Fig. 3

Amyloid β secretion and synaptic transmission upon γ- and α-secretase inhibition. Primary rat neurons were treated with 0, 0.04, 0.3, and 3 μM γ-secretase inhibitor LY411575 or ADAM10 inhibitor GI254023X for 4 days. Secreted Aβ40 and Aβ42 to the cell-conditioned media were measured using immunochemilumisence techniques. Synaptic transmission was measured using an optical electrophysiology platform. a All three concentrations decrease secretion of Aβ40 (I) into cell culture media with approximately 80%. All three concentrations tended to decrease secretion of Aβ42 with approximately 40% (II), although not reaching statistical significance. Synaptic transmission (III) was significantly decreased when cells were exposed to 0.3 μM LY411575, and the transmission was further decreased at 3 μM. b GI254023X did not affect secretion of Aβ40 (I) or Aβ42 (II), nor did it have any effect on synaptic transmission (III). Bars represent mean +/− SEM. n = 3 from 3 individual primary cortical cultures for secretion data, n = 12 separate experiments from 2 individual primary cortical cultures for synaptic transmission data. Student’s t test is performed between the controls and each concentration. *p ≤ 0.05, ***p ≤ 0.001, ****p ≤ 0.0001