The neuroprotective effect of FTY720-P require ERK1/2 signaling.
(A) Fluorescent microscopic images of mouse primary cortical neuron cultures. ERK1/2 inhibitor U0126 almost completely suppressed FTY720-P–mediated protection against oAβ-induced neurotoxicity. Neurons were stained with anti–MAP-2 antibodies (green) and Aβ was stained with 4G8 antibodies (red). Scale bar: 50 µm. (B) Relative neuronal survival. The number of viable neurons (MAP-2–positive neurons) was quantified relative to results observed in untreated neurons. ERK1/2 inhibition almost completely ablated the neuroprotective effects of FTY720-P. oA 5 µM oAβ1-42treatment; FTY720-P, 100 pM FTY720-P treatment. *, P<0.001; †, P<0.001; ‡, P<0.001. Values are means ± SEM (n = 3). (C) WST-8 assay. Blocking ERK1/2 almost completely canceled the neuroprotective effects of FTY720-P, whereas it did not enhance oAβ–mediated neurotoxicity. oA 5 µM oAβ1-42 treatment; FTY720-P, 100 pM FTY720-P treatment. *, P<0.001; †, P<0.001; ‡, P<0.001. Values are means ± SEM (n = 6).