IMMEDIATE-EARLY GENE-EXPRESSION AND DELAYED CELL-DEATH IN LIMBIC AREAS OF THE RAT-BRAIN AFTER KAINIC ACID TREATMENT AND RECOVERY IN THE COLD

Systemic injection of kainic acid (KA) results in characteristic behav iors and programmed cell death in some regions of the rat brain. We us ed KA followed by recovery at 4 degrees C to restrict damage to limbic structures and compared patterns of immediate early gene (IEG) expres sion and associated DNA binding activity in these damaged areas with t hat in spared brain regions. Male Wistar rats were injected with BA (1 2 mg/kg, ip) and kept at 4 degrees C for 5 h. This treatment reduced t he severity of behaviors and restricted damage (observed by Nissl stai ning) to the CA1 and CA3 regions of the hippocampus and an area includ ing the entorhinal cortex. DNA laddering, characteristic of apoptosis, was first evident in the hippocampus and the entorhinal cortex 18 and 22 h after RA, respectively. The pattern of IEG mRNA induction fell i nto three classes: IEGs that were induced in both damaged and spared a reas (c-fos, fos B, jun B, and egr-1), IEGs that were induced specific ally in the damaged areas (fra-2 and c-jun), and an IEG that was signi ficantly induced by saline injection and/or the cold treatment (jun D) . The pattern of immunoreactivity closely followed that of mRNA expres sion. Binding to the AP-1 and EGR DNA consensus sequences increased in all three regions studied. This study describes a unique modification of the animal model of ICA-induced neurotoxicity which may prove a us eful tool for dissecting the molecular cascade that ultimately results in programmed cell death. (C) 1997 Academic Press.