of CPT in mammalian cells, and the potential targets of CPT in C. albicans. </P><P> Results: CPT exhibited a minimum inhibitory concentration (MIC) value of 0.4-1.9 µg/mL. Furthermore, CPT at high concentrations (>60 x MIC) showed no or low toxicity in HepG2 cells and <1% haemolysis in human erythrocytes. In addition, CPT decreased the adhesion capacity of yeasts to the BECs and prolonged the survival of C. elegans infected with C. albicans. Analysis of CPT-treated cells showed that their cell wall was thinner than that of untreated cells, especially the glucan layer. We found that there was a significantly lower quantity of 1,3-β-D-glucan present in CPT-treated cells than that in untreated cells. Assays performed on several mutant strains showed that the MIC value of CPT was high for its antifungal activity on yeasts with defective 1,3-β-glucan synthase. </P><P> Conclusion: In conclusion, CPT appears to target the cell wall of C. albicans, exhibits low toxicity in mammalian cells, and prolongs the survival of C. elegans infected with C. albicans.</p>


Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 211-224 ◽  
Author(s):  
Joseph H Chou ◽  
Cornelia I Bargmann ◽  
Piali Sengupta

Abstract Caenorhabditis elegans odr-2 mutants are defective in the ability to chemotax to odorants that are recognized by the two AWC olfactory neurons. Like many other olfactory mutants, they retain responses to high concentrations of AWC-sensed odors; we show here that these residual responses are caused by the ability of other olfactory neurons (the AWA neurons) to be recruited at high odor concentrations. odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signaling proteins and is the founding member of a C. elegans gene family with at least seven other members. Alternative splicing of odr-2 yields three predicted proteins that differ only at the extreme amino terminus. The three isoforms have different promoters, and one isoform may have a unique role in olfaction. An epitope-tagged ODR-2 protein is expressed at high levels in sensory neurons, motor neurons, and interneurons and is enriched in axons. The AWC neurons are superficially normal in their development and structure in odr-2 mutants, but their function is impaired. Our results suggest that ODR-2 may regulate AWC signaling within the neuronal network required for chemotaxis.


2020 ◽  
Vol 32 (5) ◽  
pp. 1888-1898
Author(s):  
Melissa J. Hagan ◽  
Danielle S. Roubinov ◽  
W. Thomas Boyce ◽  
Nicole R. Bush

AbstractThere is emerging evidence that the development of problematic aggression in childhood may be associated with specific physiological stress response patterns, with both biological overactivation and underactivation implicated. This study tested associations between sex-specific patterns of stress responses across the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis and peer nominations of aggression among 271 kindergarten children (Mean age = 5.32 years; 52% Female; 44% White). Upon entry to kindergarten, children participated in a multidomain standardized stress paradigm. Changes in pre-ejection period (PEP) and salivary cortisol were assessed. On a separate day, children provided peer ratings of physical and relational aggression in a standardized interview. As expected, there was a significant three-way interaction between PEP, cortisol reactivity, and sex, but only for physical aggression. Among boys, cortisol reactivity was positively associated with physical aggression only for those with higher SNS reactivity. Findings suggest that for boys, asymmetrical and symmetrical HPA/SNS reactivity may be associated with lower and higher risk for peer-directed physical aggression, respectively. Understanding the complex associations between multisystem physiology, child sex and peer-directed aggression in early childhood may offer insight into individual differences underlying the emergence of behavioral dysregulation in early peer contexts.


Author(s):  
Govind Kannan ◽  
Zaira M Estrada-Reyes ◽  
Phaneendra Batchu ◽  
Brou Kouakou ◽  
Thomas H Terrill ◽  
...  

Abstract Social isolation can increase distress in goats, particularly when they cannot maintain visual contact with conspecifics. This experiment was conducted to determine the behavioral and physiological responses in goats during isolation with or without visual contact with conspecifics. Male Spanish goats (uncastrated, 8-mo old, average weight 29.4 ± 0.59 kg) were randomly assigned to a control (CO) group with no isolation or to one of four isolation treatment (TRT) pens (1.5 × 1.5 m) with: (1) open grill panels but with no visual contact with conspecifics (IO), (2) covered grill to prevent visual contact (IC), (3) open grill with visual contact (IV), or (3) covered grill with a 30 × 30 cm window to allow visual contact (IW) for 90 min of social isolation (n = 12 goats/TRT). Blood samples were collected at 0, 30, 60, and 90 min (Time) from isolated and control goats. The experiment was repeated one week later using the same animals, with each goat being subjected to the same isolation treatment the second time to study the effect of prior exposure to isolation. Friedman’s Two-Way ANOVA by Ranks Test in SAS showed that the median frequency of vocalization (rank score) in goats was high in IO group, low in IV and IW groups, and intermediate in IC group (P &lt; 0.01). Vocalization rank score was also higher (P &lt; 0.01) during the first 30 min of isolation in goats. Median frequency of visual contact was higher in the IW group than in the IV group (P &lt; 0.01). Frequency of climbing behavior was high in IC and IO groups, low in IV group, and intermediate in IW group (P &lt; 0.01). Repeated Measures Analysis using GLM procedures in SAS revealed that plasma cortisol and glucose concentrations tended (P &lt; 0.1) to be the highest in IO group than in CO, IC, IV, and IW groups. Cortisol levels were also higher (Time; P &lt; 0.05) at 0 and 90 min compared to 30 and 60 min. Norepinephrine concentrations decreased (P &lt; 0.05) with Time, and plasma non-esterified fatty acid (NEFA) levels were affected by TRT × Time interaction (P &lt; 0.01). Overall, epinephrine, norepinephrine, glucose, and NEFA concentrations were lower (P &lt; 0.01) and cortisol concentrations and lymphocyte counts higher (P &lt; 0.01) when goats were exposed to isolation the second time. The results showed that goats with no visual contact with conspecifics during social isolation had greater physiological stress responses and spent more time vocalizing or trying to escape the pen, which may indicate distress.


2021 ◽  
pp. 026988112097233
Author(s):  
Richard J Xia ◽  
Thomas Chao ◽  
Divya Patel ◽  
Gillinder Bedi

Background: Aspects of the canonical stress response differ in stimulant, opioid, and alcohol users relative to controls, and dysregulated responses to stress may contribute to continued use of these drugs. Little prior research has focused on stress responses in regular cannabis smokers. We assessed responses to a standardized laboratory social stress assay (the Trier Social Stress Task; TSST) in regular cannabis smokers (CANs) compared with controls (CONs). Methods: Healthy, non-treatment-seeking adult CANs (⩾4×/week; smoking cannabis as usual) and demographically matched CONs completed the TSST. Outcome measures were subjective mood, heart rate, and salivary cortisol. Results: Nineteen CANs (1 female) and 20 CONs (2 female) participated; groups were matched on trauma exposure, sex, race, and age. CANs smoked cannabis 6.4 ± 1.1 days/week. Eight CANs and one CON smoked tobacco cigarettes daily. Overall, the TSST produced expected increases in anxiety, negative mood states, cortisol, and heart rate. CANs had blunted subjective response to stress relative to CONs, but they did not differ in physiological (cortisol and cardiovascular) stress responding. Conclusion: These results indicate that CANs have blunted mood responses to social stress, but normative physiological stress responding. Observed differences could be due to residual effects of cannabis, reluctance to endorse negative mood states, or to issues related to identifying (i.e., emotional identification) or feeling (i.e., interoception) stress-related affective states. Further research is warranted to characterize the mechanisms of these differences and assess implications for daily functioning and treatment outcomes.


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