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ToxSci Advance Access published online on April 15, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg058
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received October 25, 2002; accepted February 4, 2003
© 2003 Society of Toxicology

Neurotoxicology

Methylmercury Increases Glutamate Release from Brain Synaptosomes and Glutamate Uptake by Cortical Slices from Suckling Rat Pups: Modulatory Effect of Ebselen

M. Farina 1*, K. C. S. Dahm 1, F. D. Schwalm 1, A. M. Brusque 1, M. E. S. Frizzo 1, G. Zeni 2, D. O. Souza 1, J. B. T. Rocha 2

1 Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil
2 Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil

* To whom correspondence should be addressed. E-mail: marcelofarina{at}zipmail.com.br.


  Abstract

During the early post-natal period the brain is extremely sensitive to external agents. Here, we examined the effect of subcutaneous injections of methylmercury (MeHg; 2 mg/kg) during the suckling period - postnatal day (PND) 3-10, 3-17 or 3-24 - on glutamate release from brain synaptosomal preparations and on glutamate uptake by brain cortical slices of rat pups. The possible antagonist effect of ebselen against MeHg effect was also examined at PND 24. MeHg increased the basal (but not K+-stimulated) glutamate release and glutamate uptake at PND 24. A strong tendency of increase in the basal glutamate release from synaptosomes (P=0.088) was observed at PND 17. Ebselen, which did not affect glutamate release and uptake per se, prevented both effects of MeHg. This study indicates that: i) the effect of MeHg on glutamate release could be involved in its toxicity; ii) the increase in the glutamate uptake could represent a pathophysiological response to MeHg-induced glutamate release; iii) the inhibitory effect of ebselen on MeHg-induced glutamate release could be related to its reported neuroprotective effects.

methylmercury, ebselen, glutamate uptake, glutamate release, cortical slices, synaptosomes .


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