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Corazonin neurons function in sexually dimorphic circuitry that shape behavioral responses to stress in Drosophila.

Zhao Y, Bretz CA, Hawksworth SA, Hirsh J, Johnson EC - PLoS ONE (2010)

Bottom Line: Silencing and activation of corazonin neurons lead to differential lifespan under stress, and these effects showed a strong dependence on sex.Additionally, altered corazonin neuron physiology leads to fundamental differences in locomotor activity, and these effects were also sex-dependent.These results underscore the importance of central peptidergic processing within the context of stress and place corazonin signaling as a critical feature of neuroendocrine events that shape stress responses and may underlie the inherent sexual dimorphic differences in stress responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Wake Forest University, Winston-Salem, North Carolina, United States of America.

ABSTRACT
All organisms are confronted with dynamic environmental changes that challenge homeostasis, which is the operational definition of stress. Stress produces adaptive behavioral and physiological responses, which, in the Metazoa, are mediated through the actions of various hormones. Based on its associated phenotypes and its expression profiles, a candidate stress hormone in Drosophila is the corazonin neuropeptide. We evaluated the potential roles of corazonin in mediating stress-related changes in target behaviors and physiologies through genetic alteration of corazonin neuronal excitability. Ablation of corazonin neurons confers resistance to metabolic, osmotic, and oxidative stress, as measured by survival. Silencing and activation of corazonin neurons lead to differential lifespan under stress, and these effects showed a strong dependence on sex. Additionally, altered corazonin neuron physiology leads to fundamental differences in locomotor activity, and these effects were also sex-dependent. The dynamics of altered locomotor behavior accompanying stress was likewise altered in flies with altered corazonin neuronal function. We report that corazonin transcript expression is altered under starvation and osmotic stress, and that triglyceride and dopamine levels are equally impacted in corazonin neuronal alterations and these phenotypes similarly show significant sexual dimorphisms. Notably, these sexual dimorphisms map to corazonin neurons. These results underscore the importance of central peptidergic processing within the context of stress and place corazonin signaling as a critical feature of neuroendocrine events that shape stress responses and may underlie the inherent sexual dimorphic differences in stress responses.

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Corazonin neuronal alterations impact the levels of dopamine.Dopamine concentrations as determined by HPLC measurements on hemolymph derived from males and females with varying corazonin phenotypes. For females, only the Crz-rpr lines significantly differed in dopamine levels compared to all other control genotypes (P<0.05, Tukey's Post Test for means). In males, both the Crz-rpr and Crz-ork lines were significantly different than control parental genotypes.
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pone-0009141-g006: Corazonin neuronal alterations impact the levels of dopamine.Dopamine concentrations as determined by HPLC measurements on hemolymph derived from males and females with varying corazonin phenotypes. For females, only the Crz-rpr lines significantly differed in dopamine levels compared to all other control genotypes (P<0.05, Tukey's Post Test for means). In males, both the Crz-rpr and Crz-ork lines were significantly different than control parental genotypes.

Mentions: Given the observation that flies with altered corazonin neuronal function differ in their hyperactivity and normal locomotor activity profiles, we investigated the possibility that corazonin may be acting in concert with other hormones to shape these behavioral responses. One candidate transmitter that may be interacting with corazonin neurons is dopamine, based on previous descriptions of altered dopamine synthesis during stress and phenotypes associated with genetic differences in dopaminergic signaling [31]–[35]. We tested the possibility that dopamine signaling may be altered in the flies with genetically altered corazonin neuronal functions. We first tested this hypothesis through employing a receptor bioassay. Larval hemolymph derived from flies with specific corazonin neuronal alterations was applied to HEK-293 cells expressing the dopamine receptor encoded by CG9761 [36] and a luciferase reporter for cAMP [37] the second messenger through which this receptor signals. The amount of luminescence detected was greatest from hemolymph derived from flies lacking (rpr) followed by silenced (ork), w1118 and activated (NaChBac) corazonin neurons (Figure S4). While such results are indicative of an interaction between corazonin function and dopamine content, this measure only provides a relative measure of dopamine, as reporter-only transfected cells exhibited greater luminescence than vehicle treated cells, and for technical reasons only allowed investigation of larval stages. Therefore, we employed HPLC measurements on adult flies with altered corazonin neuronal function to quantify the impact of corazonin on dopamine levels (Figure 6). Dopamine levels were significantly higher in hemolymph derived from both males and females with ablated corazonin neurons. However, for the other genotypes there was also a strong dependence upon sex (P<0.0001, F = 33.44 Two-Way ANOVA). For males with silenced corazonin neurons, dopamine levels were also higher than parental genotypes. However, in females both activated and silenced corazonin cells have comparable dopamine levels as compared to parental genotypes. Since manipulations predicted to alter excitability of these neurons don't result in large or consistent changes in dopamine levels (see legend to Fig. 6), these manipulations may not fully block corazonin release. Notably, these effects were seen only in hemolymph samples, as brains derived from these different genotypes had dopamine levels that were not different than w1118 (data not shown). While dopamine levels change as a function of development, the most significant changes in dopamine levels occur coincident with eclosion and cuticular tanning, which are events that preceded these observations [38]. Additionally, we report similar patterns of altered dopamine levels in two different life stages, those of wandering third instar larva and adults, suggesting that altered dopamine levels are a specific consequence of corazonin neuronal manipulations.


Corazonin neurons function in sexually dimorphic circuitry that shape behavioral responses to stress in Drosophila.

Zhao Y, Bretz CA, Hawksworth SA, Hirsh J, Johnson EC - PLoS ONE (2010)

Corazonin neuronal alterations impact the levels of dopamine.Dopamine concentrations as determined by HPLC measurements on hemolymph derived from males and females with varying corazonin phenotypes. For females, only the Crz-rpr lines significantly differed in dopamine levels compared to all other control genotypes (P<0.05, Tukey's Post Test for means). In males, both the Crz-rpr and Crz-ork lines were significantly different than control parental genotypes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2818717&req=5

pone-0009141-g006: Corazonin neuronal alterations impact the levels of dopamine.Dopamine concentrations as determined by HPLC measurements on hemolymph derived from males and females with varying corazonin phenotypes. For females, only the Crz-rpr lines significantly differed in dopamine levels compared to all other control genotypes (P<0.05, Tukey's Post Test for means). In males, both the Crz-rpr and Crz-ork lines were significantly different than control parental genotypes.
Mentions: Given the observation that flies with altered corazonin neuronal function differ in their hyperactivity and normal locomotor activity profiles, we investigated the possibility that corazonin may be acting in concert with other hormones to shape these behavioral responses. One candidate transmitter that may be interacting with corazonin neurons is dopamine, based on previous descriptions of altered dopamine synthesis during stress and phenotypes associated with genetic differences in dopaminergic signaling [31]–[35]. We tested the possibility that dopamine signaling may be altered in the flies with genetically altered corazonin neuronal functions. We first tested this hypothesis through employing a receptor bioassay. Larval hemolymph derived from flies with specific corazonin neuronal alterations was applied to HEK-293 cells expressing the dopamine receptor encoded by CG9761 [36] and a luciferase reporter for cAMP [37] the second messenger through which this receptor signals. The amount of luminescence detected was greatest from hemolymph derived from flies lacking (rpr) followed by silenced (ork), w1118 and activated (NaChBac) corazonin neurons (Figure S4). While such results are indicative of an interaction between corazonin function and dopamine content, this measure only provides a relative measure of dopamine, as reporter-only transfected cells exhibited greater luminescence than vehicle treated cells, and for technical reasons only allowed investigation of larval stages. Therefore, we employed HPLC measurements on adult flies with altered corazonin neuronal function to quantify the impact of corazonin on dopamine levels (Figure 6). Dopamine levels were significantly higher in hemolymph derived from both males and females with ablated corazonin neurons. However, for the other genotypes there was also a strong dependence upon sex (P<0.0001, F = 33.44 Two-Way ANOVA). For males with silenced corazonin neurons, dopamine levels were also higher than parental genotypes. However, in females both activated and silenced corazonin cells have comparable dopamine levels as compared to parental genotypes. Since manipulations predicted to alter excitability of these neurons don't result in large or consistent changes in dopamine levels (see legend to Fig. 6), these manipulations may not fully block corazonin release. Notably, these effects were seen only in hemolymph samples, as brains derived from these different genotypes had dopamine levels that were not different than w1118 (data not shown). While dopamine levels change as a function of development, the most significant changes in dopamine levels occur coincident with eclosion and cuticular tanning, which are events that preceded these observations [38]. Additionally, we report similar patterns of altered dopamine levels in two different life stages, those of wandering third instar larva and adults, suggesting that altered dopamine levels are a specific consequence of corazonin neuronal manipulations.

Bottom Line: Silencing and activation of corazonin neurons lead to differential lifespan under stress, and these effects showed a strong dependence on sex.Additionally, altered corazonin neuron physiology leads to fundamental differences in locomotor activity, and these effects were also sex-dependent.These results underscore the importance of central peptidergic processing within the context of stress and place corazonin signaling as a critical feature of neuroendocrine events that shape stress responses and may underlie the inherent sexual dimorphic differences in stress responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Wake Forest University, Winston-Salem, North Carolina, United States of America.

ABSTRACT
All organisms are confronted with dynamic environmental changes that challenge homeostasis, which is the operational definition of stress. Stress produces adaptive behavioral and physiological responses, which, in the Metazoa, are mediated through the actions of various hormones. Based on its associated phenotypes and its expression profiles, a candidate stress hormone in Drosophila is the corazonin neuropeptide. We evaluated the potential roles of corazonin in mediating stress-related changes in target behaviors and physiologies through genetic alteration of corazonin neuronal excitability. Ablation of corazonin neurons confers resistance to metabolic, osmotic, and oxidative stress, as measured by survival. Silencing and activation of corazonin neurons lead to differential lifespan under stress, and these effects showed a strong dependence on sex. Additionally, altered corazonin neuron physiology leads to fundamental differences in locomotor activity, and these effects were also sex-dependent. The dynamics of altered locomotor behavior accompanying stress was likewise altered in flies with altered corazonin neuronal function. We report that corazonin transcript expression is altered under starvation and osmotic stress, and that triglyceride and dopamine levels are equally impacted in corazonin neuronal alterations and these phenotypes similarly show significant sexual dimorphisms. Notably, these sexual dimorphisms map to corazonin neurons. These results underscore the importance of central peptidergic processing within the context of stress and place corazonin signaling as a critical feature of neuroendocrine events that shape stress responses and may underlie the inherent sexual dimorphic differences in stress responses.

Show MeSH
Related in: MedlinePlus