Rapamycin aggravates neurodegeneration in fly model of FXTAS.

<p>(<b>A</b>) (<b>i</b>) Rapamycin aggravates ommatidial degeneration of <i>GMR-GAL4>CGG₉₀</i> (4 days old after eclosion). <b>a–c</b> LM images, <b>d–f</b> SEM images. The concentrations of rapamycin are: 0 μM (<b>a, d</b>), 2.5 μM (<b>b, e</b>), 5 μM (<b>c, f</b>). (<b>ii</b>) Quantitative analyses of eye phenotypes of <i>GMR-GAL4>CGG₉₀</i> with administration of rapamycin (4 days old after eclosion). Data show mean phenotype score ± SEM (Mann-Whitney test, *** = p<0.0001). (<b>B</b>) Rapamycin shortens lifespan of <i>Daughterless-GAL4>CGG₉₀</i> (<b>i</b>) while it presents no effect in <i>Daughterless-GAL4>EGFP</i> (<b>ii</b>). The concentrations of rapamycin are: 0 μM, 2.5 μM, 5 μM. (<b>C</b>) (<b>i</b>) Rapamycin decreases locomotor activity of <i>NRV2-GAL4>CGG₉₀</i>. The concentrations of rapamycin are: 0 μM, 2.5 μM, 5 μM. (<b>ii</b>) Statistical analyses of locomotion of <i>NRV2-GAL4>CGG₉₀</i> with rapamycin treatment (10 days old after eclosion). Data show mean locomotor activity ± SEM (Student's t-test, ** = p<0.001). (<b>D</b>) (<b>i</b>) Locomotor activity of <i>NRV2-GAL4>EGFP</i> is not altered by rapamycin. The concentrations of rapamycin are: 0 μM, 2.5 μM, 5 μM. (<b>ii</b>) Statistical analyses of locomotion of <i>NRV2-GAL4>EGFP</i> with rapamycin treatment (10 days old after eclosion). Data show mean locomotor activity ± SEM (Student's t-test, ns). (<b>E</b>) High doses of rapamycin administrated from early adulthood shortens lifespan of <i>Daughterless-GAL4>CGG₉₀</i>. The concentrations of rapamycin are: 0 μM, 50 μM, 200 μM, 400 μM. (<b>F</b>) Total RNA was isolated from heads of <i>GMR-GAL4>CGG90</i> with rapamycin treatment. The concentrations of rapamycin (from column 1 to column 3) are: 0 μM, 2.5 μM, 5 μM. Rapamycin does not increase RNA levels. The mild decrease of RNA level with rapamycin treatment should be attribute to the ablation of translation by restraining phosphorylation of S6K and 4E-BP1.