Are astrocytes involved in the epileptogenesis?. The effects of thrombospondin receptor blockage in a model of temporal lobe epilepsy

ROSSI AR, ANGELO MF, VILLARREAL A, LUKIN J, REINES A, RAMOS AJ

London

Congreso; 10th European Congress on Epileptology; 2012

Purpose: Reactive astrocytes are known to secrete thrombospondins (TSP) that are specifically involved in the glutamatergic synaptogenesis. During the latency neuronal network reorganization is supposed to be the substrate for the epileptogenesis. In this study we evaluated if astrocytes and TSP are involved in the exacerbated neuronal plasticity that occurs during the latency period that precedes the final appearance of spontaneous recurrent seizures. Method: Using loss of function studies achieved by blocking the neuronal thrombospondin receptor alpha2delta1 with gabapentin (Gp) in rats exposed to the Lithium-pilocarpine model of temporal lobe epilepsy, we followed the changes in neuronal circuits and reactive gliosis. Adult male Wistar rats were treated with 3mEq/kg LiCl and 20h later with 30mg/kg pilocarpine (ip). 15 minutes after the onset of the status epilepticus (SE), they received 10mg/Kg diazepam. For the next 15 days animals received 400 mg/kg/day Gp or saline. In vitro, glio-neuronal hippocampal cultures were exposed to excitotoxic glutamate and subsequently to Gp (5, 25, 50 or 100 ug/ml) or vehicle. Result: During the latency, SE animals showed reactive gliosis, neuronal degeneration, ultrastructural alterations in synapses with atypical expression of synaptofisin (Syn) and increased level of plasticity marker PSA-NCAM in the hippocampus. Gp treatment reduced the alterations in Syn and PSA-NCAM but was unable to modify the neuronal loss and reactive gliosis. In glio-neuronal culture, Gp treatment partially prevented the dendritic loss caused by glutamate. Conclusion: The atypical synaptic morphology is probably related to the exacerbated neuronal plasticity