Genes controlling appetite, gut emptying rate and metabolism in the early stage of Rotenone-induced semi-Parkinsonism in Drosophila melanogaster

Mai Fathy, Mohamed Shaheen, S. Kholy
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Abstract

Parkinson’s disease (PD) is one of the most serious neurodegenerative diseases. PD is characterized by progressive death of dopamine producing cells in Substantia nigra pars compacta within human brain causing serious locomotor defects such as tremor as well as non-motor symptoms including metabolic deficiency and constipation. Despite the plethora of information regarding the underlying mechanisms related to locomotion impairment, signal pathways/genes involved in metabolic deficiency and constipation remain unclear. This study aims to explore the most important key genes involved in metabolic syndrome and constipation observed in PD patients. To achieve this goal, real-time polymerase chain reaction (RT PCR) of a group of genes supposed in previous findings to have a role in these syndromes in rotenone - induced PD Drosophila model was performed. One -day- old Canton S flies were fed on filter paper saturated with rotenone glucose solution(5mM rotenone in 10% glucose) at 25 ̊C for 24h.Thereafter, we focus on genes whose up-regulated expression level for all subsequent experiment. Next, metabolic parameters (total protein, lipid and carbohydrates), rate of food consumption and defecation in flies that’s knocking down in the corresponding genes were evaluated. Results revealed that feeding rate decreased when CG17544 and CG16848 genes were up-regulated; consequently those flies had reduced body weight. Meanwhile, knocking down CG16848 and CG12913. This study provide evidence that using the human homologues of these Drosophila genes for molecular docking of new pharmacotherapeutics may help to enhance the quality of life of PD patients through improving metabolism as well as defecation.
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鱼藤酮诱导的黑腹果蝇半帕金森病早期控制食欲、肠道排空率和代谢的基因
帕金森病(PD)是最严重的神经退行性疾病之一。PD的特点是人脑致密黑质产生多巴胺的细胞进行性死亡,导致严重的运动缺陷,如震颤,以及代谢不足和便秘等非运动症状。尽管关于运动障碍相关的潜在机制的信息过多,但代谢缺乏和便秘相关的信号通路/基因仍不清楚。本研究旨在探讨PD患者代谢综合征和便秘最重要的关键基因。为了实现这一目标,我们在鱼藤酮诱导的帕金森病果蝇模型中对一组先前研究中被认为在这些综合征中起作用的基因进行了实时聚合酶链反应(RT PCR)。取1日龄广东蝇,用鱼藤酮葡萄糖溶液(10%葡萄糖中含有5mM鱼藤酮)饱和滤纸在25℃下饲养24h。此后,我们在后续的所有实验中都将重点关注表达水平上调的基因。接下来,研究人员评估了果蝇的代谢参数(总蛋白质、脂质和碳水化合物)、食物消耗率和排便率,这些参数都在相应的基因中被敲除。结果表明,上调CG17544和CG16848基因,摄食率降低;因此,这些苍蝇的体重减轻了。同时击倒CG16848和CG12913。本研究为利用这些果蝇基因的人类同源物进行新药物治疗的分子对接提供了证据,可能有助于通过改善代谢和排便来提高PD患者的生活质量。
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