Journal
NEUROSCIENCE
Volume 298, Issue -, Pages 171-179Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2015.04.031
Keywords
epilepsy; pilocarpine; seizure; EEG; sodium pump
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [ARD 11/1630-1, PRONEM 11/2082-4]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [471666/2013-0]
- Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES)
- CNPq/Pibic
- Fapergs/Probic
- CNPq
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Epilepsy is a life-shortening brain disorder affecting approximately 1% of the worldwide population. Most epilepsy patients are refractory to currently available antiepileptic drugs (AEDs). Knowledge about the mechanisms underlying seizure activity and probing for new AEDs is fundamental to the discovery of new therapeutic strategies. Brain Na+, K+-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. Accordingly, a decrease of Na+, K+-ATPase increases neuronal excitability and may predispose to appearing of seizure activity. In the present study, we tested the hypothesis that activation of Na+, K+-ATPase activity with a specific antibody (DRRSAb) raised against a regulatory site in the a subunit would decrease seizure susceptibility. We found that incubation of hippocampal homogenates with DRRSAb (1 mu M) increased total and alpha 1 Na+, K+-ATPase activities. A higher concentration (3 mu M) increased total, a1 and alpha 2/alpha 3 Na+, K+-ATPase activities. Intrahippocampal injection of DRRSAb decreased the susceptibility of post status epilepticus animals to pentylenetetrazol (PTZ)-induced myoclonic seizures. In contrast, administration of DRRSAb into the hippocampus of naive animals facilitated the appearance of PTZ-induced seizures. Quantitative analysis of hippocampal electroencephalography (EEG) recordings revealed that DRRSAb increased the percentage of total power contributed by the delta frequency band (0-3 Hz) to a large irregular amplitude pattern of hippocampal EEG. On the other hand, we found no DRRSAb-induced changes regarding the theta functional state. Further studies are necessary to define the potential of Na+, K+-ATPase activation as a new therapeutic approach for seizure disorders. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
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