The effects of repeated minimal electroconvulsive shock exposure on levels of mRNA encoding fibroblast growth factor-2 and nerve growth factor in limbic regions

Abstract

Chronic, but not acute, exposure to minimal electroconvulsive shock (ECS) has been shown to decrease vulnerability to neuronal cell death, without itself causing neuronal damage. One potential mechanism for the neuroprotective effect of ECS is the increase in fibroblast growth factor-2 (FGF-2) which occurs after chronic, but not acute, ECS exposure. This raises the possibility that repeated seizures over a period of several days may alter the transcriptional regulation of FGF-2. To test this hypothesis, the present study compared the effect of acute (1 day) vs. chronic (7 days) ECS treatment on levels of mRNA for FGF-2 in rhinal and frontal cortices, hippocampus, and olfactory bulbs. In addition, mRNA for another prominent neurotrophic factor, nerve growth factor (NGF), was assayed concurrently. At 8 h after acute ECS, mRNA levels increased by 60% for FGF-2 and 136% for NGF in rhinal cortex, 32% for FGF-2 and 36% for NGF in frontal cortex, and by 13% for NGF in hippocampus. After 7 days of ECS treatment the respective increases were 72% and 80%, 53% and 38%, and 28%. No increases were observed in olfactory bulbs after either treatment regimen. The peak increases in FGF-2 mRNA were consistently greater after chronic treatment, but the differences from those seen acutely reached significance in frontal cortex only. However, the duration over which mRNA for FGF-2 was elevated did not differ between the acute and chronic ECS groups. NGF mRNA induction was neither enhanced nor prolonged as a result of chronic ECS as compared to acute ECS treatment. These results suggest that chronic ECS treatment may lead to an enhanced rate of transcription of message for FGF-2 but not for NGF, in selected brain regions. At the same time, the results indicate that chronic ECS treatment induces FGF-2 and NGF mRNA expression in a tissue-specific manner and that this induction is maintained over the 7-day treatment period. The sustained increases in mRNAs for these trophic factors may contribute to the neuroprotective actions of chronic ECS treatment.