Laboratory of Neuropathology, GIGA-Neurosciences, University of Liege, Liege, Belgium; Laboratory of Developmental Neurobiology, GIGA-Neurosciences, University of Liege, Liege, Belgium.
Neuropathol Appl Neurobiol. 2014 Feb;40(2):191-204. doi: 10.1111/nan.12054.
Synaptic vesicle proteins 2 (SV2) are neuronal vesicles membrane glycoproteins that appear as important targets in the treatment of partial and generalized epilepsies. Therefore, we analysed the expression of SV2 isoforms in the hippocampus of patients with temporal lobe epilepsy (TLE).
SV2A, SV2B and SV2C immunostaining and QuantiGene branched DNA assay were performed on biopsies from 31 consecutive TLE patients with mesial temporal sclerosis (MTS) and compared with 10 autopsy controls. SV2 expression was further compared with Timm's staining, and synaptophysin, Zinc transporter 3 (ZnT3), dynorphin, vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter (VGAT) expression.
In TLE patients, SV2A and SV2B expression was decreased in areas of synaptic loss. SV2C, which is weakly expressed or absent in the hippocampus of controls, was overexpressed in 10/11 cases with classical MTS1A and mossy fibre sprouting but not in cases with other types of MTS. SV2C staining was located in the inner molecular layer of the dentate gyrus and colocalized with dynorphin, ZnT3 and VGLUT1, suggesting selective expression in presynaptic glutamatergic Zn(2+) -rich terminals of abnormal sprouting fibres. SV2 expression patterns correlated with histological subtypes of MTS, but not with clinical features or therapeutic regimens in this patient cohort.
In classical MTS1A, the expression of SV2 isoforms is altered with a marked decrease of SV2A and SV2B paralleling synaptic loss and a selective increase of SV2C in sprouting mossy fibres. These findings suggest a different physiology of sprouting synapses and the possibility to target them with SV2C-specific strategies.
突触小泡蛋白 2（SV2）是神经元囊泡膜糖蛋白，作为部分和全面性癫痫治疗的重要靶点。因此，我们分析了颞叶癫痫（TLE）患者海马 SV2 同工型的表达。
对 31 例伴有内侧颞叶硬化（MTS）的 TLE 患者连续活检标本进行 SV2A、SV2B 和 SV2C 免疫染色和 Quantigene 分支 DNA 检测，并与 10 例尸检对照进行比较。进一步比较了 SV2 的表达与 Timm 染色以及突触小体蛋白、锌转运蛋白 3（ZnT3）、强啡肽、囊泡谷氨酸转运体 1（VGLUT1）和囊泡 GABA 转运体（VGAT）的表达。
在 TLE 患者中，SV2A 和 SV2B 的表达在突触丧失区域减少。SV2C 在对照组海马中弱表达或缺失，但在 11 例具有经典 MTS1A 和苔藓纤维发芽的病例中过度表达，但在其他类型的 MTS 病例中没有。SV2C 染色位于齿状回的内分子层，与强啡肽、ZnT3 和 VGLUT1 共定位，提示选择性表达在异常发芽纤维的突触前谷氨酸能 Zn(2+)丰富的末端。SV2 的表达模式与 MTS 的组织学亚型相关，但与该患者队列的临床特征或治疗方案无关。
在经典的 MTS1A 中，SV2 同工型的表达发生改变，SV2A 和 SV2B 的表达显著减少，与突触丧失平行，发芽苔藓纤维中的 SV2C 选择性增加。这些发现表明发芽突触的生理学不同，并有可能针对它们使用 SV2C 特异性策略。
