Abstracts

RATIONALE: The basal forebrain cholinergic neurons, which are involved in the modulation of memory and susceptibility to seizures, heavily innervate the hippocampal formation and neocortex. However, it is still unclear whether seizures affect the cholinergic system. The goal of this study was to determine the effects of recurrent seizures in immature rats upon cholinergic innervation of the CA1 and CA3 regions of the hippocampus and dentate gyrus.
METHODS: Rat pups were submitted to recurrent seizures using flurothyl 5 times a day during 5 days from postnatal ages 0 (P0) to P4 and from P15 to P19, in a total of 25 seizures per rat. Age-matched controls were handled in a similar manner but not submitted to seizures. Animals from all age groups were sacrificed at P45. Brain tissue sections at the level of the dorsal hippocampus and basal forebrain were processed for acetylcholinesterase (AChE) histochemistry and choline acethyltransferase immunohistochemistry.
RESULTS: Rats submitted to seizures from both P0 to P4 and P15 to P19 showed significantly greater density AChE-labeled fibers in the molecular layer of the DG than controls. No significant differences in the density of AChE-labeled fibers were found in the stratum oriens of the CA1 and CA3 regions between rats submitted to seizures and controls from both age groups.
CONCLUSIONS: We found an increased density of AChE-labeled fibers in the molecular layer of the DG in rats that had a series of flurothyl-induced seizures during early postnatal period. It remains unknown whether the sprouting of cholinergic fibers in the DG that follows recurrent seizures in immature rats contributes to cognitive impairment or increased susceptibility to seizures.
[Supported by: This study was supported by a grant from NINDS to G.L.H. (NS27984).
Dr. Silveira was supported by a research fellowship from the Epilepsy Foundation of America.]