Purpose: We previously showed that gene expression of synaptic vesicle protein 2A (SV2A), the binding site for the antiepileptic
drug levetiracetam, is reduced during epileptogenesis in the rat. Since absence of SV2A has been associated with increased
epileptogenicity, changes in expression of SV2A could have consequences for the progression of epilepsy. Therefore we investigated
hippocampal SV2A protein expression of temporal lobe epilepsy (TLE) patients and in rats during epileptogenesis and in the
chronic epileptic phase.
Methods: SV2A immunocytochemistry and Western blot analysis were performed on the hippocampus
of autopsy controls, patients that died from status epilepticus (SE), and pharmacoresistant TLE patients. In addition, in
epileptic rats, SV2A expression was determined after SE during the acute, latent, and chronic epileptic phase.
In control tissue, presynaptic SV2A was expressed in all hippocampal subfields, with strongest expression in mossy fiber terminals.
SV2A positive puncta were distributed in a patchy pattern over the somata and dendrites of neurons. SV2A decreased throughout
the hippocampus of TLE patients with hippocampal sclerosis (HS), compared to autopsy control, SE, and non-HS tissue. In most
rats, SV2A was already decreased in the latent period especially in the inner molecular layer and stratum lucidum. Similarly
as in humans, SV2A was also decreased throughout the hippocampus of chronic epileptic rats, specifically in rats with a progressive
form of epilepsy.
Discussion: These data support previous findings that reduced expression of SV2A could contribute to
the increased epileptogenicity. Whether this affects the effectiveness of levetiracetam needs to be further investigated.