Abstract
Synaptic vesicle protein 2A (SV2A), the target of the antiepileptic drug levetiracetam (LEV), is expressed ubiquitously in all synaptic terminals. Its levels decrease in patients and animal models of epilepsy. Thus, changes in SV2A expression could be a critical factor in the response to LEV. Epilepsy is characterized by an imbalance between excitation and inhibition, hence SV2A levels in particular terminals could also influence the LEV response. SV2A expression was analyzed in the epileptic hippocampus of rats which responded or not to LEV, to clarify if changes in SV2A alone or together with glutamatergic or GABAergic markers may predict LEV resistance. Wistar rats were administered saline (control) or pilocarpine to induce epilepsy. These groups were subdivided into untreated or LEV-treated groups. All epileptic rats were video-monitored to assess their number of seizures. Epileptic rats with an important seizure reduction (>50%) were classified as responders. SV2A, vesicular γ-aminobutyric acid transporter and vesicular glutamate transporter (VGLUT) expression were assessed by immunostaining. SV2A expression was not modified during epilepsy. However, responders showed ≈55% SV2A-VGLUT co-expression in comparison with the non-responder group (≈40%). Thus, SV2A expression in glutamatergic terminals may be important for the response to LEV treatment.
Highlights
A microarray analysis of the hippocampus in epileptic patients not responding to LEV treatment shows overexpression of Sv2a and other genes encoding proteins involved in vesicle trafficking. This suggests that adequate expression levels of these proteins must be maintained for proper endocytosis, as well as LEV action [27]. These results indicate that any change in Synaptic vesicle protein 2A (SV2A) expression may participate in the pathogenesis and treatment of epilepsy
The results showed that epileptic of seizures in treated epileptic rats were compared with Mann–Whitney rank sum a rats have at least 3 seizures per week
EPI+LEV rats, in order to determine if alterations in SV2A protein expression associat to epilepsy may be important for LEV effectiveness
Summary
Synaptic vesicle protein 2A (SV2A) is an essential membrane protein, universal to all types of neuronal terminals [1,2]. Its exact physiological function is not completely known. Some reports show that SV2A participates in the synaptic vesicle cycle. It may be involved in vesicular priming [2,3], enhancing the probability of neurotransmitter release at presynaptic terminals [4] and regulating action potential calcium-dependent neurotransmitter release [5,6]. SV2A participates in the modulation of endocytosis by regulating the expression and trafficking of synaptotagmin (a Ca2+ sensor protein) after
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