难治性癫癎的诊断和治疗进展__培训课件.pptVIP

* SV2A的具体功能目前还不是很清楚。但是已有的动物学研究显示SV2A是维持正常神经信息传递所必须的，认为是突触小泡与突触前膜融合过程的调节器。有趣的是，大鼠研究显示在敲除SV2A 基因后，胎鼠的大脑和突触发育及结构都正常，但是出生后死亡率却非常高。这些大鼠出生后几周都有癫痫的发生。SV2A基因敲除后，通过减少突触小泡的释放同时降低了神经传递的抑制和兴奋性。 SV2A的具体功能还不是很清楚，目前存在如下假说： 1，传递运输ATP或钙离子； 2，突触小泡的调节器或参与突触小泡融合的其他蛋白； 3，推断SV2A可能参与由钙离子启动的突触小泡融合过程； 4，也可能糖分子与SV2A耦联组成神经递质与突触小泡结合； We do not know the exact function of SV2A. However, previous studies performed in animals lacking the gene for SV2A have demonstrated that SV2A is required for normal neurotransmission and is thought to be a modulator of vesicle fusion process (Crowder et al., 1999; Lopanstev and Bajjallieh, 2002). Interestingly, mice lacking the SV2A gene (SV2A knock-outs) show completely normal brain and synapse development and structure, but do exhibit a high mortality in the weeks after birth. Those mice that do survive develop severe post-natal seizures and die within weeks. SV2A knock-outs show both reduced inhibitory and excitatory neurotransmission that may be due to a reduction in the pool of readily releasable vesicles (Lopanstev Bajjallieh, 2002; Xu Bajjallieh, 2001) . While the function of the SV2A protein is not known, several hypotheses include: transport of ATP or calcium (Crowder et al., 1999), modulator of synaptotagmin or other proteins involved in vesicle fusion and tethering (Crowder et al., 1999), speculation that SV2A may participate in calcium’s triggering of vesicle fusion (Crowder et al., 1999) and possibility that sugars associated to SV2A may form a neurotransmitter binding matrix within the vesicle (Reigada, 2003). Crowder et al., Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A), PNAS, 96:15268-73, 1999 Lopanstev and Bajjallieh, Glutamatergic neurotransmission is altered in neocortical neurons from SV2 knockout mice, Soc Neurosci Abstract, 2002, 253.7 Reigada et al., Control of neurotransmitter release by an internal gel matrix in synaptic vesicles, PNAS, 100(6):3485-90, 2003 Xu and Bajjallieh, SV2 modulates t