Neuronal hyperexcitability and seizures are associated with changes in glial-neuronal interactions in the hippocampus of a mouse model of epilepsy with mental retardation
Neuronal hyperexcitability and seizures are associated with changes in glial-neuronal interactions in the hippocampus of a mouse model of epilepsy with mental retardation
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DOI：
10.1111/j.1471-4159.2010.07048.x
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发表时间：
2010-12-01
影响因子：
4.7
通讯作者：
Mennini, Tiziana
中科院分区：
文献类型：
--
作者：
Melo, Torun;Bigini, Paolo;Mennini, Tiziana
研究了22周龄运动神经元变性（mnd）小鼠海马兴奋性和代谢性胶质神经元相互作用。与对照组小鼠相比，精神病小鼠在海马体中产生了自发的尖峰，更容易受到盐酸盐引起的癫痫发作的影响。c-Fos阳性核的选择性增加证实了海马神经元的高兴奋性。神经活性氨基酸和n -乙酰天冬氨酸含量不变表明，即使在没有明显海马神经退行性变的情况下，心智小鼠海马中也观察到胶质细胞激活和促炎性细胞因子的过度表达。其他氨基酸的浓度，包括GABA和谷氨酸，也没有变化。然而，体外13c磁共振波谱显示，同时注射[1- 13c]葡萄糖和[1,2- 13c]醋酸，然后斩首后，海马星形细胞前体[1,2- 13c]GABA的形成减少，谷氨酰胺衍生的[4,5- 13c]谷氨酸明显减少。我们认为星形胶质细胞功能障碍在其发病过程中起主要作用，心智小鼠对研究进行性癫痫伴智力低下的早期发病机制具有重要价值。
P>Hippocampal excitability and the metabolic glial-neuronal interactions were investigated in 22-week-old mice with motor neuron degeneration (mnd), a model of progressive epilepsy with mental retardation. Mnd mice developed spontaneous spikes in the hippocampus and were more susceptible to kainate-induced seizures compared with control mice. Neuronal hyperexcitability in their hippocampus was confirmed by the selective increase of c-Fos positive nuclei. Glial activation and pro-inflammatory cytokines over-expression were observed in the hippocampus of mnd mice, even in the absence of marked hippocampal neurodegeneration, as suggested by unchanged amounts of neuroactive amino acids and N-acetyl aspartate. Concentration of other amino acids, including GABA and glutamate, was not changed as well. However, ex vivo13C magnetic resonance spectroscopy, after simultaneous injection of [1-13C]glucose and [1,2-13C]acetate, followed by decapitation, showed decreased [1,2-13C]GABA formation from hippocampal astrocytic precursors and a marked reduction in [4,5-13C]glutamate derived from glutamine. We suggest that astrocyte dysfunction plays a primary role in the pathology and that mnd mice are of value to investigate early pathogenetic mechanism of progressive epilepsy with mental retardation.