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 following seizure, we undertook the present study to investigate the effects of hypoglycemia-induced seizure on CREB-immunoreactive neurons in several brain regions. We induced generalized seizures in male Long Evans 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 recovery and the brains processed for CREB immunohistochemistry. Cell counts were determined for CREB-positive neurons using a computer-assisted program. When compared to control animals there was a 50% decrease (P<0.0001) in CREB-positive neurons in the CA1 region of the experimental 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 hippocampus in memory-related processes and evidence that CREB is critical for memory formation, it is possible that seizures interfere with memory by disrupting CREB-dependent transcription.
Panickar
K S
KS
Department of Pharmacology, University of Florida, Gainesville 32610, USA.
Purushotham
K
K
King
M A
MA
Rajakumar
G
G
Simpkins
J W
JW
D000818:Animals; D001921:Brain / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007003:Hypoglycemia / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D012016:Reference Values; D012640:Seizures / Q000209:etiology / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D007328:Insulin