Contrasting effects of Na+, K+-ATPase activation on seizure activity in acute versus chronic models
| Autor: | Ana Flávia Furian, J.W. Larrick, Luiz Fernando Freire Royes, Iuri Domingues Della-Pace, Leandro Rodrigo Ribeiro, Mauro Schneider Oliveira, C.V. de Oliveira, Michele Rechia Fighera, Jéssica Grigoletto, Letícia Meier Pereira, Vinícius Rafael Funck |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Time Factors Population Hippocampus Convulsants Status epilepticus Hippocampal formation Pharmacology Antibodies Gene Expression Regulation Enzymologic Statistics Nonparametric Epilepsy Status Epilepticus medicine Animals Na+/K+-ATPase Pentylenetetrazol education education.field_of_study Chemistry General Neuroscience Pilocarpine Electroencephalography medicine.disease Brain Waves Rats Mice Inbred C57BL Disease Models Animal Pentylenetetrazole Anticonvulsants medicine.symptom Sodium-Potassium-Exchanging ATPase medicine.drug |
| Zdroj: | Neuroscience. 298 |
| ISSN: | 1873-7544 |
| Popis: | 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 α subunit would decrease seizure susceptibility. We found that incubation of hippocampal homogenates with DRRSAb (1 μM) increased total and α1 Na(+), K(+)-ATPase activities. A higher concentration (3 μM) increased total, α1 and α2/α3 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. |
| Databáze: | OpenAIRE |
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