Down-regulation Synaptic Vesicle Protein 2A in the Anterior Temporal Neocortex of Patients with Intractable Epilepsy

Abstract

Synaptic vesicle protein 2A (SV2A) involvement has been reported in the animal models of epilepsy. The aim of this study was to investigate the expression of SV2A in human intractable epilepsy (IE) brain tissue. Using immunohistochemistry, immunofluorescence, and Western blot, we detected SV2A expression in tissue samples from the anterior temporal neocortex of 33 patients who had been surgically treated for IE. We compared these tissues with nine histologically normal anterior temporal lobe samples from controls. SV2A immunoreactive staining was 0.1651+/-0.0564 in patient group and 0.2347+/-0.0187 in the control group (p<0.05) using immunohistochemistry, and this finding was consistently observed with Western blot analysis (0.1727 +/- 0.0471 versus 0.3976+/-0.0983, p<0.05). Immunofluorescence staining showed that SV2A was mainly accumulated in neurons. Our findings demonstrate that down-regulation of SV2A is present in patients with temporal lobe epilepsy.

Overexpression of Synaptic Vesicle Protein 2A Inhibits Seizures and Amygdaloid Electroencephalogram Activity in Pilocarpine-induced Pharmacoresistant Epileptic Rats

“…Thus, the pharmacoresistant epileptic rats displayed significant decreases in levels of SV2A. These findings are consistent with those obtained from brain tissues of patients with pharmacoresistant epilepsy [8,9]. Given that the absence of SV2A in knockout mice is associated with development of seizures, we speculate that the observed decrease of SV2A expression might be the mechanism underlying progression of refractory epilepsy.…”

“…Decreased SV2A was observed in brain tissues of patients with intractable epilepsy and may also contribute to the progression of epilepsy [8,9,35]. Similarly, SV2A was decreased throughout the hippocampus of epileptic rats, particularly in the chronic epileptic phase.…”

“…Gene expression of SV2A is reduced during epileptogenesis in the rat, and changes in expression of SV2A may have consequences for progression of epilepsy [8]. Recent studies have found downregulation of SV2A expression in brain tissue obtained from patients with intractable temporal lobe epilepsy [6,9]. Several lines of evidence suggest that SV2A is the binding site for the antiepileptic drug levetiracetam (LEV) [10,11].…”

Synaptic Vesicle Glycoprotein 2A Ligands in the Treatment of Epilepsy and Beyond

“…As in post-SE rat models of TLE (see Sect. 3.1), SV2A expression was reduced by 30–50 % in the anterior temporal neocortex of adult patients with TLE [54]. Weak SV2A immunoreactivity (IR) was observed in the tissue from TLE patients, whereas strong IR was present in brain tissue from control patients [54].…”

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

“…Decreased SV2A was observed in surgically removed temporal lobe tissue and postmortem hippocampal tissue from patients with temporal lobe epilepsy (Feng et al, 2009;van Vliet et al, 2009). Levetiracetam is a unique antiepileptic drug that targets a synaptic vesicle protein instead of other antiepileptics that block voltagegated sodium channels or modulate GABA receptors (Fig.…”