HYPOGLYCEMIA-INDUCED SEIZURES REDUCE CYCLIC-AMP RESPONSE ELEMENT-BINDING PROTEIN-LEVELS IN THE RAT HIPPOCAMPUS

Cyclic AMP response element binding protein (CREB) is a transcription factor that has been implicated in the activation of protein synthesis required for long-term memory. Since memory deficits are manifest fol lowing seizure, we undertook the present study to investigate the effe cts of hypoglycemia-induced seizure on CREB-immunoreactive neurons in several brain regions. We induced generalized seizures in male Long-Ev ans rats (n=5) by injecting them with insulin (30 IU/kg, i.p). Animals were recovered by administration of 3 ml of 30% glucose within 5 min of the occurrence of seizure. Control animals (n=3) were injected with saline instead of insulin. All animals were perfused 90 min after rec overy and the brains processed for CREB immunohistochemistry. Cell cou nts were determined for CREB-positive neurons using a computer-assiste d program. When compared to control animals there was a 50% decrease ( P<0.0001) in CREB-positive neurons in the CAI region of the experiment al animals. In the CA3 and dentate gyrus there was a 36% (P<0.001) and 25% decrease (P<0.001), respectively. Given the importance of hippoca mpus in memory-related processes and evidence that CREB is critical fo r memory formation, it is possible that seizures interfere with memory by disrupting CREB-dependent transcription. (C) 1998 IBRO. Published by Elsevier Science Ltd.