The Effect Of Levetiracetam In Improving Alzheimer's Disease Phenotype In Aging Drosophila

Aging is a universal law in biological world. Aging represents the accumulation of damages in a human being over time, encompassing physical, psychological, and social changes. To uncover the aging mechanism it is essential for us to understand the principle of aging, make improvement in prevention and treatment of age-related diseases, and provide a theoretical rationale for anti-aging. Alzheimer's Disease(AD) plays a very important role in the aging process. Many studies have shown that neurodegenerative diseases are closely associated with aging, but its pathogenesis is still unknown. Animal models have evolutionary gene homology and functional similarity with human, and they are commonly used to study the pathogenesis and treatment methods in Alzheimer's disease research. Drosophila is an important model in studying complex biological process of cell biology and genetic pathways.Several techniques exist that give both temporal and spatial control over gene expression in Drosophila. Many of these approaches are derived from the widely used binary system GAL4-UAS (upstream activating sequence). We used a new kind of Drosophila with Gene-Switch GAL4 system. These Drosophila can express a secreted form of the human A?42 peptide, thus mimicking the extracellular distribution of the main pathogenic trigger in AD. We want to explore the therapeutic effect of drug Levetiracetam on AD, so we added different concentrations of the Levetiracetam into these flies'food. Then we checked the vacuoles and the deposition of amyloid-beta in AD Drosophila brains by frozen sections and Western-blot. We also used Q-PCR to observe the genes' expressions in flies'heads.(1) After several tests, we found that adding 12?M Levetiracetam can extend AD Drosophila lifespan and improve their locomotion ability, although it can not increase their fecundity.(2) Frozen sections of fly brains stained with hematoxylin and eosin showed that 12?M Levetiracetam can reduce the number of vacuoles in AD Drosophila, and Western-blot demonstrated that Levetiracetam can reduce A?42 peptides expression in brains.(3) The results of Q-PCR also showed that chronic treatment with this drug could significantly increase expressions of CG3168, glec, CG6218, CG33138 and CG10383.Overall, these studies establish a protective role for Levetiracetam against amyloid-? in Drosophila. Our findings support the treatment mechanism of Levetiracetam in AD, which the drug could regulate the development of CNS midline cells, energy metabolism pathway and carbohydrate metabolic pathway in Drosophila. Therefore, the study of Levetiracetam may be an important way to learn how to improve Alzheimer's Disease in human kind.