PARTICULAR NUCLEAR TRANSCRIPTION FACTORS RESPONSIVE TO SYSTEMIC ADMINISTRATION OF KAINIC ACID IN MURINE BRAIN

Gel retardation electrophoresis revealed that binding of a radiolabele d double stranded oligonucleotide probe for the nuclear transcription factor activator protein-1 (AP1) was markedly potentiated 2 h after th e intraperitoneal injection of kainic acid (KA) at a dose range of 10- 40 mg/kg in a dose-dependent manner in the murine hippocampus. The pot entiation was seen in a manner independent of the crisis of convulsive seizures following the administration of KA at different doses. At th e highest dose employed, the systemic KA significantly potentiated the AP1 binding in most central discrete structures examined except the c erebellum. in contrast, KA significantly potentiated binding of a radi olabeled probe for cyclic AMP response element binding protein (CREB) in a dose-dependent fashion in the hippocampus, without altering that in other parts of murine brain. No significant alteration was detected in binding of a probe for c-Myc in any brain regions examined 2 h aft er the administration of KA at different doses. However, immunoblottin g analysis demonstrated that KA was ineffective in altering endogenous levels of both CREB and CREB phosphorlyated at serine(133) in the hip pocampus and cerebellum. These results suggest that in vivo systemic K A signals may be selectively transduced to nuclear AP1 in the hippocam pus through a mechanism different from phosphorylation of CREB at seri ne(133) in murine brain. Copyright (C) 1996 Elsevier Science Ltd.