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Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy

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Abstract

Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5′-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy.

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Acknowledgments

This work was supported by the Brazilian funds from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Nº. 2006/06502-4 and 2006/61285-9), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES). We thank Hilda Silva Reis for technical assistance.

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Authors and Affiliations

  1. Departamento de Neurologia e Neurocirurgia, Disciplina de Neurociências, Universidade Federal de São Paulo, UNIFESP, Rua Pedro de Toledo, 669 – 2° andar, CEP 04039-032, São Paulo, Brazil

    Flávia Doná & Maria José da Silva Fernandes

  2. Laboratório de Reabilitação do Equilíbrio Corporal e Inclusão Social, Universidade Anhanguera de São Paulo (UNIAN), São Paulo, Brazil

    Flávia Doná

  3. Laboratório de Farmacologia, Instituto Butantan, São Paulo, Brazil

    Isaltino Marcelo Conceição, Thalma Ariani Freitas & Ana Leonor Abrahao Nencioni

  4. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil

    Henning Ulrich

  5. Departamento Fisiologia, Disciplina de Neurofisiologia e Fisiologia Endócrina, UNIFESP, São Paulo, Brazil

    Eliane Beraldi Ribeiro

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  1. Flávia Doná
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Correspondence to Maria José da Silva Fernandes.

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Animal protocols were conducted in accordance with national and international legislation (Guidelines of the Brazilian College of Animal Experimentation, COBEA; NIH Guide for Care and Use of Laboratory Animals) and with the approval of the Ethical Committee of the University (Protocol. 0636/04).

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Doná, F., Conceição, I.M., Ulrich, H. et al. Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy. Purinergic Signalling 12, 295–302 (2016). https://doi.org/10.1007/s11302-016-9504-9

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  • DOI: https://doi.org/10.1007/s11302-016-9504-9

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