FOCAL BRAIN INJURY INDUCES MULTIPLE IMMEDIATE-EARLY GENES ENCODING ZINC-FINGER TRANSCRIPTION FACTORS

Focal brain injury is known to markedly induce the fos and jun families of immediate early genes (IEGs). This study employed in situ hybridization to examine the effects of focal brain injury, produced by the intracerebral injection of saline or ibotenic acid on the expression of IEGs encoding zinc finger transcription factors. Thirty minutes after the injections, NGFI-A, NGFI-B, NGFI-C, and egr-3 mRNAs were induced in dentate gyrus, hippocampal pyramidal cells, cerebral cortex, caudate-putamen and piriform cortex of the injured hemisphere. Nurr1 was induced in hippocampal pyramidal cells and dentate granule cells. After three hours the induction of NGFI-A, NGFI-B, NGFI-C and Nurr1 persisted in all brain regions except for the dentate granule cells. By six hours after injection mRNAs for most of the zinc finger genes had returned to control levels. However, the expression of egr-3 3 and 6 h after the injection was identical to that observed at 30 min after the injection and it was the only gene the expression of which persisted 6 h following the injections. Twenty-four hours after the injection, the expression of all five IEGs returned to control levels. In general, no gross differences in the IEG induction were observed between the animals injected with saline and ibotenic acid. Since these zinc finger genes were expressed in the same regions where fos and jun family members are induced by similar types of brain injury, it is suggested that these transcription factors may act in concert with Fos/Jun family members. These observations should be considered when studying the effect of invasive manipulations on IEG expression in the brain and add to the evidence for remote effects of focal brain injury.