Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy

Erwin A. Van Vliet; Eleonora Aronica; Sandra Redeker; Karin Boer; Jan A. Gorter

doi:10.1111/j.1528-1167.2008.01727.x

journal article Mar 01, 2009

Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy

Erwin A. Van Vliet Eleonora Aronica

Sandra Redeker Karin Boer Jan A. Gorter

Epilepsia Vol. 50 No. 3 pp. 422-433 · Wiley

View at Publisher Save 10.1111/j.1528-1167.2008.01727.x

Abstract

SummaryPurpose: 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.Results: 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.

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Details

Published: Mar 01, 2009
Vol/Issue: 50(3)
Pages: 422-433
License: View

Authors

Cite This Article

Erwin A. Van Vliet, Eleonora Aronica, Sandra Redeker, et al. (2009). Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy. Epilepsia, 50(3), 422-433. https://doi.org/10.1111/j.1528-1167.2008.01727.x

Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy

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