Sequential alterations of [ 3H]rolipram and [ 3H]cyclic adenosine monophosphate binding in the gerbil brain following transient cerebral ischemia

Abstract

We examined the sequential alterations in the binding of selective cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE) and cAMP-dependent protein kinase (cAMP-DPK) in the gerbil brain following transient cerebral ischemia using in vitro quantitative autoradiography. [ 3H]Rolipram, a cAMP-PDE inhibitor, and [ 3H]cAMP were used to label cAMP-PDE and cAMP-DPK, respectively. Gerbils were subjected to 2-min or 6-min ischemia. Two-minute ischemia, which caused no morphological neuronal damage, produced no significant changes in either [ 3H]rolipram or [ 3H]cAMP binding throughout the recirculation period. The reduction of [ 3H]rolipram binding in the CA1 subfield of the hippocampus began 6 h after 6-min ischemia. Seventy percent of [ 3H]rolipram binding was preserved at 4 days, at which time almost all CA1 pyramidal cells had been destroyed. On the other hand, the reduction of [ 3H]cAMP-binding sites in the CA1 subfield began 1 day after 6-min ischemia. At 4 days, 47% of [ 3H]cAMP-binding sites in the CA1 subfield were preserved. Furthermore, we observed a transient reduction of [ 3H]cAMP binding in the dentate gyrus, which is resistant to ischemia, at 1 day and 4 days. These results indicate that marked alterations of cAMP-PDE and cAMP-DPK precede neuronal death in the hippocampal CA1 subfield, and the dentate gyrus also showed a transient alteration of cAMP-DPK.