Neurobiology Research Unit, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark; Physiology Department, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkey.
Neurobiology Research Unit, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Epilepsy Res. 2022 Jul;183:106926. doi: 10.1016/j.eplepsyres.2022.106926. Epub 2022 Apr 21.
Synaptic Vesicle Glycoprotein 2A (SV2A) has been proposed as a presynaptic marker in several neurological disorders. Not only is SV2A the target for the antiepileptic drug levetiracetam, but also considered a marker of mature pre-synapses. In this study, we aimed to assess the binding of [H]UCB-J as a selective radioligand for SV2A to visualize and determine changes during different stages of epileptogenesis by in-vitro autoradiography in rat models of temporal lobe epilepsy. Two different kainic acid (KA) injection routes were used to model temporal lobe epilepsy in the rat; a systemic (10 mg/kg KA injected intraperitoneally) and a local model (1.875 mM KA injected intrahippocampally). Brain tissue was sampled at different time points after the initial status epilepticus and semi-quantitative [H]UCB-J autoradiography was performed to determine temporal and spatial changes under the progression of epileptogenesis. A decrease in [H]UCB-J binding was observed in many brain areas in the acute phases after both types of kainic acid administration. Peak reductions occurred slightly before in systemic-treated animals (within 3-10 days) than after local-treated animals (within 5-15 days). Interestingly in the systemic model, we observed a full restoration in the binding level 30 days after the treatment in most areas probably reflecting neuronal reorganization. However, after the local injection in the hippocampus, the binding in the hippocampus, and in temporal and piriform cortices did not return to basal levels. The time-course profile displayed lateralization in the local model. These results demonstrate changes in the amount of a presynaptic SV2A binding site after seizures and suggest that SV2A may have importance in eliciting spontaneous seizures and/or be a biomarker for epileptogenesis. The present study shows that SV2A is a biomarker of acute phase epileptogenesis in specific brain regions.
突触小泡糖蛋白 2A（SV2A）已被提出作为几种神经疾病的突触前标志物。SV2A 不仅是抗癫痫药物左乙拉西坦的靶点，而且被认为是成熟突触前的标志物。在这项研究中，我们旨在评估 [H]UCB-J 作为 SV2A 的选择性放射性配体的结合情况，通过在颞叶癫痫大鼠模型中的体外放射自显影来观察和确定在癫痫发生的不同阶段的变化。两种不同的海人酸（KA）注射途径用于在大鼠中模拟颞叶癫痫；全身（10mg/kg KA 腹腔内注射）和局部模型（1.875mM KA 海马内注射）。在初始癫痫持续状态后不同时间点采集脑组织，并进行 [H]UCB-J 放射自显影半定量分析，以确定在癫痫发生过程中的时间和空间变化。在两种类型的 KA 给药后的急性相，观察到许多脑区 [H]UCB-J 结合减少。在全身治疗动物中（3-10 天内），峰值减少发生得稍早，而在局部治疗动物中（5-15 天内）。有趣的是，在全身模型中，我们观察到在治疗后 30 天大多数区域的结合水平完全恢复，这可能反映了神经元的重组。然而，在海马内注射后，海马内以及颞叶和梨状皮质的结合并未恢复到基础水平。局部模型中的时间过程显示出偏侧化。这些结果表明癫痫发作后突触前 SV2A 结合位点数量发生变化，并表明 SV2A 可能在引发自发性癫痫发作中具有重要作用，或者是癫痫发生的生物标志物。本研究表明，SV2A 是特定脑区急性相癫痫发生的生物标志物。
