Concomitant increase of somatostatin, neuropeptide Y and glutamate decarboxylase in the frontal cortex of rats with decreased seizure threshold.
The neuropeptides somatostatin and neuropeptide Y and the activity of glutamate decarboxylase were determined in the frontal cortex of rats subjected to experimental epilepsy. Two different animal models, (1) rats kindled for 4 weeks by daily injection of pentylenetetrazole, and (2) rats which had undergone strong limbic seizures induced by kainic acid, were used. Decreased seizure threshold, as shown by injection of a subconvulsive dose of pentylenetetrazole, was observed 10 days after the last kindling session and 1 month after injection of kainic acid, respectively. Significantly increased levels of somatostatin (by 60%), neuropeptide Y (135%) and increased activity of glutamate decarboxylase (22%) were found in the frontal cortex of rats previously treated with kainic acid. Separation of somatostatin-like immunoreactivity by size exclusion high-performance liquid chromatography showed a marked increase of immunoreactivity in fractions containing the somatostatin precursor (by 200%) and less prominently of somatostatin-14 and somatostatin-28 (by 60 and 80%, respectively). Michaelis-Menten kinetics of glutamate decarboxylase revealed an increased maximal velocity (Vmax) in the frontal cortex of kainic acid-treated rats, but no change in the Km value was found. Similar results were also obtained in pentylenetetrazole-kindled rats. Injection of cysteamine (100 mg/kg, i.p.) resulting in a 30% decrease of cortical somatostatin in kainic acid-pretreated rats markedly suppressed seizures induced by an otherwise subconvulsive dose of pentylenetetrazole.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003543:Cysteamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D007608:Kainic Acid; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism*; D013997:Time Factors
D009478:Neuropeptide Y; D013004:Somatostatin; D003543:Cysteamine; D005968:Glutamate Decarboxylase; D007608:Kainic Acid; D010433:Pentylenetetrazole