Rapid compensatory changes in the expression of EAAT-3 and GAT-1 transporters during seizures in cells of the CA1 and dentate gyrus

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Abstract

BACKGROUND: Epilepsy is a neurological disorder produced by an imbalance between excitatory and inhibitory neurotransmission, in which transporters of both glutamate and GABA have been implicated. Hence, at different times after local administration of the convulsive drug 4-aminopyridine (4-AP) we analyzed the expression of EAAT-3 and GAT-1 transporter proteins in cells of the CA1 and dentate gyrus.<br /><br />METHODS: Dual immunofluorescence was used to detect the co-localization of transporters and a neuronal marker. In parallel, EEG recordings were performed and convulsive behavior was rated using a modified Racine Scale.<br /><br />RESULTS: By 60 min after 4-AP injection, EAAT-3/NeuN co-labelling had increased in dentate granule cells and decreased in CA1 pyramidal cells. In the latter, this decrease persisted for up to 180 min after 4-AP administration. In both the DG and CA1, the number of GAT-1 labeled cells increased 60 min after 4-AP administration, although by 180 min GAT-1 labeled cells decreased in the DG alone. The increase in EAAT-3/NeuN colabelling in DG was correlated with maximum epileptiform activity and convulsive behavior.<br /><br />CONCLUSIONS: These findings suggest that a compensatory mechanism exists to protect against acute seizures induced by 4-AP, whereby EAAT-3/NeuN cells is rapidly up regulated in order to enhance the removal of glutamate from the extrasynaptic space, and attenuating seizure activity.

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Medina-Ceja, L., Sandoval-García, F., Morales-Villagrán, A., & Lápez-Pérez, S. J. (2012). Rapid compensatory changes in the expression of EAAT-3 and GAT-1 transporters during seizures in cells of the CA1 and dentate gyrus. Journal of Biomedical Science, 19(1). https://doi.org/10.1186/1423-0127-19-78

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