A Study Of The Effects Of Dl-3-n-Butylphthalide On Drosophila Models Of Alzheimer's Disease

Objective Two types of drosophila overexpressingβ-amyloid were used to be models ofAlzheimer's disease(AD),which were fed with dl-3-n-Butylphthalide(NBP) until their death as a terminal.Life span,score of climbing behavior,and brain tissue ATP concentration of the flies were given the result to evaluate effects of NBP on AD's Drosophila.This study acquired some initial results of screening NBP to cure AD or not.Methods The wild-type flies,mild-type of AD flies and severe-type of AD flies were obtained by Gal4-UAS hybridization system.Each types of drosophila were randomly divided into solvent control,NBP0.3mmol/L,1.0mmol/L,3.0mmol/L, 10mmol/L groups respectively.They were fed on standard fly food with a streak of yeast that contain the required concentration of drug or solvent from 6 days old until their death without rest.every groups were performed under the same environmental conditions.The longevity assay per 3 days and 20 second climbing assay per 4 days were performed until flies' death or quantity not sufficient.On 17th day after flies born, the preparation of flies for brain ATP measuring were tested by Luciferin-Luciferase assay to quantification ATP content.In statistical methods,the survival time results were analyzed by Kruskal-Walli test.Outcomes of behavioral experiment were used of two-factor repeated measuring analysis of variance to evaluation,and paired comparison at the same time were evaluated by LSD test.ATP concentration results were changed by Logarithmically transformed first,then compared by SNK test.Statistical significance was accepted at P＜0.05. difference(P=0.922,P=0.186).In behavioral experiments,the effect on groups and time both showed statistically significant(P＜0.01,P＜0.01)in wild-type flies.Meanwhile, interaction effects between time and groups were also statistically significant(P＜0.01). NBP that act on mild-type AD flies showed that effects of group factor and time factor displayed statistically significant(P=0.011,P＜0.01),but the interaction between group and time did not show statistically significant(P=0.09).In severe-type of AD,the time factor showed statistically significant only(P＜0.01).Paired comparison at the same day showed that the climbing activity could be proved by giving some certain NBP in three types of flies.ATP concentration of mild AD flies' brain in NBP3.0mM group was found significant different than the solvent group(P=0.031).The results of ATP content in control flies were showed that the Solvent group's content was higher than drug groups(P>0.05).In severe AD flies,only the NBP10mmol/L group had the trend to be more than control but statistical analysis of results suggested meaningless(P＞0.05). Conclusions NBP could make the climbing activity of aging fruit flies including control and mild AD groups better,increasing ATP content of the mild AD flies' brain in certain concentration.In general,NBP has some protective effects on mild AD fruit flies, however,it showed some uncertainty effects in severe AD flies.