Neuroglycan C, a chondroitin sulfate proteoglycan, overcomes the abnormal behavior induced by administration of some drugs?

神经多糖C(NGC)是一种硫酸软骨素蛋白多糖，主要在大脑中表达。为了阐明NGC在脑发育中的作用，我们培育了三个品系的NGC基因突变小鼠，包括NGC基因敲除(NGC-KO)小鼠，它们完全缺乏NGC的所有剪接变体。已有研究表明，对某些精神药物的行为敏化与NGC基因表达的上调和下调有关。因此，我们利用旷场实验研究了几种精神刺激剂与NGC-KO小鼠行为的关系。不出所料，NGC-KO小鼠表现出与野生小鼠不同的行为。再加上在旷场实验中观察到NGC-KO小鼠的过度活动，NGC-KO小鼠可能被评估为注意缺陷/多动障碍(ADHD)的动物模型。为了阐明ADHD的发病机制，用双向凝胶电泳法检测了精神刺激剂甲基苯丙胺对NGC-KO和野生型小鼠大脑皮层蛋白质图谱的影响。发现了一种可能与甲基苯丙胺引起的多动有关的蛋白质。作为阐明NGC作用的另一种尝试，我们研究了结合蛋白，发现多营养素是一种NGC结合蛋白。

Neuroglycan C(NGC), a chondroitin sulfate proteoglycan, is predominantly expressed in the brain. To clarify the roles of NGC in the brain development, we generated three strains of NGC-gene mutant mice, including NGC-knockout(NGC-KO) mice that are completely deficient in all splice variants of NGC. It has been reported that the behavioral sensitization to some psychotropic drugs is associated with up-and down-regulation of NGC gene expression. So we have investigated the relationship of several psychostimulants and the behavior of NGC-KO mice using the open field test. As expected, NGC-KO mice showed different behavior compared with wild mice. Together with that hyperactivity was observed in NGC-KO mice in the open field test, NGC-KO mice may be evaluated as an animal model of attention-deficit/hyperactivity disorder(ADHD). To make the mechanism of ADHD clear, the changes of protein patterns in the cerebral cortex of NGC-KO and wild mice were examined using two-dimensional gel electrophoresis after the administration of methamphetamine, a psychostimulant. A protein which may be related to hyperactivity induced by methamphetamine was found. As another trial for clarifying the roles of NGC, we studied the binding proteins and found that pleiotrophin was a NGC-binding protein.