Changes of glial-neuronal interaction and metabolism after a subconvulsive dose of pentylenetetrazole.
Pentylenetetrazole (PTZ) injection causes seizures in rodents and this is used in several models of epilepsy. In the present study a low dose (20 mg/kg) was injected into rats in order to analyze metabolic disturbances caused by subconvulsive amounts of PTZ. Intraperitoneal injection of PTZ was followed, 30 min later, by injection of [1-(13C)]glucose plus [1,2-(13C)]acetate and 15 min thereafter decapitation. Analyses of extracts from cerebrum, subcortex and cerebellum were performed using 13C NMRS and HPLC. Whereas convulsive doses of PTZ lead to most pronounced changes in cerebellum [J. Neurochem. 85 (2003) 1200], it could be shown that subconvulsive doses affected mainly amino acid metabolism in cerebrum. In glutamatergic neurons in the cerebrum PTZ affected both the metabolic and releasable pools of glutamate, whereas, in the subcortex and cerebellum only the metabolic pool was affected. This could be deducted from the findings that less [4-(13C)]glutamine, [3,4-(13C)]glutamate and [2-(13C)]aspartate, which are labeled from [1-(13C)]glucose, were detected in this area. Glial metabolism was also changed as evidenced by the decreased pyruvate carboxylation versus pyruvate dehydrogenation ratio both in cerebrum and subcortex. Comparison between convulsive and nonconvulsive doses of PTZ lead to the hypothesis that changes observed in the cerebellum are mainly due to seizures, whereas those in cerebrum and subcortex are coupled to the action of the chemical stimulant.
Eloqayli
Haytham
H
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Olav Kyrregst 3, NO-7489 Trondheim, Norway.
Dahl
Carl Bredo
CB
Götestam
K Gunnar
KG
Unsgård
Geirmund
G
Sonnewald
Ursula
U
D000085:Acetates / Q000494:pharmacology; D000596:Amino Acids / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003292:Convulsants / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000494:pharmacology*; D011766:Pyruvate Carboxylase / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D000596:Amino Acids; D003292:Convulsants; D011768:Pyruvate Dehydrogenase Complex; D011766:Pyruvate Carboxylase; D005947:Glucose; D010433:Pentylenetetrazole