The role of transcription factors cyclic-AMP responsive element modulator (CREM) and inducible cyclic-AMP early repressor (ICER) in epileptogenesis.
Alterations in the brain that contribute to the development of epilepsy, also called epileptogenesis, are not well understood, which makes it difficult to develop strategies for preventing epilepsy. Here we have studied the role of the CRE binding transcription factors, cyclic-AMP responsive element modulator (CREM) and inducible cyclic-AMP early repressor (ICER), in the development of epilepsy following pilocarpine induced status epilepticus (SE) in mice. Following SE, ICER mRNA and protein are increased in neurons. The increase in ICER, however, is not necessary for neuronal injury following SE as pilocarpine treatment induces equivalent neuronal injury in pyramidal neurons of wild type and CREM/ICER null mice. Following SE, the CREM/ICER null mice develop a more severe epileptic phenotype experiencing approximately threefold more frequent spontaneous seizures. Together these data suggest that the increase in ICER mRNA following SE may have a role in suppressing the severity of epilepsy.
Porter
B E
BE
Department of Pediatrics, The Children' Hospital of Philadelphia at the University of Pennsylvania, 502C Abramson, 3516 Civic Center Boulevard, Philadelphia, PA 19104, USA. Porterb@email.chop.edu
Lund
I V
IV
Varodayan
F P
FP
Wallace
R W
RW
Blendy
J A
JA
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017966:Pyramidal Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012640:Seizures / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013226:Status Epilepticus / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics
C497411:Crem protein, mouse; C497412:Crem protein, rat; D012333:RNA, Messenger; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP