Fig. 12.

Systemic treatment with the ampakine CX546 increases BDNF mRNA content in rat and mouse hippocampus in vivo. A, B, Bar graphs show the densitometric quantification of BDNF cRNA labeling in hippocampal stratum granulosum (SG), CA3 stratum pyramidale, and CA1 stratum pyramidale of control (darkbars) and CX546-treated (lightbars) aged rats (A) and middle-aged mice (B). A, Data from one naive and three vehicle-control rats were combined for analysis, and aged rats were treated for 5 d with CX546 (30 mg/kg, i.p., once a day;n = 6) and killed 24 hr after the last injection. Error bars represent group mean values (± SD) for theSG and stratum pyramidale of fields CA3 and CA1. As shown, in vivo treatment with CX546 resulted in increased cRNA labeling in the granule cells as compared with control values (p < 0.03, Student'st test). No change was seen in the pyramidal cells.B, The bar graph shows BDNF cRNA hybridization levels in sections from control (naive and cyclodextrin vehicle;n = 6 total) middle-aged mice and middle-aged mice treated with CX546 (40 mg/kg, i.p.; n = 3) and killed 24 hr after injection. Error bars show group means (± SEM). Treatment with CX546 resulted in significantly elevated levels of BDNF cRNA labeling in the stratum granulosum (p = 0.036, Student's t test) and CA3 stratum pyramidale (p = 0.0025, Student's ttest) as compared with controls. As seen for the aged rat, there was no difference in hybridization within CA1 in the middle-aged mice.C, D, Dark-field photomicrographs show examples of BDNF cRNA hybridization in sections through the hippocampus from a control (naive) middle-aged mouse (C) and a middle-aged mouse killed 24 hr after a single injection of CX546 (40 mg/kg, i.p.;D). As shown in D, CX546 resulted in elevated BDNF cRNA labeling within the stratum granulosum (sg) and the CA3 stratum pyramidale (sp) that is restricted to the cell layers with no obvious change in hybridization within CA1. Scale bar, 200 μm.