Συναπτική δράση παραγώγων νευροδιαβιβαστών και αντιεπιληπτικών φαρμάκων στον εγκέφαλο φυσιολογικών και επιληπτικών πειραματοζώων

The aim of the study presented here is to contribute to the investigation of epileptogenesis. The study is divided in three parts. The first part investigates possible mechanisms of inherited epileptogenesis in the epileptic mutant mouse tottering (tg/tg) by examining the following questions: 1) The function of cholinergic system in the cerebral cortex (through determination of the activity and kinetic properties of enzyme ChAT). 2) The physiological neuronal excitability and its changes due to: a) the increase (+2mM) of extracellular Κ⁺, b) the activation of NMDA receptors and c) the application of 10μΜ Adenosine (endogenous substance with antiepileptic properties). Epileptic mice (tg/tg) and phenotypically normal controls (tg/+ or +/+) were used for all the experiments (1 and 2), which employed respectively a radiochemical method (1) and in vitro recordings of field potentials from the pyramidal cells of hippocampal area CA₁ (2). Postsynaptic excitability as expressed by the PS/fEPSP input-output curves was found increased in tg/tg mice as compared to controls. Quantitative differences in the degree of synaptic activation of tg/tg versus controls were proved statistically non significant. Other significant findings irrespectively of epilepsy were: the indication that excitability increases with age during the reproductive period, the long term enhancement of postsynaptic excitability along with the induction of LTP due to NMDA receptor activation, and the independence of LTP induction process, in CA₁ hippocampal area, from any epileptiform activity. The second part is a pharmacological study aiming at the investigation of a possible cellular mechanism of action of six prorotype antiepileptics (Phenytoin, Carbamazepine, Phénobarbital, Ethosuximide, Valproate and Midazolam). The possibility of their exerting their antiepileptic action through NMDA receptor antagonism was examined. The results suggest that this is unlikely, the exception being Midazolam. The project took place by recording field potentials in vitro, from the hippocampal area CA₁ pyramidal cells of Wistar rats. The third part is an ontogenetic study aiming at the investigation of the participation of endogenous adenosine/adenosine receptors in synaptic potentials during CNS maturation. It was performed by recording CA₁ dendritic field potentials from hippocampal slices of Wistar rats aged 5, 10, 15, 20, 30 and 120 days. Synaptic potentials decreased in response to the application of 10μΜ Adenosine already from the age of 5 days and this effect remained quantitatively stable during development. The application of 100μΜ Caffeine (an adenosine competitive antagonist) enhanced the synaptic potentials in all the slices tested at 15, 20 and 30 days while it had no effect on half of the slices tested at 5 and 10 days. This finding indicates lower levels of endogenous adenosine in younger animals. Nitrobenzylthioinosine, an adenosine uptake blocker, at 50μΜ depressed the synaptic potentials and significantly enhanced the action of (exogenous) adenosine at all ages tested. Lower levels of endogenous adenosine in immature tissue might account for the increased excitability and tendency for epileptiform discharges observed during development.

Grantor dc:publisher

University of Patras

Year dc:date

1990

Authors dc:creator

• Psarropoulou, Caterina
• Ψαρροπούλου, Αικατερίνη

• Αδενοσίνη
• Αντιεπιληπτικά
• Επιληπτογένεση
• Ιόντα καλίου
• Ιππόκαμπος
• Μεταλλαγμένα επιληπτικά ποντίκια (Τόττερινγκ)
• Μμήμη (Long term potentiation)
• Οντογένεση
• Υποδοχείς Ν-Μεθύλ-D-ασπαρτικού
• Adenosine
• Antiepileptics
• Epileptogenesis
• Hippocampus
• Long term potentiation
• N-methyl-D-aspartate receptors
• Ontogenesis
• Potassium ions
• Tottering mice
• Ιατρική και Επιστήμες Υγείας
• Βασική Ιατρική
• Επιστήμες Υγείας
• Medical and Health Sciences
• Basic Medicine
• Health Sciences

Language dc:language

gre

Identifier

10.12681/eadd/1310

OAI identifier oai:identifier

oai:10442/1310