Depression of synaptic transmission by vascular endothelial growth factor in adult rat hippocampus and evidence for increased efficacy after chronic seizures
Depression of synaptic transmission by vascular endothelial growth factor in adult rat hippocampus and evidence for increased efficacy after chronic seizures
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DOI：
10.1523/jneurosci.2577-05.2005
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发表时间：
2005-09-28
影响因子：
5.3
通讯作者：
Scharfman, HE
中科院分区：
文献类型：
--
作者：
McCloskey, DP;Croll, SD;Scharfman, HE
除了对脉管系统的有效作用外，血管内皮生长因子 (VEGF) 对神经元和神经胶质细胞都有影响，最近的研究表明它可以起到神经保护作用。为了确定这种神经保护的潜在机制，将重组人 VEGF 应用于成年大鼠海马切片，并使用细胞外和细胞内记录来检查海马主要神经元的内在特性和突触反应。 CA1 区的初步研究表明，VEGF 显着降低了 Schaffer 侧支刺激引起的反应幅度，而不影响膜特性。当 CA3 锥体细胞和齿状回颗粒细胞的主要谷氨酸传入神经受到刺激时，类似的效应也会发生。由于癫痫发作后 VEGF 表达增加，因此还在反复自发性癫痫发作的大鼠中检查了 VEGF 的作用。 VEGF 减少了这些大鼠切片中的自发放电，但令人惊讶的是，对对照大鼠切片去抑制产生的癫痫样放电几乎没有影响。这些结果证明了 VEGF 对神经元活动的先前未知的影响，并且还证明了对癫痫大脑的显着效力。基于此，我们建议 VEGF 或 VEGF 相关靶点可以提供有用的终点来指导癫痫的新治疗策略。
In addition to its potent effects on vasculature, it has become clear that vascular endothelial growth factor ( VEGF) has effects on both neurons and glia, and recent studies suggest that it can be neuroprotective. To determine potential mechanisms underlying this neuroprotection, recombinant human VEGF was bath applied to adult rat hippocampal slices, and both extracellular and intracellular recordings were used to examine intrinsic properties and synaptic responses of hippocampal principal neurons. Initial studies in area CA1 showed that VEGF significantly reduced the amplitude of responses elicited by Schaffer collateral stimulation, without influencing membrane properties. Similar effects occurred in CA3 pyramidal cells and dentate gyrus granule cells when their major glutamatergic afferents were stimulated. Because VEGF expression is increased after seizures, effects of VEGF were also examined in rats with recurrent spontaneous seizures. VEGF reduced spontaneous discharges in slices from these rats but had surprisingly little effect on epileptiform discharges produced by disinhibition of slices from control rats. These results demonstrate a previously unknown effect of VEGF on neuronal activity and also demonstrate a remarkable potency in the epileptic brain. Based on this, we suggest that VEGF or VEGF-related targets could provide useful endpoints to direct novel therapeutic strategies for epilepsy.