Abstract

Intense activation of neurons triggers the appearance of immediate expression genes, including c-Fos. This gene is related to various signal cascades involved in biochemical processes such as neuronal plasticity, cell growth and mitosis. Here we investigate the expression pattern and the refractory period of c-Fos in rats and monkey’s brains after stimulation with pentylenetetrazol. Rats and monkeys were sacrificed at various times after PTZ-induced seizure. Here we show that rats and monkeys already showed c-Fos expression at 0.5 h after seizure. Yet, the pattern of protein expression was longer in monkeys than rats, and also was not uniform (relative intensity) across different brain regions in monkeys as opposed to rats. In addition monkeys had a regional brain variation with regard to the temporal profile of c-Fos expression, which was not seen in rats. The refractory period after a second PTZ stimulation was also markedly different between rats and monkeys with the latter even showing a summatory effect on c-Fos expression after a second stimulation. However, assessment of c-Fos mRNA in rats indicated a post-transcriptional control mechanism underlying the duration of the refractory period. The difference in the protein expression pattern in rodents and primates characterizes a functional aspect of brain biochemistry that differs between these mammalian orders and may contribute for the more developed primate cognitive complexity as compared to rodents given c-Fos involvement in cognitive and learning tasks.

Highlights

  • At the basic functional level, neurons, regardless of whether in rodents or primates show a remarkable similarity in their biochemical and biophysical characteristics

  • Preliminary evidence from our laboratory indicated that the temporal expression patterns of c-Fos after similar seizure events differed between rats and marmosets

  • Maximum expression levels were observed at 1 and 2 h after seizure induction, returning to baseline values at 6 h. This same expression pattern was observed in all of the 3 brain regions assessed (Figures 1A, 2). c-Fos mRNA levels were at the maximum expression level 30 min after seizures, and had returned to baseline values after 3 h

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Summary

Introduction

At the basic functional level, neurons, regardless of whether in rodents or primates show a remarkable similarity in their biochemical and biophysical characteristics. Broad differences at the biochemical level that could have wide implications for the understanding of different brain functioning between rodents and primates have not been reported, with the exception of those related to specific neuronal systems (e.g., visual and olfactory). One of such fundamental biochemical elements is the protooncogene c-Fos which encodes a nuclear phosphoprotein Fos, that forms a dimeric complex with another protein named Jun, that exhibits a DNA sequence binding sites for the transcription factor activator protein-1 (AP-1). This paper aims to draw a profile of expression of c-Fos by stimulation with PTZ in rats and monkeys in various regions of the central nervous system in order to test the possible differences that may exist between these two species

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