Figure 8

Aβ42 reduces levels of the transcription factor C-EBPα and IGF-1 reverses the reduction in levels of C-EBPα. (a,b) Treatment of organotypic slices with Aβ42 for 72 hours significantly decreases expression levels of the transcription factor C-EBPα in the cytosolic fraction. IGF-1 treatment increases basal levels of C-EBPα in the cytosol by ~1.6 fold and restores Aβ42-induced reduction in C-EBPα levels. (c,d) Treatment with Aβ42 for 72 hours significantly decreases levels of the C-EBPα in the nuclear fractions, suggesting that Aβ42 reduces the activation and nuclear translocation of C-EBPα. IGF-1 treatment increases the nuclear translocation of C-EBPα by ~1.8 fold and reverses the attenuation induced by Aβ42 of nuclear levels of C-EBPα. (e) ChIP analysis demonstrates that treatment with IGF-1 results in an about 3.5-fold increase in C-EBPα binding to the leptin promoter region. Aβ42 treatment results in a pronounced attenuation of C-EBPα binding to the leptin promoter region. Concomitant treatment with IGF-1 completely reverses the effects of Aβ42 on C-EBPα binding to the leptin promoter and produces a 3-fold increase in binding compared to control. *p < 0.05, **p < 0.01, and ***p < 0.001 versus control; ^† p < 0.05, ^{† †}p < 0.01, and ^{† ††} p < 0.001 versus Aβ42.