Blockade of Lysosomal Acid Ceramidase Induces GluN2B-Dependent Tau Phosphorylation in Rat Hippocampal Slices
Figure 1
Effects of d-NMAPPD on PPF and AMPA- and NMDA-mediated components of synaptic transmission. Hippocampal slices were maintained in normal aCSF containing 25 μM d-NMAPPD for at least 3 h prior to and during recording. (a) PPF of fEPSPs was measured at numerous interpulse intervals ranging from 50 to 400 ms in control and d-NMAPPD-treated slices. Representative traces are shown for the 50 ms interpulse interval. Data were determined by comparing the peak amplitude of the second relative with the first fEPSP (fEPSP2/fEPSP1100) and are means ± SEM obtained from 8 different rats (3 measurements per slice). (b) Graph illustrating AMPA-mediated components of synaptic transmission recorded at different stimulus intensities (50 to 400 μA) in a normal aCSF. Representative traces are shown for the 100, 250, and 400 μA stimulus intensities. Data on the amplitude of fEPSPs recorded in control slices and slices preexposed to d-NMAPPD (3 h) are presented in the bar graph (means ± SEM of 3 measurements per slice) obtained from 8 different rats. No statistical differences were observed between d-NMAPPD versus control slices (-test). (c) As in B, but NMDA-mediated components were pharmacologically isolated in a modified aCSF containing a low-magnesium concentration as well as antagonists for both AMPA and GABAA receptors (see Methods). In these conditions, Schaffer-commissural fibers were also cut between areas CA1 and CA3 sectors to reduce spiking in pyramidal cells. Data relative to NMDA-mediated components of synaptic transmission recorded in control slices and slices preexposed to d-NMAPPD (3 h) are presented in the bar graph (means ± SEM of 3 measurements per slice) obtained from 8 different rats. , , d-NMAPPD versus control values (-test). (d) Summary data on the amplitude of fEPSPs recorded at a stimulus intensity of 250 μA are expressed in percentage of control values and presented in the bar graph (means ± SEM of 3 measurements) obtained from 8 different rats. Note the ability of d-NMAPPD to enhance specifically the NMDA-mediated component of synaptic transmission. , d-NMAPPD versus control (-test).
