Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Neurosci Lett. 2012 Feb 29;510(2):93-8. doi: 10.1016/j.neulet.2012.01.009. Epub 2012 Jan 13.
Immunohistochemical studies were performed to analyze the expressional changes in hippocampal synaptic vesicle protein 2A (SV2A) following pentylenetetrazole (PTZ) kindling. Repeated treatments of mice with sub-convulsive PTZ (40 mg/kg, i.p.) for 15 days progressively enhanced seizure susceptibility and induced clonic convulsions in most animals examined. Topographical analysis of hippocampal SV2A-immunoreactivity revealed that SV2A was densely expressed in the hilar region of the dentate gyrus, stratum lucidum of the CA3 field and around the periphery of CA3 pyramidal neurons. PTZ kindling region-specifically increased SV2A expression in the dentate hilus without affecting that in the stratum lucidum or the pyramidal cell layer of the CA3 field. Confocal laser microscopic analysis using PTZ-kindled mice illustrated that most SV2A was co-expressed with glutamic acid decarboxylase 67 in the cell bodies and dendrites of hilar interneurons. However, SV2A-immunoreactivity was negligibly observed in the hilar glutamatergic nerve terminals (mossy fibers) probed with the anti-vesicular glutamate transporter 1 antibody. The present study suggests that SV2A specifically regulates hilar GABAergic neurotransmission in the kindled hippocampus probably as a compensatory or prophylactic mechanism against kindling epileptogenesis.
进行了免疫组织化学研究，以分析戊四氮（PTZ）点燃后海马突触小泡蛋白 2A（SV2A）的表达变化。用亚惊厥剂量的 PTZ（40mg/kg，腹腔注射）重复治疗小鼠 15 天，逐渐增强了癫痫易感性，并在大多数检查的动物中引起了阵挛性惊厥。海马 SV2A 免疫反应的拓扑分析表明，SV2A 在齿状回的门区、CA3 场的透明层和 CA3 锥体神经元周围密集表达。PTZ 点燃特异性地增加了齿状回门区的 SV2A 表达，而不影响透明层或 CA3 场的锥体细胞层。使用 PTZ 点燃的小鼠进行共聚焦激光显微镜分析表明，大多数 SV2A 与谷氨酸脱羧酶 67 在门区中间神经元的胞体和树突中共表达。然而，在门区谷氨酸能神经末梢（苔藓纤维）用抗囊泡谷氨酸转运体 1 抗体探测时，几乎观察不到 SV2A 免疫反应性。本研究表明，SV2A 可能作为一种补偿或预防点燃性癫痫发生的机制，特异性地调节点燃海马中的门区 GABA 能神经传递。
