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Evidence that Hyperprolinemia Alters Glutamatergic Homeostasis in Rat Brain: Neuroprotector Effect of Guanosine

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Abstract

This study investigated the effects of acute and chronic hyperprolinemia on glutamate uptake, as well as some mechanisms underlying the proline effects on glutamatergic system in rat cerebral cortex. The protective role of guanosine on effects mediated by proline was also evaluated. Results showed that acute and chronic hyperprolinemia reduced glutamate uptake, Na+, K+-ATPase activity, ATP levels and increased lipoperoxidation. GLAST and GLT-1 immunocontent were increased in acute, but not in chronic hyperprolinemic rats. Our data suggest that the effects of proline on glutamate uptake may be mediated by lipid peroxidation and disruption of Na+, K+-ATPase activity, but not by decreasing in glutamate transporters. This probably induces excitotoxicity and subsequent energy deficit. Guanosine was effective to prevent most of the effects promoted by proline, reinforcing its modulator role in counteracting the glutamate toxicity. However, further studies are needed to assess the modulatory effects of guanosine on experimental hyperprolinemia.

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Acknowledgments

This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—Brazil) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS).

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Authors and Affiliations

  1. Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    Andréa G. K. Ferreira, Aline A. da Cunha, Emilene B. Scherer, Fernanda R. Machado, Maira J. da Cunha, Andressa Braga, Ben Hur Mussulini, Júlia D. Moreira, Susana Wofchuk, Diogo O. Souza & Angela T. S. Wyse

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  1. Andréa G. K. Ferreira
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  2. Aline A. da Cunha
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  11. Angela T. S. Wyse
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Correspondence to Angela T. S. Wyse.

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Ferreira, A.G.K., da Cunha, A.A., Scherer, E.B. et al. Evidence that Hyperprolinemia Alters Glutamatergic Homeostasis in Rat Brain: Neuroprotector Effect of Guanosine. Neurochem Res 37, 205–213 (2012). https://doi.org/10.1007/s11064-011-0604-1

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  • DOI: https://doi.org/10.1007/s11064-011-0604-1

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