Increased immunoreactivity of glutamate receptors, neuronal nuclear protein and glial fibrillary acidic protein in the hippocampus of epileptic rats with fast ripple activity.

Abstract

Epilepsy is a neurological disorder in which an imbalance between excitatory and inhibitory transmission is observed. Glutamate is the principal excitatory neurotransmitter that acts through ionic and metabotropic receptors; both types of receptors are involved in temporal lobe epilepsy (TLE). High frequency oscillations called fast ripples (FR, 250-600\xa0Hz) have been observed, particularly in the hippocampus, and they are involved in epileptogenesis. The present study analyzed the immunoreactivity of the principal glutamate receptors associated with epilepsy in epileptic animals with FR activity. Male Swiss-Wistar rats (210-250 gr) were injected with pilocarpine (2.4\xa0mg/2\xa0µl) and were video monitored (24/7) until the appearance of spontaneous and recurrent seizures. Then, a deep microelectrode implantation surgery was performed in the DG, CA3 and CA1 regions, and FR activity was observed 1-, 2-, 3-, 7-, and 14-day postsurgery. The animals were sacrificed on day 15, and fluorescence immunohistochemistry was carried out in the hippocampus for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and mGlu-R5 glutamate receptors as well as Neuronal Nuclear Protein (NeuN) and Glial Fibrillary Acidic Protein (GFAP). An increase in the immunoreactivity for the three receptors was found. However, the AMPA receptor showed an increase in the three regions analyzed (i.e., DG, CA1 and CA3). The findings showed a decrease of NeuN in the DG and an increase of GFAP. These results suggest an important role of glutamate receptors in the hippocampus of epileptic rats with FR activity.