A dopamine receptor contributes to paraquat-induced neurotoxicity in Drosophila

Cassar, Marlène; Issa, Abdul-Raouf; Riemensperger, Thomas; Petitgas, Céline; Rival, Thomas; Coulom, Hélène; Iché-Torres, Magali; Han, Kuo; Birman, Serge

doi:10.1093/hmg/ddu430

Cited by 77 publications

(84 citation statements)

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“…Studies in Drosophila and mice reveal dopaminergic neurons are particularly susceptible to PQ toxicity, and implicate membrane NADPH oxidase as an important target for superoxide generation [46, 47]. Male Drosophila are more sensitive to behavioral disruptions by PQ, and mutations that increase dopamine levels ( Catsup ) conferred increased resistance, whereas mutations that decreased dopamine increased sensitivity [47, 48]. Notably, increased expression of dopamine receptor DAMB increased PQ sensitivity [48], and DAMB is expressed at higher levels in males.…”

Section: Discussionmentioning

confidence: 99%

“…Male Drosophila are more sensitive to behavioral disruptions by PQ, and mutations that increase dopamine levels ( Catsup ) conferred increased resistance, whereas mutations that decreased dopamine increased sensitivity [47, 48]. Notably, increased expression of dopamine receptor DAMB increased PQ sensitivity [48], and DAMB is expressed at higher levels in males. Therefore, one possibility is that Drosophila males are physiologically better-equipped to respond to PQ pre-treatment than females because of greater basal expression of PQ/superoxide sensitive pathways such as DAMB, while at the same time, this creates a greater target for toxic levels of PQ/superoxide stress.…”

Section: Discussionmentioning

confidence: 99%

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The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress

et al. 2017

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Summary Multiple human diseases involving chronic oxidative stress show a significant sex bias, including neurodegenerative diseases, cancer, immune dysfunction, diabetes, and cardiovascular disease. However a possible molecular mechanism for the sex-bias in physiological adaptation to oxidative stress remains unclear. Here we report that Drosophila melanogaster females but not males adapt to hydrogen peroxide stress, whereas males but not females adapt to paraquat (superoxide) stress. Stress adaptation in each sex required the conserved mitochondrial Lon protease and was associated with sex-specific expression of Lon protein isoforms and proteolytic activity. Adaptation to oxidative stress was lost with age in both sexes. Transgenic expression of transformer gene during development transformed chromosomal males into pseudo-females, and conferred the female-specific pattern of Lon isoform expression, Lon proteolytic activity induction and H2O2 stress adaptation; these effects were also observed using adult-specific transformation. Conversely, knockdown of transformer in chromosomal females eliminated the female-specific Lon isoform expression, Lon proteolytic activity induction and H2O2 stress adaptation, and produced the male-specific paraquat (superoxide) stress adaptation. Sex-specific expression of alternative Lon isoforms was also observed in mouse tissues. The results develop Drosophila melanogaster as a model for sex-specific stress adaptation regulated by the Lon protease, with potential implications for understanding sexual-dimorphism in human disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress

et al. 2017

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“…The assay was done according to Cassar et al (2015) with minor modifications. For a more detailed description see File S1.…”

Section: Food Intake Assay By Food Labelingmentioning

confidence: 99%

“…The experiment was repeated at least twice, with 30-80 flies per genotype and tested time point. Data were analyzed for statistical significance by two-tailed Fischer exact test.Paraquat resistance assay: application of paraquat on the nerve cordThe assay was done according to Cassar et al (2015) with minor modifications. For a more detailed description see File S1.…”

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confidence: 99%

Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

et al. 2015

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Maintenance of biological functions under negative energy balance depends on mobilization of storage lipids and carbohydrates in animals. In mammals, glucagon and glucocorticoid signaling mobilizes energy reserves, whereas adipokinetic hormones (AKHs) play a homologous role in insects. Numerous studies based on AKH injections and correlative studies in a broad range of insect species established the view that AKH acts as master regulator of energy mobilization during development, reproduction, and stress. In contrast to AKH, the second peptide, which is processed from the Akh encoded prohormone [termed "adipokinetic hormone precursor-related peptide" (APRP)] is functionally orphan. APRP is discussed as ecdysiotropic hormone or as scaffold peptide during AKH prohormone processing. However, as in the case of AKH, final evidence for APRP functions requires genetic mutant analysis. Here we employed CRISPR/Cas9-mediated genome engineering to create AKH and AKH plus APRP-specific mutants in the model insect Drosophila melanogaster. Lack of APRP did not affect any of the tested steroid-dependent processes. Similarly, Drosophila AKH signaling is dispensable for ontogenesis, locomotion, oogenesis, and homeostasis of lipid or carbohydrate storage until up to the end of metamorphosis. During adulthood, however, AKH regulates body fat content and the hemolymph sugar level as well as nutritional and oxidative stress responses. Finally, we provide evidence for a negative autoregulatory loop in Akh gene regulation.KEYWORDS Drosophila; adipokinetic hormone; adipokinetic hormone precursor-related peptide; energy homeostasis; stress resistance E NERGY homeostasis requires continuous compensation for fluctuations in the energy expenditure and availability of food resources. Organisms thus build up reserves under positive energy balance and catabolize them when the balance turns negative to retain stable levels of circulating energy fuel. Insulin signaling induces the uptake of excessive circulating sugars, thus promoting reserve accumulation (reviewed, e.g., in Saltiel and Kahn 2001; Cohen 2006), whereas energy mobilization is under the control of glucagon and glucocorticoid signaling in mammals (reviewed, e.g., in Rui 2014;Charron and Vuguin 2015) and adipokinetic hormone (AKH) signaling in insects (reviewed, e.g., in Van der Horst 2003;Lorenz and Gäde 2009;Bednářová et al. 2013a). Consistent with their fundamental physiological function in energy mobilization, AKHs are found not only in insects, but are common in Protostomia, where they have been identified both in Ecdyszoa (in Arthropoda, Tardigrada, and Priapulida) and Lophotrochozoa (in Mollusca, Rotifera, and Annelida) (Gäde 2009;Hauser and Grimmelikhuijzen 2014). Nevertheless, physiological functions of AKHs have been studied mainly in Arthropoda. Similar to mammals, also insects store lipids in the form of triacylglycerides (TGs) and as carbohydrates in the form of glycogen. The main storage organ for lipid and glycogen in insects is the fat body, which can thus b...

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“…) and damb (Cassar et al . ); and dd2r and der have been characterized previously (Ishimoto et al . ; Marella et al .…”

Section: Methodsmentioning

confidence: 99%

The mushroom body D1 dopamine receptor controls innate courtship drive

Lim

Fernández

Hinojos

et al. 2017

Genes Brain and Behavior

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Mating is critical for species survival and is profoundly regulated by neuromodulators and neurohormones to accommodate internal states and external factors. To identify the underlying neuromodulatory mechanisms, we investigated the roles of dopamine receptors in various aspects of courtship behavior in Drosophila. Here we report that the D1 dopamine receptor dDA1 regulates courtship drive in naïve males. The wild-type naïve males actively courted females regardless their appearance or mating status. On the contrary, the dDA1 mutant (dumb) males exhibited substantially reduced courtship toward less appealing females including decapitated, leg-less and mated females. The dumb male’s reduced courtship activity was due to delay in courtship initiation and prolonged intervals between courtship bouts. The dampened courtship drive of dumb males was rescued by reinstated dDA1 expression in the mushroom body α/β and γ neurons but not α/β or γ neurons alone, which is distinct from the previously characterized dDA1 functions in experience-dependent courtship or other learning and memory processes. We also found that the dopamine receptors dDA1, DAMB and dD2R are dispensable for associative memory formation and short-term memory of conditioned courtship, thus courtship motivation and associative courtship learning and memory are regulated by distinct neuromodulatory mechanisms. Taken together, our study narrows the gap in the knowledge of the mechanism that dopamine regulates male courtship behavior.

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A dopamine receptor contributes to paraquat-induced neurotoxicity in Drosophila

Cited by 77 publications

References 100 publications

The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress

The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress

Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

The mushroom body D1 dopamine receptor controls innate courtship drive

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