Fig. 2.

ERK-dependent changes in Aβ metabolism. (A) Young PS1APP mice were administered vehicle (aCSF), a MEK inhibitor (PD98059, 100 μM), or an ERK inhibitor (FR180204, 100 μM) by reverse microdialysis (n = 6–8 per group). At 24 h from the beginning of treatment, the MEK and ERK inhibitors alone significantly increased ISF Aβ levels by 37.7 ± 3.9% (P = 0.001) and 39.4 ± 1.6% (P < 0.0001) compared with baseline levels. Coadministration of citalopram (10 mg/kg i.p.) with either of these inhibitors blocked the SSRI-dependent reduction in ISF Aβ. ISF Aβ levels were not significantly different between inhibitor-treated and inhibitor plus citalopram-treated mice. (B) Citalopram increased α-secretase enzymatic activity by 25 ± 4.9% (P = 0.01) within the hippocampus with no change in β-secretase activity (n = 8 per group). Data presented as mean ± SEM.