Tocco G, Bi X, Vician L, Lim I K, Herschman H, Baudry M
Neuroscience Program, University of Southern California, Los Angeles, 90089-2520, USA.
Brain Res Mol Brain Res. 1996 Sep 1;40(2):229-39. doi: 10.1016/0169-328x(96)00055-1.
The synaptotagmins together with other vesicle proteins are thought to be essential for the docking and/or fusion of synaptic vesicles with the plasma membrane that occurs following depolarization and calcium influx in presynatic terminals. Syt4, the fourth identified member of the synaptotagmin family, is inducible in PC12 cells by depolarization and secretagogues, and in limbic regions of the adult rat brain by kainic acid-induced seizures. In the present study, we examined the time course of the seizure-induced changes in the expression of Syt4 and Syt1, both in adult animals and during the postnatal period. Syt4 was transiently induced in several structures of the adult rat brain following seizure activity with peak inductions between 4 and 8 h and overal return to control values by 30 h. No induction was observed following seizure activity in 7-day-old animals. The brain regions most sensitive to increased induction were, in decreasing order of sensitivity, hippocampal pyramidal cells dentate granule cells and piriform cortex pyramidal cells. The brain areas showing the greatest Syt4 stimulation in adults were also the areas in which Syt4 was induced by seizures earlier in development. In contrast, Syt1 mRNA was depressed in adult brains following seizure activity, particularly in the dentate granule cells. Our results suggest that the differential regulation of different synaptotagmin genes following excessive neuronal activity might participate in rapid adaptation of subsequent transmitter release.
突触结合蛋白与其他囊泡蛋白一起，被认为对于突触前终末去极化和钙内流后发生的突触囊泡与质膜的对接和/或融合至关重要。Syt4是突触结合蛋白家族中第四个被鉴定的成员，可通过去极化和促分泌剂在PC12细胞中诱导表达，也可通过 kainic 酸诱导的癫痫发作在成年大鼠脑的边缘区域诱导表达。在本研究中，我们研究了癫痫发作诱导的Syt4和Syt1表达变化的时间进程，包括成年动物和出生后时期。癫痫发作后，成年大鼠脑的几个结构中Syt4被短暂诱导，诱导峰值出现在4至8小时之间，到30小时总体恢复到对照值。7日龄动物癫痫发作后未观察到诱导现象。对诱导增加最敏感的脑区，按敏感性从高到低依次为海马锥体细胞、齿状颗粒细胞和梨状皮质锥体细胞。在成年动物中显示出最大Syt4刺激的脑区，也是在发育早期癫痫发作诱导Syt4的区域。相比之下，癫痫发作后成年大脑中Syt1 mRNA表达降低，尤其是在齿状颗粒细胞中。我们的结果表明，神经元活动过度后不同突触结合蛋白基因的差异调节可能参与随后递质释放的快速适应。
