Persistent defect in transmitter release and synapsin phosphorylation in cerebral cortex after transient moderate ischemic injury
Persistent defect in transmitter release and synapsin phosphorylation in cerebral cortex after transient moderate ischemic injury
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DOI：
10.1161/01.str.0000013708.54623.de
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发表时间：
2002-05-01
期刊：
影响因子：
8.3
通讯作者：
Dalkara, T
中科院分区：
文献类型：
--
作者：
Bolay, H;Gürsoy-Özdemir, Y;Dalkara, T
背景和目的--突触传递非常容易受到代谢干扰的影响。然而，暂时性代谢紊乱对突触的长期影响尚不清楚。我们研究了短暂性中度脑缺血后大鼠半暗带皮质神经元突触传递和突触前蛋白磷酸化的长期变化。再灌流后，在细胞内和细胞外原位记录梗死区神经元的电活动。用免疫组织化学方法检测突触素-I和酪氨酸残基的磷酸化。结果：再灌流后1~3h，半影区神经元无突触后电位。然而，这些细胞能够产生动作电位并对谷氨酸做出反应，这表明突触后兴奋性被保留，但突触传递因突触前缺陷而受阻。缺血存活的梗死区神经元在再循环24小时后，突触传递仍然受到抑制。再灌流72小时后，突触素-I、突触素和突触素的免疫反应强度无明显变化。然而，突触素-I的磷酸化显著降低，而磷酸酪氨酸免疫反应性增加，提示突触蛋白-I的磷酸化存在选择性缺陷。结论--这些数据表明，短暂性中度脑损伤后突触传递可能受到永久性损害。由于突触后兴奋性被保留，传递失败很可能是由突触前机制引起的，其中之一可能是突触前蛋白的磷酸化受损。
Background and Purpose-Synaptic transmission is highly vulnerable to metabolic perturbations. However, the long-term consequences of transient metabolic perturbations on synapses are not clear. We studied the long-lasting changes in synaptic transmission and phosphorylation of presynaptic proteins in penumbral cortical neurons after transient moderate ischemia.Methods-Rats were subjected to 1 hour of middle cerebral artery occlusion. After reperfusion, electric activity of neurons in the peri-infarct region was recorded intracellularly and extracellularly in situ. Phosphorylation of synapsin-I and tyrosine residues was studied by immunohistochemistry.Results-Neurons in the penumbra displayed no postsynaptic potentials 1 to 3 hours after recirculation. However, these cells were able to generate action potentials and were responsive to glutamate, suggesting that postsynaptic excitability was preserved but the synaptic transmission was blocked because of a presynaptic defect. The synaptic transmission was still depressed 24 hours after recirculation in neurons in the peri-infarct area that survived ischemia. The amount of immunoreactive synapsin-I, synaptophysin, and synaptotagmin was not appreciably changed for 72 hours after reperfusion. However, phosphorylation of synapsin-I was significantly decreased, whereas phosphotyrosine immunoreactivity was increased, suggesting a selective defect in synapsin-I phosphorylation.Conclusions-These data demonstrate that synaptic transmission may be permanently impaired after transient moderate brain injury. Since postsynaptic excitability is preserved, the transmission failure is likely to be caused by presynaptic mechanisms, one of which may be impaired phosphorylation of presynaptic proteins.