PAF receptor activation in hippocampal plasticity induced by SE

Abstract

One of the defining characteristics of epilepsy is abberant mossy fiber sprouting (MFS) in the dentate gyrus. These axonal projections within the granule cell layer of the dentate gyrus create a hyperexcitable network and lead to spontaneous seizures. Growth‐associated protein 43 (GAP‐43), a presynaptic marker that is expressed during development and axonal growth, has been preveiously implicated in the abnormal MFS found in epileptic models. The purpose of our study is to investigate the role of platelet activating factor (PAF) receptor‐mediated signaling in abnormal MFS by evaulating GAP‐43 immunoreactivity. PAF is a mediator of inflammation, a potent gene expression inducer and a modulator of long term potentiation (LTP), synaptic plasticity, and memory formation. PAF abnormally accumulates in the brain during seizures, or injuries, contributing to neuroinflammation and neurotoxicity. Using the novel PAF receptor antagonist, LAU‐0901, in the rat pilocarpine model of epilepsy, we found a positive correlation between a decrease in spontenous seizure activity and an increase GAP‐43 immunoreacitivy in our treated group, suggesting that PAF receptor activation is involved in the abberant plasticity associated with epilepsy.Source of support: This work was supported by NIH/NCRR grant P20 RR016816.