Functional significance of stimulatory GTP‐binding protein in hippocampus is associated with kindling‐elicited epileptogenesis

Abstract

In order to evaluate the involvement of the stimulatory G-protein (G s )-related transduction system in the basic mechanisms of epilepsy, we examine the expression levels of G sa mRNA and specific GTP-binding ability in the hippocampus of amygdaloid-kindled rats at various seizure stages. Northern blot analysis showed a significant increase in the G sa mRNA expression level in the bilateral hippocampus at 24 h after the last generalized seizure. The [ 3 H]-GTP-binding assay with isoproterenol (IPN), a b-receptor agonist, revealed a remarkable increase of B max values in the sham-operated control and partially kindled groups. However, the IPN-induced increase of B max values was abolished on both sides of the hippocampus at 24 h after and at 4 weeks after the last generalized seizure in fully kindled rats. These data suggest that alteration in the G s function and b-adrenergic receptor-G s coupling might be implicated in the neurobiological basis of the induction mechanisms of the generalization of seizures and the mechanisms of the maintenance of enduring epileptogenesis. Conversely, the G s -related transduction system might have a lesser impact on the acquisition process of epileptogenesis.

A Drosophila systems model of withdrawal from chronic pentylenetetrazole relevant in post-epileptogenesis

“…Transcriptomic characterization suggests altered expression of genes related to transcription regulator and GTPase regulator activities as causally associated with the fly model. Importantly, transcriptomic analysis of post-epileptogenesis rodent models has previously reported altered expression of genes related to these activities [21][22][23][24][25]. Given the transcriptomic similarity of previously described chronic PTZ Drosophila model with epileptogenesis [11], similarity of the present post-PTZ withdrawal part of the model with post-epileptogenesis is striking.…”

“…Overall, post-PTZ withdrawal regime was characterized by upregulation of genes overrepresenting transcription regulatory (Figure 3) and GTPase regulator activities, and downregulation of genes enriched in protein binding, oxidoreductase and electron carrier activities. It was interesting to note here the already existing gene expression evidence for upregulated Gprotein signaling and transcriptional regulation activities during post-epileptogenesis in rodent models [21][22][23][24].…”