FIGURE 1:

Human Aβ42 causes progressive reduction of synapses in adult motor neurons and PI3K activation suppresses this effect with no transcriptional changes in core synaptic genes. (A) Representative confocal images of neuromuscular junctions (NMJs) of the ventral longitudinal muscle in the third abdominal segment of adult female at 15 d postexpression. Active zones monitored as nc82 immune-positive area. (B) Time course of synaptic effects. At 7, 15, and 25 d posttriggering genetic expression, the Aβ42 flies show a drastic reduction of synaptic area, while at 25 d most synapses have disappeared. Note that PI3K flies increase the synaptic signal along the three time points and the suppression effects on Aβ42 are still effective at 25 d. One-way ANOVA test with ***, p < 0.001. (C) RT-qPCR analysis of three genes encoding synapse proteins, bruchpilot, liprin, and synaptobrevin, carried out in 15-d-old adult female heads. Results of mRNA levels (Y axis) are represented as fold induction in triplicate experiments normalized with respect to the control genotype (see below). Histogram differences are not statistically significant (Student’s t test). Genotypes: Control (UAS-LacZ/elav^C155-Gal4; +/+; Tub-Gal80^TS/+), PI3K (UAS-PI3K^CAAX/elav^C155-Gal4; +/+; Tub-Gal80^TS/+), Aβ42 (elav^C155-Gal4/+; UAS-Aβ42(2x)/+; Tub-Gal80^TS/+), PI3K/Aβ42 (UAS-PI3K^CAAX/elav^C155-Gal4; UAS-Aβ42(2x)/+; Tub-Gal80^TS/+). Data represent mean ± SD. Data in B are processed by IMARIS Bitplane. Scale bar is 20 μm.