Beta amyloid （Aβ42）-induced dysfunction and loss of synapses are believed to be major underlying mechanisms for the progressive loss of learning and memory abilities in Alzheimer＇s disease （AD）. The vast majority of investigations on AD-related synaptic impairment focus on synaptic plasticity, especially the decline of long-term potentiation of synaptic transmission caused by extracellular Aβ42. Changes in other aspects of synaptic and neuronal functions are less studied or undiscovered. Here, we report that intraneuronal accumulation of Aβ42 induced an age- dependent slowing of neuronal transmission along pathways involving multiple synapses.
The negative-geotaxis climbing assay is used to efficiently study aging and neurodegeneration in Drosophila.To make it suitable for large-scale study,a method called the rapid iterative negative geotaxis（RING） assay has been established by simultaneously photographing the climbing of multiple groups of flies when they are manually tapped down in test tubes.Here,we automated the assay by using a well-controlled electric motor to drive the tapping,and a homemade program to analyze the climbing height of flies.Using the automated RING（aRING） assay,we found that the climbing ability of a strain of wild-type flies,males in particular,declined rapidly before day 21 after eclosion,but slowly from day 21 to 35.We also found that the expression of arctic mutant Aβ_（42） accelerated the age-dependent decline in the climbing ability of flies.Moreover,using aRING,we examined the effect of third chromosome deficiencies on the accelerated locomotor decline in Aβ_（42）-expressing flies,and isolated 7 suppressors and15 enhancers.
Stroke is a leading cause of death worldwide. Up to one thousand potential drugs or interventions have been developed to treat stroke, out of which;60 have gone on to clinical trials. However, none of them has been successful. New insights into the molecular and cellular mechanisms of ischemia-induced injury are needed for discovering new therapeutic targets. Recently, Drosophila has been used to uncover new hypoxia-related genes. In this study, we describe an efficient and reliable assay with a sophisticated apparatus for studying the effects of oxygen deprivation on flies. Using this assay, wild-type flies were exposed to an anoxic environment for varying lengths of time, then the cumulative death rate and mobility recovery were systematically analyzed. We found that anoxia for over one hour caused lethality. The cumulative death rate on day 5 after anoxia was linearly and positively correlatedwith the duration of anoxia, and reached 50% when the duration was 2.5 h–3 h. We also found that the mobility recovery in normoxia was slow, as the climbing ability remained largely unchanged 4 h–6 h after 2.5-h of anoxia.We suggest that 2.5 h–3 h of anoxia and 4 h–6 h of recovery before mobility analysis are appropriate for future use of the anoxia assay.
