Analysis of Differential Expression of Synaptic Vesicle Protein 2A in the Adult Rat Brain.

Synaptic vesicle protein 2A (SV2A), which plays an important role in the pathophysiology of epilepsy, is a unique vesicular protein recognized as a pharmacological target of anticonvulsant drugs. Furthermore, SV2A is a potential synaptic density marker, as it is ubiquitously expressed throughout the brain in all nerve terminals independently of their neurotransmitter content. Due to the growing interest in this protein, we thoroughly analyzed SV2A levels, expression patterns and colocalization in both excitatory and inhibitory synapses among different brain structures in healthy rats. In addition, we discuss the main semiquantitative methodologies used to study SV2A because these techniques might represent powerful tools for evaluating synaptic changes associated with brain disorders. Our results showed that the SV2A expression levels differed among the analyzed structures, and a positive correlation between the SV2A mRNA copy number and protein level was observed by Western blot. In addition, immunohistochemistry demonstrated slight but consistent asymmetrical SV2A levels in different laminated structures, and SV2A expression was increased by up to 40% in some specific layers compared to that in others. Finally, triple immunofluorescence revealed strong SV2A colocalization with GABAergic terminals, mainly around the principal cells, suggesting that SV2A primarily participates in this inhibitory system in different rat brain structures. Although the SV2A protein is considered a good candidate marker of synaptic density, our data show that changes in its expression in pathological processes must be viewed as not only increased or decreased synapse numbers but also in light of the type of neurotransmission being affected.