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首页> 外文期刊>Journal of Neurophysiology >Altered cortical glutamate receptor function in the R6/2 model of Huntington's disease.
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Altered cortical glutamate receptor function in the R6/2 model of Huntington's disease.

机译：亨廷顿舞蹈病的R6 / 2模型中皮质谷氨酸受体功能的改变。

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Alterations in pyramidal neurons from the sensorimotor cortex may be responsible for some of the cognitive and motor symptoms of Huntington's disease (HD). The present experiments used R6/2 transgenic mice that express exon 1 of the human HD gene with an expanded number of CAG repeats. We characterized alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) currents and their modulation by cyclothiazide (CTZ) as well as N-methyl-D-aspartate (NMDA) currents and their Mg2+ sensitivity in acutely dissociated cortical pyramidal neurons in R6/2 transgenic and wild-type (WT) mice at 21 days (before overt symptoms), 40 days (when symptoms begin), and 80 days (fully symptomatic). AMPA currents, alone or in the presence of CTZ, were smaller in 21- and 40-day-old R6/2 groups compared with WT mice. In R6/2 mice, more neurons displayed desensitizing AMPA currents in the presence of CTZ, indicating increased expression of "flop" splice variants, whereas the majority of WT cells expressed the "flip" variantsof AMPA receptor subunits. NMDA peak currents also were smaller in R6/2 pyramidal neurons at 21 days. At 40 days, NMDA currents were similar in WT and R6/2 mice but Mg2+ sensitivity was greater in R6/2 mice, resulting in smaller NMDA currents in the presence of Mg2+. Differences in AMPA and NMDA currents between WT and R6/2 cells were no longer detected at 80 days. Our findings indicate that currents induced by glutamate receptor agonists are decreased in isolated cortical pyramidal neurons from R6/2 mice and that this decrease occurs early. Altered glutamate receptor function could contribute to changes in cortical output and may underlie some of the cognitive and motor impairments in this animal model of HD.
机译：感觉运动皮层锥体神经元的改变可能是亨廷顿舞蹈病（HD）的一些认知和运动症状的原因。本实验使用R6 / 2转基因小鼠，该小鼠表达人类HD基因的外显子1，并带有大量的CAG重复序列。我们表征了α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）电流及其对环噻嗪（CTZ）和N-甲基-D-天冬氨酸（NMDA）电流的调制及其对Mg2 +的敏感性。在第21天（明显症状出现之前），40天（症状出现时）和80天（完全有症状）时，R6 / 2转基因和野生型（WT）小鼠的皮质锥体神经元解离。与WT小鼠相比，在21天和40天大的R6 / 2组中，单独或存在CTZ时，AMPA电流较小。在R6 / 2小鼠中，更多的神经元在存在CTZ的情况下显示出脱敏的AMPA电流，表明“翻转”剪接变体的表达增加，而大多数WT细胞表达了AMPA受体亚基的“翻转”变体。在21天时，R6 / 2锥体神经元的NMDA峰值电流也较小。在第40天时，WT和R6 / 2小鼠的NMDA电流相似，但R6 / 2小鼠的Mg2 +敏感性更高，导致存在Mg2 +时NMDA电流更小。在80天时，不再检测到WT和R6 / 2细胞之间的AMPA和NMDA电流差异。我们的发现表明，谷氨酸受体激动剂诱导的电流在R6 / 2小鼠的分离的皮质锥体神经元中减少，并且这种减少发生得较早。谷氨酸受体功能的改变可能有助于皮质输出的变化，并且可能是这种HD动物模型中某些认知和运动障碍的基础。

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