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1.
Nat Commun ; 12(1): 4165, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230464

RESUMO

Insects use sex pheromones as a reproductive isolating mechanism to attract conspecifics and repel heterospecifics. Despite the profound knowledge of sex pheromones, little is known about the coevolutionary mechanisms and constraints on their production and detection. Using whole-genome sequences to infer the kinship among 99 drosophilids, we investigate how phylogenetic and chemical traits have interacted at a wide evolutionary timescale. Through a series of chemical syntheses and electrophysiological recordings, we identify 52 sex-specific compounds, many of which are detected via olfaction. Behavioral analyses reveal that many of the 43 male-specific compounds are transferred to the female during copulation and mediate female receptivity and/or male courtship inhibition. Measurement of phylogenetic signals demonstrates that sex pheromones and their cognate olfactory channels evolve rapidly and independently over evolutionary time to guarantee efficient intra- and inter-specific communication systems. Our results show how sexual isolation barriers between species can be reinforced by species-specific olfactory signals.


Assuntos
Comunicação , Drosophila/fisiologia , Feromônios/metabolismo , Atrativos Sexuais/fisiologia , Animais , Evolução Biológica , Copulação/fisiologia , Corte , Drosophila melanogaster/fisiologia , Feminino , Masculino , Filogenia , Comportamento Sexual Animal/fisiologia , Olfato/fisiologia , Especificidade da Espécie
2.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201772

RESUMO

Nucleolar stress occurs when ribosome production or function declines. Nucleolar stress in stem cells or progenitor cells often leads to disease states called ribosomopathies. Drosophila offers a robust system to explore how nucleolar stress causes cell cycle arrest, apoptosis, or autophagy depending on the cell type. We provide an overview of nucleolar stress in Drosophila by depleting nucleolar phosphoprotein of 140 kDa (Nopp140), a ribosome biogenesis factor (RBF) in nucleoli and Cajal bodies (CBs). The depletion of Nopp140 in eye imaginal disc cells generates eye deformities reminiscent of craniofacial deformities associated with the Treacher Collins syndrome (TCS), a human ribosomopathy. We show the activation of c-Jun N-terminal Kinase (JNK) in Drosophila larvae homozygous for a Nopp140 gene deletion. JNK is known to induce the expression of the pro-apoptotic Hid protein and autophagy factors Atg1, Atg18.1, and Atg8a; thus, JNK is a central regulator in Drosophila nucleolar stress. Ribosome abundance declines upon Nopp140 loss, but unusual cytoplasmic granules accumulate that resemble Processing (P) bodies based on marker proteins, Decapping Protein 1 (DCP1) and Maternal expression at 31B (Me31B). Wild type brain neuroblasts (NBs) express copious amounts of endogenous coilin, but coilin levels decline upon nucleolar stress in most NB types relative to the Mushroom body (MB) NBs. MB NBs exhibit resilience against nucleolar stress as they maintain normal coilin, Deadpan, and EdU labeling levels.


Assuntos
Nucléolo Celular/genética , Corpos Enovelados/patologia , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Ligação a RNA/genética , Estresse Fisiológico , Animais , Sistemas CRISPR-Cas , Corpos Enovelados/genética , Proteínas de Drosophila/antagonistas & inibidores , Drosophila melanogaster/fisiologia , Larva/genética , Larva/crescimento & desenvolvimento , Fosfoproteínas , Proteínas de Ligação a RNA/antagonistas & inibidores , Ribossomos/genética , Ribossomos/metabolismo
3.
Life Sci ; 281: 119758, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34175317

RESUMO

AIMS: The current lifestyle trend has made people vulnerable to diabetes and related diseases. Years of scientific research have not been able to yield a cure to the disease completely. The current study aims to investigate a link between high-fat diet mediated diabesity and circadian rhythm in the Drosophila model and inferences that might help in establishing a cure to the dreaded disease. MAIN METHODS: Several experimental methods including phenotypical, histological, biochemical, molecular, and behavioral assays were used in the study to detect obesity, diabetes, and changes in the circadian clock in the fly model. KEY FINDINGS: The larva and adults of Drosophila melanogaster exposed to high-fat diet (HFD) displayed excess deposition of fat as lipid droplets and micronuclei formation in the gut, fat body, and crop. Larva and adults of HFD showed behavioral defects. The higher amount of triglyceride, glucose, trehalose in the whole body of larva and adult fly confirmed obesity-induced hyperglycemia. The overexpression of insulin gene (Dilp2) and tribble (trbl) gene expression confirmed insulin resistance in HFD adults. We also observed elevated ROS level, developmental delay, altered metal level, growth defects, locomotory rhythms, sleep fragmentation, and expression of circadian genes (per, tim, and clock) in HFD larva and adults. Thus, HFD impairs the metabolism to produce obesity, insulin resistance, disruption of clock, and circadian clock related co-mordities in D. melanogaster. SIGNIFICANCE: The circadian gene expression provides an innovative perspective to understand and find a new treatment for type-II diabetes and circadian anomalies.


Assuntos
Comportamento Animal , Relógios Circadianos , Dieta Hiperlipídica , Drosophila melanogaster/fisiologia , Tecido Adiposo/metabolismo , Animais , Relógios Circadianos/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Feminino , Glucose/metabolismo , Hiperglicemia/metabolismo , Resistência à Insulina , Larva/metabolismo , Masculino , Metais/metabolismo , Obesidade/etnologia , Estresse Oxidativo , Distribuição Tecidual , Trealose/metabolismo
4.
Methods Mol Biol ; 2326: 47-54, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097260

RESUMO

Drosophila melanogaster, the fruit fly, has been widely used in biological investigation as an invertebrate alternative to mammals for its various advantages compared to other model organisms, which include short life cycle, easy handling, high prolificacy, and great availability of substantial genetic information. The behavior of Drosophila melanogaster is closely related to its growth, which can reflect the physiological conditions of Drosophila. We have optimized simple and robust behavioral assays for determining the larvae survival, adult climbing ability (mobility assay), reproductive behavior, and lifespan of Drosophila. In this chapter, we present the step-by-step detailed method for studying Drosophila behavior.


Assuntos
Drosophila melanogaster/fisiologia , Animais , Bioensaio/métodos , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Locomoção/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Masculino , Reprodução/efeitos dos fármacos , Testes de Toxicidade/métodos
5.
Nucleic Acids Res ; 49(13): 7644-7664, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34181727

RESUMO

Protein oligomerization is one mechanism by which homogenous solutions can separate into distinct liquid phases, enabling assembly of membraneless organelles. Survival Motor Neuron (SMN) is the eponymous component of a large macromolecular complex that chaperones biogenesis of eukaryotic ribonucleoproteins and localizes to distinct membraneless organelles in both the nucleus and cytoplasm. SMN forms the oligomeric core of this complex, and missense mutations within its YG box domain are known to cause Spinal Muscular Atrophy (SMA). The SMN YG box utilizes a unique variant of the glycine zipper motif to form dimers, but the mechanism of higher-order oligomerization remains unknown. Here, we use a combination of molecular genetic, phylogenetic, biophysical, biochemical and computational approaches to show that formation of higher-order SMN oligomers depends on a set of YG box residues that are not involved in dimerization. Mutation of key residues within this new structural motif restricts assembly of SMN to dimers and causes locomotor dysfunction and viability defects in animal models.


Assuntos
Proteínas do Complexo SMN/química , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Sequência Conservada , Dimerização , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiologia , Humanos , Locomoção , Modelos Moleculares , Mutação , Mutação Puntual , Domínios Proteicos , Multimerização Proteica , Proteínas do Complexo SMN/genética , Proteínas de Schizosaccharomyces pombe/química , Proteínas de Schizosaccharomyces pombe/genética
6.
Molecules ; 26(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068597

RESUMO

Research on nanomaterial exposure-related health risks is still quite limited; this includes standardizing methods for measuring metals in living organisms. Thus, this study validated an atomic absorption spectrophotometry method to determine fertility and bioaccumulated iron content in Drosophila melanogaster flies after feeding them magnetite nanoparticles (Fe3O4NPs) dosed in a culture medium (100, 250, 500, and 1000 mg kg-1). Some NPs were also coated with chitosan to compare iron assimilation. Considering both accuracy and precision, results showed the method was optimal for concentrations greater than 20 mg L-1. Recovery values were considered optimum within the 95-105% range. Regarding fertility, offspring for each coated and non-coated NPs concentration decreased in relation to the control group. Flies exposed to 100 mg L-1 of coated NPs presented the lowest fertility level and highest bioaccumulation factor. Despite an association between iron bioaccumulation and NPs concentration, the 500 mg L-1 dose of coated and non-coated NPs showed similar iron concentrations to those of the control group. Thus, Drosophila flies' fertility decreased after NPs exposure, while iron bioaccumulation was related to NPs concentration and coating. We determined this method can overcome sample limitations and biological matrix-associated heterogeneity, thus allowing for bioaccumulated iron detection regardless of exposure to coated or non-coated magnetite NPs, meaning this protocol could be applicable with any type of iron NPs.


Assuntos
Drosophila melanogaster/fisiologia , Comportamento Alimentar , Ferro/metabolismo , Nanopartículas de Magnetita/química , Animais , Bioacumulação , Quitosana/química , Fertilidade , Limite de Detecção , Nanopartículas de Magnetita/ultraestrutura , Eletricidade Estática , Difração de Raios X
7.
Methods Mol Biol ; 2322: 195-206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34043205

RESUMO

Drosophila melanogaster (Drosophila, fruit fly, or fly) is an important model organism in the studies of molecular genetic analysis and mechanism of Parkinson's disease (PD), benefiting from its powerful genetic tools and massive available genetic mutants. People have generated different fly models to mimic the inherited PDs and most of them have obvious mitochondrial abnormalities. Here, we describe some common approaches to analyze mitochondrial functions and morphological changes in Drosophila PD models.


Assuntos
Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Mitocôndrias/genética , Mitocôndrias/fisiologia , Animais , Modelos Animais de Doenças , Proteínas de Drosophila/genética , Testes Genéticos/métodos , Doença de Parkinson/genética , Doença de Parkinson/fisiopatologia
8.
Nat Commun ; 12(1): 2698, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976215

RESUMO

Gut microbiome profoundly affects many aspects of host physiology and behaviors. Here we report that gut microbiome modulates aggressive behaviors in Drosophila. We found that germ-free males showed substantial decrease in inter-male aggression, which could be rescued by microbial re-colonization. These germ-free males are not as competitive as wild-type males for mating with females, although they displayed regular levels of locomotor and courtship behaviors. We further found that Drosophila microbiome interacted with diet during a critical developmental period for the proper expression of octopamine and manifestation of aggression in adult males. These findings provide insights into how gut microbiome modulates specific host behaviors through interaction with diet during development.


Assuntos
Agressão/fisiologia , Drosophila melanogaster/fisiologia , Microbioma Gastrointestinal/fisiologia , Octopamina/metabolismo , Comportamento Sexual Animal/fisiologia , Animais , Bactérias/classificação , Bactérias/genética , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/fisiologia , Drosophila melanogaster/metabolismo , Drosophila melanogaster/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Masculino , Atividade Motora/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , RNA Ribossômico 16S/genética , Transdução de Sinais/fisiologia , Organismos Livres de Patógenos Específicos
9.
Nat Commun ; 12(1): 2943, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011945

RESUMO

Typical patterned movements in animals are achieved through combinations of contraction and delayed relaxation of groups of muscles. However, how intersegmentally coordinated patterns of muscular relaxation are regulated by the neural circuits remains poorly understood. Here, we identify Canon, a class of higher-order premotor interneurons, that regulates muscular relaxation during backward locomotion of Drosophila larvae. Canon neurons are cholinergic interneurons present in each abdominal neuromere and show wave-like activity during fictive backward locomotion. Optogenetic activation of Canon neurons induces relaxation of body wall muscles, whereas inhibition of these neurons disrupts timely muscle relaxation. Canon neurons provide excitatory outputs to inhibitory premotor interneurons. Canon neurons also connect with each other to form an intersegmental circuit and regulate their own wave-like activities. Thus, our results demonstrate how coordinated muscle relaxation can be realized by an intersegmental circuit that regulates its own patterned activity and sequentially terminates motor activities along the anterior-posterior axis.


Assuntos
Drosophila melanogaster/fisiologia , Interneurônios/fisiologia , Relaxamento Muscular/fisiologia , Animais , Animais Geneticamente Modificados , Neurônios Colinérgicos/citologia , Neurônios Colinérgicos/fisiologia , Drosophila melanogaster/anatomia & histologia , Interneurônios/citologia , Larva/anatomia & histologia , Larva/fisiologia , Locomoção/fisiologia , Modelos Neurológicos , Neurônios Motores/citologia , Neurônios Motores/fisiologia , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Optogenética
10.
Elife ; 102021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847264

RESUMO

Aneuploidy causes birth defects and miscarriages, occurs in nearly all cancers and is a hallmark of aging. Individual aneuploid cells can be eliminated from developing tissues by unknown mechanisms. Cells with ribosomal protein (Rp) gene mutations are also eliminated, by cell competition with normal cells. Because Rp genes are spread across the genome, their copy number is a potential marker for aneuploidy. We found that elimination of imaginal disc cells with irradiation-induced genome damage often required cell competition genes. Segmentally aneuploid cells derived from targeted chromosome excisions were eliminated by the RpS12-Xrp1 cell competition pathway if they differed from neighboring cells in Rp gene dose, whereas cells with normal doses of the Rp and eIF2γ genes survived and differentiated adult tissues. Thus, cell competition, triggered by differences in Rp gene dose between cells, is a significant mechanism for the elimination of aneuploid somatic cells, likely to contribute to preventing cancer.


Assuntos
Aneuploidia , Competição entre as Células , Drosophila melanogaster/fisiologia , Dosagem de Genes , Proteínas Ribossômicas/metabolismo , Animais , Drosophila melanogaster/crescimento & desenvolvimento , Humanos , Discos Imaginais/crescimento & desenvolvimento , Discos Imaginais/fisiologia , Neoplasias/genética
11.
Nat Commun ; 12(1): 2044, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824330

RESUMO

Simple innate behavior is often described as hard-wired and largely inflexible. Here, we show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity in Drosophila. First, we demonstrate that hot receptor neurons of the antenna and their molecular heat sensor, Gr28B.d, are essential for flies to produce escape turns away from heat. High-resolution fly tracking combined with a 3D simulation of the thermal environment shows that, in steep thermal gradients, the direction of escape turns is determined by minute temperature differences between the antennae (0.1°-1 °C). In parallel, live calcium imaging confirms that such small stimuli reliably activate both peripheral thermosensory neurons and central circuits. Next, based on our measurements, we evolve a fly/vehicle model with two symmetrical sensors and motors (a "Braitenberg vehicle") which closely approximates basic fly thermotaxis. Critical differences between real flies and the hard-wired vehicle reveal that fly heat avoidance involves decision-making, relies on rapid learning, and is robust to new conditions, features generally associated with more complex behavior.


Assuntos
Drosophila melanogaster/fisiologia , Resposta Táctica/fisiologia , Animais , Comportamento Animal , Comportamento de Escolha , Drosophila melanogaster/genética , Imageamento Tridimensional , Sensação Térmica/fisiologia
12.
Nature ; 592(7854): 414-420, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33828296

RESUMO

Critical periods-brief intervals during which neural circuits can be modified by activity-are necessary for proper neural circuit assembly. Extended critical periods are associated with neurodevelopmental disorders; however, the mechanisms that ensure timely critical period closure remain poorly understood1,2. Here we define a critical period in a developing Drosophila motor circuit and identify astrocytes as essential for proper critical period termination. During the critical period, changes in activity regulate dendrite length, complexity and connectivity of motor neurons. Astrocytes invaded the neuropil just before critical period closure3, and astrocyte ablation prolonged the critical period. Finally, we used a genetic screen to identify astrocyte-motor neuron signalling pathways that close the critical period, including Neuroligin-Neurexin signalling. Reduced signalling destabilized dendritic microtubules, increased dendrite dynamicity and impaired locomotor behaviour, underscoring the importance of critical period closure. Previous work defined astroglia as regulators of plasticity at individual synapses4; we show here that astrocytes also regulate motor circuit critical period closure to ensure proper locomotor behaviour.


Assuntos
Astrócitos/fisiologia , Período Crítico Psicológico , Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Vias Eferentes/fisiologia , Neurônios Motores/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Moléculas de Adesão Celular Neuronais/metabolismo , Dendritos/fisiologia , Feminino , Locomoção/fisiologia , Masculino , Microtúbulos/metabolismo , Neurópilo/fisiologia , Receptores de Superfície Celular/metabolismo , Transdução de Sinais , Sinapses/fisiologia , Fatores de Tempo
13.
Elife ; 102021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885361

RESUMO

Vertebrate macrophages are a highly heterogeneous cell population, but while Drosophila blood is dominated by a macrophage-like lineage (plasmatocytes), until very recently these cells were considered to represent a homogeneous population. Here, we present our identification of enhancer elements labelling plasmatocyte subpopulations, which vary in abundance across development. These subpopulations exhibit functional differences compared to the overall population, including more potent injury responses and differential localisation and dynamics in pupae and adults. Our enhancer analysis identified candidate genes regulating plasmatocyte behaviour: pan-plasmatocyte expression of one such gene (Calnexin14D) improves wound responses, causing the overall population to resemble more closely the subpopulation marked by the Calnexin14D-associated enhancer. Finally, we show that exposure to increased levels of apoptotic cell death modulates subpopulation cell numbers. Taken together this demonstrates macrophage heterogeneity in Drosophila, identifies mechanisms involved in subpopulation specification and function and facilitates the use of Drosophila to study macrophage heterogeneity in vivo.


Assuntos
Apoptose , Drosophila melanogaster/fisiologia , Macrófagos/fisiologia , Animais , Apoptose/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Expressão Gênica , Larva/crescimento & desenvolvimento , Larva/fisiologia , Pupa/crescimento & desenvolvimento , Pupa/fisiologia
14.
Elife ; 102021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33902813

RESUMO

Oncogenes often promote cell death as well as proliferation. How oncogenes drive these diametrically opposed phenomena remains to be solved. A key question is whether cell death occurs as a response to aberrant proliferation signals or through a proliferation-independent mechanism. Here, we reveal that Src, the first identified oncogene, simultaneously drives cell proliferation and death in an obligatorily coupled manner through parallel MAPK pathways. The two MAPK pathways diverge from a lynchpin protein Slpr. A MAPK p38 drives proliferation whereas another MAPK JNK drives apoptosis independently of proliferation signals. Src-p38-induced proliferation is regulated by methionine-mediated Tor signaling. Reduction of dietary methionine uncouples the obligatory coupling of cell proliferation and death, suppressing tumorigenesis and tumor-induced lethality. Our findings provide an insight into how cells evolved to have a fail-safe mechanism that thwarts tumorigenesis by the oncogene Src. We also exemplify a diet-based approach to circumvent oncogenesis by exploiting the fail-safe mechanism.


Assuntos
Morte Celular , Proliferação de Células , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiologia , Metionina/deficiência , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Larva/genética , Larva/crescimento & desenvolvimento , Larva/fisiologia , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
15.
Nature ; 593(7858): 244-248, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33911283

RESUMO

Coordinated activity across networks of neurons is a hallmark of both resting and active behavioural states in many species1-5. These global patterns alter energy metabolism over seconds to hours, which underpins the widespread use of oxygen consumption and glucose uptake as proxies of neural activity6,7. However, whether changes in neural activity are causally related to metabolic flux in intact circuits on the timescales associated with behaviour is unclear. Here we combine two-photon microscopy of the fly brain with sensors that enable the simultaneous measurement of neural activity and metabolic flux, across both resting and active behavioural states. We demonstrate that neural activity drives changes in metabolic flux, creating a tight coupling between these signals that can be measured across brain networks. Using local optogenetic perturbation, we demonstrate that even transient increases in neural activity result in rapid and persistent increases in cytosolic ATP, which suggests that neuronal metabolism predictively allocates resources to anticipate the energy demands of future activity. Finally, our studies reveal that the initiation of even minimal behavioural movements causes large-scale changes in the pattern of neural activity and energy metabolism, which reveals a widespread engagement of the brain. As the relationship between neural activity and energy metabolism is probably evolutionarily ancient and highly conserved, our studies provide a critical foundation for using metabolic proxies to capture changes in neural activity.


Assuntos
Comportamento Animal , Encéfalo/citologia , Encéfalo/fisiologia , Drosophila melanogaster/metabolismo , Drosophila melanogaster/fisiologia , Redes e Vias Metabólicas , Neurônios/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Encéfalo/metabolismo , Drosophila melanogaster/citologia , Metabolismo Energético , Feminino , Masculino , Vias Neurais , Optogenética , Descanso
16.
Int J Mol Sci ; 22(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33921053

RESUMO

Tetracycline antibiotics act by inhibiting bacterial protein translation. Given the bacterial ancestry of mitochondria, we tested the hypothesis that doxycycline-which belongs to the tetracycline class-reduces mitochondrial function, and results in cardiac contractile dysfunction in cultured H9C2 cardiomyoblasts, adult rat cardiomyocytes, in Drosophila and in mice. Ampicillin and carbenicillin were used as control antibiotics since these do not interfere with mitochondrial translation. In line with its specific inhibitory effect on mitochondrial translation, doxycycline caused a mitonuclear protein imbalance in doxycycline-treated H9C2 cells, reduced maximal mitochondrial respiration, particularly with complex I substrates, and mitochondria appeared fragmented. Flux measurements using stable isotope tracers showed a shift away from OXPHOS towards glycolysis after doxycycline exposure. Cardiac contractility measurements in adult cardiomyocytes and Drosophila melanogaster hearts showed an increased diastolic calcium concentration, and a higher arrhythmicity index. Systolic and diastolic dysfunction were observed after exposure to doxycycline. Mice treated with doxycycline showed mitochondrial complex I dysfunction, reduced OXPHOS capacity and impaired diastolic function. Doxycycline exacerbated diastolic dysfunction and reduced ejection fraction in a diabetes mouse model vulnerable for metabolic derangements. We therefore conclude that doxycycline impairs mitochondrial function and causes cardiac dysfunction.


Assuntos
Antibacterianos/farmacologia , Doxiciclina/farmacologia , Mitocôndrias Cardíacas/metabolismo , Contração Miocárdica/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Citosol/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Diástole/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/fisiologia , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Proteínas Nucleares/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Ratos
17.
Molecules ; 26(7)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918492

RESUMO

PURPOSE: Alternative methods for the use of animals in research have gained increasing importance, due to assessments evaluating the real need for their use and the development of legislation that regulates the subject. The principle of the 3R's (replacement, reduction and refinement) has been an important reference, such that in vitro, ex vivo and cord replacement methods have achieved a prominent place in research. METHODS: Therefore, due to successful results from studies developed with these methods, the present study aimed to evaluate the myorelaxant effect of the Dysphania ambrosioides essential oil (EODa) using a Sus scrofa domesticus coronary artery model, and the toxicity of both the Dysphania ambrosioides essential oil and its major constituent, α-terpinene, against Drosophila melanogaster in toxicity and negative geotaxis assays. RESULTS: The EODa relaxed the smooth muscle of swine coronary arteries precontracted with K+ and 5-HT in assays using Sus scrofa domesticus coronary arteries. The toxicity results presented LC50 values of 1.546 mg/mL and 2.282 mg/mL for the EODa and α-terpinene, respectively, thus showing the EODa and α-terpinene presented toxicity to these dipterans, with the EODa being more toxic. CONCLUSIONS: Moreover, the results reveal the possibility of using the EODa in vascular disease studies since it promoted the relaxation of the Sus scrofa domesticus coronary smooth muscle.


Assuntos
Chenopodiaceae/química , Vasos Coronários/fisiologia , Drosophila melanogaster/fisiologia , Relaxamento Muscular/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/toxicidade , Testes de Toxicidade , Animais , Vasos Coronários/efeitos dos fármacos , Monoterpenos Cicloexânicos/farmacologia , Modelos Animais de Doenças , Drosophila melanogaster/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Compostos Fitoquímicos/análise , Serotonina/farmacologia , Suínos
18.
Cell Mol Life Sci ; 78(10): 4805-4819, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33837450

RESUMO

During courtship, multiple information sources are integrated in the brain to reach a final decision, i.e., whether or not to mate. The brain functions for this complex behavior can be investigated by genetically manipulating genes and neurons, and performing anatomical, physiological, and behavioral analyses. Drosophila is a powerful model experimental system for such studies, which need to be integrated from molecular and cellular levels to the behavioral level, and has enabled pioneering research to be conducted. In male flies, which exhibit a variety of characteristic sexual behaviors, we have accumulated knowledge of many genes and neural circuits that control sexual behaviors. On the other hand, despite the importance of the mechanisms of mating decision-making in females from an evolutionary perspective (such as sexual selection), research on the mechanisms that control sexual behavior in females has progressed somewhat slower. In this review, we focus on the pre-mating behavior of female Drosophila melanogaster, and introduce previous key findings on the neuronal and molecular mechanisms that integrate sensory information and selective expression of behaviors toward the courting male.


Assuntos
Drosophila melanogaster/fisiologia , Motivação/fisiologia , Neurônios/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Feminino , Humanos
19.
Elife ; 102021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739284

RESUMO

G4C2 repeat expansions within the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The repeats undergo repeat-associated non-ATG translation to generate toxic dipeptide repeat proteins. Here, we show that insulin/IGF signalling is reduced in fly models of C9orf72 repeat expansion using RNA sequencing of adult brain. We further demonstrate that activation of insulin/IGF signalling can mitigate multiple neurodegenerative phenotypes in flies expressing either expanded G4C2 repeats or the toxic dipeptide repeat protein poly-GR. Levels of poly-GR are reduced when components of the insulin/IGF signalling pathway are genetically activated in the diseased flies, suggesting a mechanism of rescue. Modulating insulin signalling in mammalian cells also lowers poly-GR levels. Remarkably, systemic injection of insulin improves the survival of flies expressing G4C2 repeats. Overall, our data suggest that modulation of insulin/IGF signalling could be an effective therapeutic approach against C9orf72 ALS/FTD.


Assuntos
Esclerose Amiotrófica Lateral/genética , Proteína C9orf72/toxicidade , Expansão das Repetições de DNA , Drosophila melanogaster/fisiologia , Demência Frontotemporal/genética , Insulina/fisiologia , Transdução de Sinais , Animais , Proteína C9orf72/genética , Feminino
20.
Insect Biochem Mol Biol ; 133: 103569, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33753225

RESUMO

The fly genome contains a single ortholog of the evolutionarily conserved transcription factor hepatocyte nuclear factor 4 (HNF4), a broadly and constitutively expressed member of the nuclear receptor superfamily. Like its mammalian orthologs, Drosophila HNF4 (dHNF4) acts as a critical regulator of fatty acid and glucose homeostasis. Because of its role in energy storage and catabolism, the insect fat body controls non-autonomous organs including the ovaries, where lipid metabolism is essential for oogenesis. The present paper used dHNF4 overexpression (OE) in the fat bodies and ovaries to investigate its potential roles in lipid homeostasis and oogenesis. When the developing fat body overexpressed dHNF4, animals exhibited reduced size and failed to pupariate, but no changes in body composition were observed. Conditional OE of dHNF4 in the adult fat body produced a reduction in triacylglycerol content and reduced oogenesis. Ovary-specific dHNF4 OE increased oogenesis and egg-laying, but reduced the number of adult offspring. The phenotypic effects on oogenesis that arise upon dHNF4 OE in the fat body or ovary may be due to its function in controlling lipid utilization.


Assuntos
Drosophila melanogaster , Regulação da Expressão Gênica , Fator 4 Nuclear de Hepatócito , Metabolismo dos Lipídeos , Oogênese , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Drosophila melanogaster/fisiologia , Corpo Adiposo/metabolismo , Ácidos Graxos/metabolismo , Feminino , Fertilidade , Genes de Insetos , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Homeostase , Oogênese/genética , Oogênese/fisiologia , Ovário/metabolismo , Triglicerídeos/metabolismo
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