Single episode of neonatal seizures permanently alters glutamatergic synapses
Single episode of neonatal seizures permanently alters glutamatergic synapses
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DOI：
10.1002/ana.21071
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发表时间：
2007-05-01
影响因子：
11.2
通讯作者：
Benke, Timothy A.
中科院分区：
文献类型：
--
作者：
Cornejo, Brandon J.;Mesches, Michael H.;Benke, Timothy A.
目的：癫痫发作对认知功能改变的作用仍存在争议。我们验证了一种假说，即出生后第7天单次发生新生儿惊厥(SNS)会永久性损害成年(P60)大鼠的海马神经元依赖功能，这是因为突触水平的长期变化。方法：在P7皮下注射红藻氨酸诱导SNS。在P60时检测学习、记忆、苔藓纤维发芽、脊椎密度、海马神经元突触可塑性、谷氨酸受体表达和亚细胞分布。结果：三七总皂苷选择性地损害工作记忆，而不诱导苔藓纤维发芽，也不改变脊髓密度。三七总皂苷损伤CA1区海马长时程增强，增强长时程抑制。用来确定谷氨酸受体转运是否是记忆和突触可塑性改变的亚细胞分裂和交联法表明，SNS诱导了谷氨酸受体I亚单位膜池的选择性减少。SNS诱导的N-甲基-D-天冬氨酸受体2A总量减少，初级突触下支架PSD-95增加。解释：这些分子结果与SNS在突触水平引起的可塑性和记忆改变是一致的。我们的数据显示了SNS对认知的影响，并将记忆缺陷与谷氨酸能突触功能的特定变化联系在一起。
Objective: The contribution Of seizures to cognitive changes remains controversial. We tested the hypothesis that a single episode of neonatal seizures (sNS) on rat postnatal day (P) 7 permanently impairs hippocampal-dependent function in mature (P60) rats because of long-lasting changes at the synaptic level.Methods: sNS was induced with subcutaneously injected kainate on P7. Learning, memory, mossy fiber sprouting, spine density, hippocampal synaptic plasticity, and glutamate receptor expression and subcellular distribution were measured at P60.Results: sNS selectively impaired working memory in a hippocampal-dependent radial arm water-maze task without inducing mossy fiber sprouting or altering spine density. sNS impaired CA1 hippocampal long-term potentiation and enhanced long-term depression. Subcellular fractionation and cross-linking, used to determine whether glutamate receptor trafficking underlies the alterations of memory and synaptic plasticity, demonstrated that sNS induced a selective reduction in the membrane pool of glutamate receptor I subunits. sNS induced a decrease in the total amount of N-methyl-D-aspartate receptor 2A and an increase in the primary subsynaptic scaffold, PSD-95.Interpretation: These molecular consequences are consistent with the alterations in plasticity and memory caused by sNS at the synaptic level. Our data demonstrate the cognitive impact of sNS and associate memory deficits with specific alterations in glutamatergic synaptic function.