Figure 6.

Spaced ampakine treatments sustain elevated BDNF protein content without down-regulating AMPAR expression. A and B) As schematized in A, hippocampal slices were treated with CX614 for varied intervals (1 – 6 hr) and harvested 24 h after treatment onset. B) Bar graphs show group mean ± S.E.M. in situ hybridization labeling densities for GluR1 mRNA in str. granulosum and CA1 str. pyramidale. With CX614 at 50 μM (light bars), labeling was unaffected through 3 h but was lower than control values after 5 h treatments (*p < 0.05, **p < 0.01, ***p < 0.001 vs. con, SNK). CX614 at 25 μM (dark bars) did not affect GluR1 mRNA levels. C–E) As schematized in C, slices were treated with 50 μM CX614 for 3 h on four successive days; slices were collected daily (i) at the end of treatment for GluR1 mRNA analysis (D) or (ii) at the end of the 24 h period for ELISA measures of BDNF protein (E). D) Bar graph shows that GluR1 mRNA levels in str. granulosum (SG) remained at control values through treatment day 4. E) Plot of protein measures shows that total slice BDNF protein content was elevated at the end of the first day of treatment and remained elevated through treatment day 4 (**p < 0.01 vs. Con group, SNK) whereas GluR2 protein levels were unchanged throughout treatment. Mean ± S.E.M. values shown for n ≥ 8/group.