Quinolinic acid promotes seizures and decreases glutamate uptake in young rats: reversal by orally administered guanosine
| Autor: | Juliana Moura Rodrigues, Emílio Hideyuki Moriguchi, Diogo Losch de Oliveira, Joel Felipe Horn, Marcos Emilio dos Santos Frizzo, Susana Tchernin Wofchuk, Diogo O. Souza |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
Aging medicine.medical_treatment Excitotoxicity Guanosine Administration Oral Down-Regulation Glutamic Acid Biology Pharmacology In Vitro Techniques medicine.disease_cause GABA Antagonists chemistry.chemical_compound Epilepsy medicine Animals Picrotoxin Drug Interactions Rats Wistar Molecular Biology Injections Intraventricular Neurons Dose-Response Relationship Drug General Neuroscience Glutamate receptor Brain Quinolinic Acid medicine.disease Rats Disease Models Animal Anticonvulsant medicine.anatomical_structure chemistry Animals Newborn Anesthesia Phenobarbital Anticonvulsants Female Neurology (clinical) Excitatory Amino Acid Antagonists Developmental Biology Quinolinic acid Astrocyte medicine.drug |
| Zdroj: | Brain research. 1018(1) |
| ISSN: | 0006-8993 |
| Popis: | Quinolinic acid (QA) has been used as a model for experimental overstimulation of the glutamatergic system. Glutamate uptake is the main mechanism involved in the maintenance of extracellular glutamate below toxic levels. Guanosine systemically administered prevents quinolinic acid-induced seizures in adult mice and increases basal glutamate uptake by cortical astrocyte culture and slices from young rats. The immature brain differs from the adult brain in its susceptibility to seizures, seizure characteristics, and responses to antiepileptic drugs (AED). Here we investigated the effect of guanosine p.o. on QA-induced seizures in young rats (P12–14) and upon ex vivo glutamate uptake by cortical slices from these animals. I.c.v. infusion of 250 nmol QA induced seizures in all animals and decreased glutamate uptake. I.p. injection of MK-801 and phenobarbital 30 min before QA administration prevented seizures in all animals. Guanosine (7.5 mg/kg) 75 min before QA prevented seizures in 50% of animals as well as prevented the decrease of glutamate uptake in the protected animals. To investigate if the anticonvulsive effect of guanosine was specific for QA-induced seizures, the picrotoxin-induced seizures model was also performed. Pretreatment with phenobarbital i.p. (60 mg/kg–30 min) prevented picrotoxin-induced seizures in all animals, whereas guanosine p.o. (7.5 mg/kg–75 min) and MK-801 i.p. (0.5 mg/kg–30 min) had no effect. Thus, guanosine protection on the QA-induced seizures in young rats and on the decrease of glutamate uptake showed some specificity degree towards the QA-induced toxicity. This points that guanosine could be considered for treatments of epilepsy, and possibly other neurological disorders in children. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect