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A ketogenic diet did not prevent effects on the ectonucleotidases pathway promoted by lithium-pilocarpine-induced status epilepticus in rat hippocampus

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Abstract

A Ketogenic Diet (KD) mimics the anticonvulsant effects of fasting, which are known to suppress seizures. The purinergic system has been investigated in the matter of epilepsy development, especially the nucleoside adenosine, which has been considered a natural brain anticonvulsant. During epileptic seizures, extracellular adenosine concentration rises rapidly to micromolar levels. Adenosine can exert its anticonvulsant functions, after its release by nucleoside bidirectional transport, or by production through the sequential catabolism of ATP by ectonucleotidases, such as E-NTPDases (ectonucleoside triphosphate diphosphohydrolases) and ecto-5′-nucleotidase. Here, we have investigated the effect of a ketogenic diet on the nucleotide hydrolysis and NTPDases expression in the lithium-pilocarpine (Li-Pilo) model of epilepsy. For the induction of Status Epileticus (SE), 21-day-old female Wistar rats received an i.p. injection of lithium chloride (127 mg/kg) and 18–19 h later an i.p. injection of pilocarpine hydrochloride (60 mg/kg). The control groups received an injection of saline. After induction of SE, the control and Li-Pilo groups received standard or ketogenic diets for 6 weeks. The lithium-pilocarpine exposure affected the ATP (a decrease of between 8 % and 16 %) and ADP (an increase of between 18 % and 22 %) hydrolysis in both groups whereas the diet did not impact the nucleotide hydrolysis. NTPDase2 and 3 mRNA expressions decreased in the Li-Pilo group (41 % and 42 %). This data highlights the participation of the purinergic system in the pathophysiology of this model of epilepsy, since nucleotide hydrolysis and NTPDase expressions were altered by Li-Pilo exposure, with no significant effects of the ketogenic diet. However, the interaction between purinergic signaling and a ketogenic diet on epilepsy still needs to be better elucidated.

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Acknowledgments

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Vanessa Gass da Silveira was recipient of a CNPq fellowship.

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-anexo, CEP 90035-003, Porto Alegre, RS, Brazil

    Vanessa Gass da Silveira, Giana de Paula Cognato, Fabrício Figueiró, Marcos Luis Santos Perry & Ana Maria Oliveira Battastini

  2. Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Caixa Postal 1429, 90619-900, Porto Alegre, RS, Brazil

    Rosane Souza da Silva, Katiucia Marques Capiotti, Mauricio Reis Bogo & Carla Denise Bonan

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  1. Vanessa Gass da Silveira
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  2. Rosane Souza da Silva
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  3. Giana de Paula Cognato
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  4. Katiucia Marques Capiotti
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  5. Fabrício Figueiró
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  7. Carla Denise Bonan
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  8. Marcos Luis Santos Perry
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  9. Ana Maria Oliveira Battastini
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Correspondence to Ana Maria Oliveira Battastini.

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da Silveira, V.G., da Silva, R.S., de Paula Cognato, G. et al. A ketogenic diet did not prevent effects on the ectonucleotidases pathway promoted by lithium-pilocarpine-induced status epilepticus in rat hippocampus. Metab Brain Dis 27, 471–478 (2012). https://doi.org/10.1007/s11011-012-9333-7

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  • DOI: https://doi.org/10.1007/s11011-012-9333-7

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