Fig. 3.

Chronic SSRI administration reduces plaque load in PS1APP transgenic mice. Beginning at 3 mo of age, PS1APP hemizygous mice were treated with water or citalopram (8 mg/kg/day) in drinking water for 4 mo (n = 10 per group). Representative images of cortex and hippocampus stained for Aβ plaques in (A) water and (B) citalopram-treated mice. (C) Quantification of plaque load in the hippocampus and cortex was performed blinded. Surface area covered by plaques was reduced in citalopram-treated mice to 57.9 ± 6.1% (P = 0.03) and 49.5 ± 6.2% (P = 0.004) of mean levels in water-treated mice. (D) Guanidine-extracted Aβ_x-40 and Aβ_x-42 in the hippocampus and cortex was significantly reduced in citalopram-treated mice. (E) Aβ_x-40 and Aβ_x-42 levels within the CSF of citalopram-treated mice were reduced to 71.4 ± 7.5% (P = 0.02) and 49.5 ± 6.2% (P < 0.0001) compared with mean levels in water-treated mice. (F) α-Secretase enzymatic activity was significantly increased in chronic citalopram mice (P < 0.001); however, β-secretase activity was unchanged. (G) Quantitative PCR showed that mRNA levels of ADAM10 did not change significantly but that memapsin-2 (P = 0.01) and two components of the γ-secretase complex, presenilin-1 and nicastrin, were significantly reduced in citalopram-treated mice (P = 0.02 and P = 0.01; n = 9–10 per group). APH-1B, neprilysin, and LRP1 mRNA levels did not change following citalopram treatment. Values normalized to mean level in water-treated mice. Data presented as mean ± SEM.