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

Mai Fathy, Mohamed Shahen, Samar El Kholy.




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.

Key words: Parkinson disease, Rotenone, Drosophila, metabolism, modeling.






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