scholarly journals G-protein αq gene expression plays a role in alcohol tolerance in Drosophila melanogaster

2019 ◽  
Vol 3 ◽  
pp. 239821281988308
Author(s):  
Benjamin Aleyakpo ◽  
Oghenetega Umukoro ◽  
Ryan Kavlie ◽  
Daniel C. Ranson ◽  
Andrew Thompsett ◽  
...  

Ethanol is a psychoactive substance causing both short- and long-term behavioural changes in humans and animal models. We have used the fruit fly Drosophila melanogaster to investigate the effect of ethanol exposure on the expression of the Gαq protein subunit. Repetitive exposure to ethanol causes a reduction in sensitivity (tolerance) to ethanol, which we have measured as the time for 50% of a set of flies to become sedated after exposure to ethanol (ST50). We demonstrate that the same treatment that induces an increase in ST50 over consecutive days (tolerance) also causes a decrease in Gαq protein subunit expression at both the messenger RNA and protein level. To identify whether there may be a causal relationship between these two outcomes, we have developed strains of flies in which Gαq messenger RNA expression is suppressed in a time- and tissue-specific manner. In these flies, the sensitivity to ethanol and the development of tolerance are altered. This work further supports the value of Drosophila as a model to dissect the molecular mechanisms of the behavioural response to alcohol and identifies G proteins as potentially important regulatory targets for alcohol use disorders.

2009 ◽  
Vol 107 (6) ◽  
pp. 1771-1780 ◽  
Author(s):  
Jens Bangsbo ◽  
Thomas P. Gunnarsson ◽  
Jesper Wendell ◽  
Lars Nybo ◽  
Martin Thomassen

The present study examined muscle adaptations and alterations in work capacity in endurance-trained runners as a result of a reduced amount of training combined with speed endurance training. For a 6- to 9-wk period, 17 runners were assigned to either a speed endurance group with a 25% reduction in the amount of training but including speed endurance training consisting of six to twelve 30-s sprint runs 3–4 times/wk (SET group n = 12) or a control group ( n = 5), which continued the endurance training (∼55 km/wk). For the SET group, the expression of the muscle Na+-K+pump α2-subunit was 68% higher ( P < 0.05) and the plasma K+level was reduced ( P < 0.05) during repeated intense running after 9 wk. Performance in a 30-s sprint test and the first of the supramaximal exhaustive runs was improved ( P < 0.05) by 7% and 36%, respectively, after the speed endurance training period. In the SET group, maximal O2uptake was unaltered, but the 3-km (3,000-m) time was reduced ( P < 0.05) from 10.4 ± 0.1 to 10.1 ± 0.1 min and the 10-km (10,000-m) time was improved from 37.3 ± 0.4 to 36.3 ± 0.4 min (means ± SE). Muscle protein expression and performance remained unaltered in the control group. The present data suggest that both short- and long-term exercise performances can be improved with a reduction in training volume if speed endurance training is performed and that the Na+-K+pump plays a role in the control of K+homeostasis and in the development of fatigue during repeated high-intensity exercise.


2012 ◽  
Vol 8 (6) ◽  
pp. 1050-1054 ◽  
Author(s):  
H. Colinet ◽  
D. Renault

Immobilization of insects is necessary for various experimental purposes, and CO 2 exposure remains the most popular anaesthetic method in entomological research. A number of negative side effects of CO 2 anaesthesia have been reported, but CO 2 probably brings about metabolic modifications that are poorly known. In this work, we used GC/MS-based metabolic fingerprinting to assess the effect of CO 2 anaesthesia in Drosophila melanogaster adults. We analysed metabolic variation of flies submitted to acute CO 2 exposure and assessed the temporal metabolic changes during short- and long-term recovery. We found that D. melanogaster metabotypes were significantly affected by the anaesthetic treatment. Metabolic changes caused by acute CO 2 exposure were still manifested after 14 h of recovery. However, we found no evidence of metabolic alterations when a long recovery period was allowed (more than 24 h). This study points to some metabolic pathways altered during CO 2 anaesthesia (e.g. energetic metabolism). Evidence of short-term metabolic changes indicates that CO 2 anaesthesia should be used with utmost caution in physiological studies when a short recovery is allowed. In spite of this, CO 2 treatment seems to be an acceptable anaesthetic method provided that a long recovery period is allowed (more than 24 h).


2007 ◽  
Vol 293 (5) ◽  
pp. R1997-R2005 ◽  
Author(s):  
Charles A. Ducsay ◽  
Kim Hyatt ◽  
Malgorzata Mlynarczyk ◽  
Brandon K. Root ◽  
Kanchan M. Kaushal ◽  
...  

We previously communicated that long-term hypoxia (LTH) resulted in a selective reduction in plasma epinephrine following acute stress in fetal sheep. The present study tested the hypothesis that LTH selectively reduces adrenomedullary expression of phenylethanolamine-N-methyltransferase (PNMT), the rate-limiting enzyme for epinephrine synthesis. We also examined the effect of LTH on adrenomedullary nicotinic, muscarinic, and glucocorticoid receptor (GR) expression. Ewes were maintained at high altitude (3,820 m) from 30 to 138 days gestation (dGA); adrenomedullary tissue was collected from LTH and age-matched, normoxic control fetuses at 139–141 dGA. Contrary to our hypothesis, in addition to PNMT, adrenomedullary expression (mRNA, protein) of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) were reduced in the LTH fetus. Immunocytochemistry indicated that TH and DBH expression was lower throughout the medulla, while PNMT appeared to reflect a reduction in PNMT-expressing cells. Nicotinic receptor alpha 1, 2, 3, 5, 6, 7, beta 1, 2, and 4 subunits were expressed in the medulla of LTH and control fetuses. Messenger RNA for alpha 1 and 7 and beta 1 and 2 subunits was lower in LTH fetuses. Muscarinic receptors M1, M2, and M3 as well as the GR were also expressed, and no differences were noted between groups. In summary, LTH in fetal sheep has a profound effect on expression of key enzymes mediating adrenomedullary catecholamine synthesis. Further, LTH impacts nicotinic receptor subunit expression potentially altering cholinergic neurotransmission within the medulla. These findings have important implications regarding fetal cardiovascular and metabolic responses to stress in the LTH fetus.


Author(s):  
Srdan Verstovsek

Overview: The discovery that a somatic point mutation (JAK2V617F) in the Janus kinase 2 ( JAK2) is highly prevalent in patients with myeloproliferative neoplasms (MPNs) has been a crucial breakthrough in our understanding of the underlying molecular mechanisms of these diseases. Therefore, preclinical and clinical research in recent years has focused intensely on the development of new therapies targeted to JAK2. These efforts culminated in recent approval of ruxolitinib as the first official therapy for patients with intermediate- or high-risk myelofibrosis (MF). Therapy with JAK2 inhibitors substantially improves quality of life and reduces organomegaly in MF with or without JAKV617F mutation. Recent results suggest that patients with advanced MF may live longer when receiving therapy with ruxolitinib. However, JAK2 inhibitors do not eliminate the disease and new medications are needed to expand on the benefits seen with JAK2 inhibitors. Although many agents are still in the early stages of development, the wealth of publications and presentations has continued to support our growing understanding of the pathophysiology of MF as well as the potential short- and long-term outcomes of these new and diverse approaches to treatment. Focus of ongoing efforts is particularly on the improvements in anemia and fibrosis, as well as on rational combination trials of JAK2 inhibitors and other potentially active agents. Therapeutic potential and limitations of JAK2 inhibitors and other novel medications in clinical studies are reviewed.


Cholesterol ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Ryusuke Niwa ◽  
Yuko S. Niwa

Cholesterol has long been recognized for its versatile roles in influencing the biophysical properties of cell membranes and for serving as a precursor of steroid hormones. While many aspects of cholesterol biosynthesis are well understood, little is currently known about the molecular mechanisms of cholesterol metabolism and homeostasis. Recently, genetic approaches in the fruit fly, Drosophila melanogaster, have been successfully used for the analysis of molecular mechanisms that regulate cholesterol metabolism and homeostasis. This paper summarizes the recent studies on genes that regulate cholesterol metabolism and homeostasis, including neverland, Niemann Pick type C(NPC) disease genes, and DHR96.


2016 ◽  
Vol 113 (17) ◽  
pp. 4818-4823 ◽  
Author(s):  
Séverine Trannoy ◽  
Jill Penn ◽  
Kenia Lucey ◽  
David Popovic ◽  
Edward A. Kravitz

In many animal species, learning and memory have been found to play important roles in regulating intra- and interspecific behavioral interactions in varying environments. In such contexts, aggression is commonly used to obtain desired resources. Previous defeats or victories during aggressive interactions have been shown to influence the outcome of later contests, revealing loser and winner effects. In this study, we asked whether short- and/or long-term behavioral consequences accompany victories and defeats in dyadic pairings between male Drosophila melanogaster and how long those effects remain. The results demonstrated that single fights induced important behavioral changes in both combatants and resulted in the formation of short-term loser and winner effects. These decayed over several hours, with the duration depending on the level of familiarity of the opponents. Repeated defeats induced a long-lasting loser effect that was dependent on de novo protein synthesis, whereas repeated victories had no long-term behavioral consequences. This suggests that separate mechanisms govern the formation of loser and winner effects. These studies aim to lay a foundation for future investigations exploring the molecular mechanisms and circuitry underlying the nervous system changes induced by winning and losing bouts during agonistic encounters.


2018 ◽  
Vol 6 (3) ◽  
pp. 17 ◽  
Author(s):  
Mireya Ruiz-Losada ◽  
David Blom-Dahl ◽  
Sergio Córdoba ◽  
Carlos Estella

Appendages are external projections of the body that serve the animal for locomotion, feeding, or environment exploration. The appendages of the fruit fly Drosophila melanogaster are derived from the imaginal discs, epithelial sac-like structures specified in the embryo that grow and pattern during larva development. In the last decades, genetic and developmental studies in the fruit fly have provided extensive knowledge regarding the mechanisms that direct the formation of the appendages. Importantly, many of the signaling pathways and patterning genes identified and characterized in Drosophila have similar functions during vertebrate appendage development. In this review, we will summarize the genetic and molecular mechanisms that lead to the specification of appendage primordia in the embryo and their posterior patterning during imaginal disc development. The identification of the regulatory logic underlying appendage specification in Drosophila suggests that the evolutionary origin of the insect wing is, in part, related to the development of ventral appendages.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Natalia El-Merhie ◽  
Arne Krüger ◽  
Karin Uliczka ◽  
Stephanie Papenmeier ◽  
Thomas Roeder ◽  
...  

AbstractE-cigarettes are heavily advertised as healthier alternative to common tobacco cigarettes, leading more and more women to switch from regular cigarettes to ENDS (electronic nicotine delivery system) during pregnancy. While the noxious consequences of tobacco smoking during pregnancy on the offspring health are well-described, information on the long-term consequences due to maternal use of e-cigarettes do not exist so far. Therefore, we aimed to investigate how maternal e-nicotine influences offspring development from earliest life until adulthood. To this end, virgin femaleDrosophila melanogasterflies were exposed to nicotine vapor (8 µg nicotine) once per hour for a total of eight times. Following the last exposure, e-nicotine or sham exposed females were mated with non-exposed males. The F1-generation was then analyzed for viability, growth and airway structure. We demonstrate that maternal exposure to e-nicotine not only leads to reduced maternal fertility, but also negatively affects size and weight, as well as tracheal development of the F1-generation, lasting from embryonic stage until adulthood. These results not only underline the need for studies investigating the effects of maternal vaping on offspring health, but also propose our established model for analyzing molecular mechanisms and signaling pathways mediating these intergenerational changes.


Author(s):  
Oluwatosin Imoleayo, Oyeniran

The rise in the cases of neurodegenerative diseases, such as the familial forms of Alzheimer’s disease is worrisome and a burden to many societies in our ever-increasing world. Due to the complexity in the nature of the brain and spinal cord characterized by an extremely organized network of neuronal cells, there is a need to answer scientific inquiries in uncomplicated, though similar, systems. Drosophila melanogaster (fruit-fly) is a well-studied and easily managed genetic model organism used for discerning the molecular mechanisms of many human diseases. There are strong conservations of several basic biological, physiological and neurological features between D. melanogaster and mammals, as about 75% of all human disease-causing genes are considered to possess a functional homolog in the fruit-fly. The development of Drosophila models of several neurodegenerative disorders via developed transgenic technologies has presented spectacular similarities to human diseases. An advantage that the fruit-fly has over other model organisms, such as the mouse, is its comparatively brief lifespan, which allows complex inquiries about brain functions to be addressed more quickly. Furthermore, there have been steady increases in understanding the pathophysiological basis of many neurological disorders via genetic screenings with the aid of Drosophila models. This review presents a widespread summary of the fruit-fly models relevant to Alzheimer’s disease, and highlight important genetic modifiers that have been recognized using this model.


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