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Intracerebroventricular Guanine-Based Purines Protect Against Seizures Induced by Quinolinic Acid in Mice

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Abstract

Acute and chronic administration of the nucleoside guanosine have been shown to prevent quinolinic acid (QA) and α-dendrotoxin-induced seizures, as well as to impair memory and anxiety in rats and mice. In this study, we investigated the effect of i.c.v. administration of guanine-based purines (GTP, GDP, GMP, and guanosine) against seizures induced by the NMDA agonist and glutamate releaser quinolinic acid in mice. We also aimed to study the effects of the poorly hydrolysable analogs of GTP (GppNHp and GTPγS) and GDP (GDPβS) in this seizure model. QA produced seizures in 100% of mice, an effect partially prevented by guanine-based purines. In contrast to GTP (480 nmol), GDP (320–640 nmol), GMP (320–480 nmol) and guanosine (300–400 nmol), the poorly hydrolysable analogs of GTP and GDP did not affect QA-induced seizures. Thus, the protective effects of guanine nucleotides seem to be due to their conversion to guanosine. Altogether, these findings suggest a potential role of guanine-based purines for treating diseases involving glutamatergic excitotoxicity.

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Authors and Affiliations

  1. Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    André P. Schmidt, Thiago T. Ávila & Diogo O. Souza

  2. André P. Schmidt, Avenida Ramiro Barcelos, 2600-Anexo, Zip Code 90035-003, Porto Alegre, RS, Brazil

    André P. Schmidt

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  1. André P. Schmidt
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  2. Thiago T. Ávila
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Correspondence to André P. Schmidt.

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Schmidt, A.P., Ávila, T.T. & Souza, D.O. Intracerebroventricular Guanine-Based Purines Protect Against Seizures Induced by Quinolinic Acid in Mice. Neurochem Res 30, 69–73 (2005). https://doi.org/10.1007/s11064-004-9687-2

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