Changes of glial–neuronal interaction and metabolism after a subconvulsive dose of pentylenetetrazole

• Published in: Neurochemistry international 2004-10, Vol.45 (5), p.739-745
• Main Authors: Eloqayli, Haytham, Dahl, Carl Bredo, Götestam, K.Gunnar, Unsgård, Geirmund, Sonnewald, Ursula
• Format: Article
• Language: English
• Subjects: Acetates - pharmacology; Amino Acids - drug effects; Amino Acids - metabolism; Animals; Aspartate; Astrocytes - drug effects; Astrocytes - metabolism; Biological and medical sciences; Cell Communication - drug effects; Cell Communication - physiology; Cerebellum; Cerebellum - cytology; Cerebellum - drug effects; Cerebellum - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Chromatography, High Pressure Liquid; Convulsants - pharmacology; Epilepsy; Fundamental and applied biological sciences. Psychology; GABA; Glucose - pharmacology; Glutamate; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Magnetic Resonance Spectroscopy; Male; Medical sciences; Nervous system (semeiology, syndromes); Neuroglia - drug effects; Neuroglia - metabolism; Neurology; Neurons - drug effects; Neurons - metabolism; Pentylenetetrazole - pharmacology; PTZ; Pyruvate Carboxylase - metabolism; Pyruvate Dehydrogenase Complex - metabolism; Rats; Rats, Wistar; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2004.02.002

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.