Expression patterns of synaptic vesicle protein 2A in focal cortical dysplasia and TSC-cortical tubers

Purpose: Synaptic vesicle protein 2A (SV2A), the binding site for the antiepileptic drug (AED) levetiracetam, has been shown to be involved in the control of neuronal excitability. The aim of the study was to define the expression and cell-specific distribution of SV2A in developmental focal lesions associated with medically intractable epilepsy. Methods: SV2A immunocytochemistry and Western blotting was performed in focal cortical dysplasia (FCD type IIB) and cortical tubers from patients with tuberous sclerosis complex (TSC). Results: Autopsy and surgical control neocortical specimens were characterized by strong SV2A immunoreactivity throughout all cortical layers, with punctate labeling around the somata and dendrites of neurons. In FCD and cortical tuber specimens less intense, SV2A immunoreactivity was observed in the neuropil. The reduction in expression was confirmed by Western blot analysis. In both FCD and tuber specimens, clusters of punctate labeling were detected along cell borders and processes (perisomatic synapses) of dysplastic neuronal cells localized in both gray and white matter. The large majority of balloon cells in FCD, or giant cells in tubers, did not show punctate labeling around their somata. SV2A immunoreactivity was observed occasionally within the neuronal perikarya. Conclusions: The pattern of SV2A immunoreactivity with reduced neuropil expression and altered cellular and subcellular distribution suggests a possible contribution of SV2A to the epileptogenicity of these malformations of cortical development. Knowledge of the expression pattern of SV2A in epilepsy-associated pathologies may be valuable for the evaluation of the effectiveness of AEDs targeting this protein.