Rapamycin increases autophagy in brains of PDAPP mice.

<p><b>a, f and h</b>, representative immunoblots of hippocampal lysates from control- and rapamycin-treated transgenic PDAPP mice and non-transgenic littermate controls. <b>b, g and i</b>, quantitative analyses. <b>a and b</b>, LC3-II levels are decreased in hippocampi of rapamycin-treated transgenic PDAPP mice (*, <i>P</i> = 0.0009), but not in hippocampi of rapamycin-treated non-transgenic littermates. <b>c and d</b>, representative epifluorescent (<b>c</b>, 200×) and higher-magnification confocal (<b>d</b>, 600×) images of hippocampal CA1 (<b>e</b>, green box, region of epifluorescent images; blue box, region of confocal images) in control- and rapamycin-fed transgenic PDAPP mice stained with an anti-LC3 antibody. An increase in LC3-immunoreactive puncta was observed in CA1 projections of transgenic PDAPP mice following rapamycin administration. <b>f and g</b>, levels of the autophagic substrate p62SQSTM are decreased (*, <i>P</i> = 0.0015) in hippocampi of rapamycin-treated PDAPP transgenic mice. <b>f</b>, representative Western blots; <b>g</b>, quantitative analyses of p62SQSTM levels. <b>h and i</b>, Levels of phosphorylated (activated) p70 were decreased in brains of rapamycin-treated PDAPP and non-transgenic mice (*, <i>P</i> = 0.001 and <i>P</i> = 0.04 respectively). Significance of differences between group means were determined using two-tailed unpaired Student's <i>t</i> test. Data are means ± SEM.