Corticostriatal Dysfunction in Huntington's Disease: The Basics.
Corticostriatal Dysfunction in Huntington's Disease: The Basics.
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DOI：
10.3389/fnhum.2016.00317
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发表时间：
2016
影响因子：
2.9
通讯作者：
Rebec GV
中科院分区：
文献类型：
--
作者：
Bunner KD;Rebec GV
基底神经节的主要输入，皮质纹状体通路，显示出亨廷顿氏病（HD）的一些最早的神经病理学迹象，亨廷顿氏病是一种遗传性神经退行性疾病，通常在中年发作，伴有认知、情绪和运动症状逐渐恶化。虽然有效的治疗方法仍然难以捉摸，但转基因动物模型的研究表明，在HD发病过程中，皮质纹状体神经元释放的兴奋性氨基酸谷氨酸（Glu）失调。在突触后受体和Glu转运蛋白水平上控制Glu传递的异常在通过下游回路的信息流丢失中起关键作用，这为HD行为表型奠定了基础。多巴胺（DA）是谷氨酸激活的关键调节剂，它的平行但不太明确的变化，确保了整个基底神经节神经元通信的进一步缺陷。继续分析皮质纹状体谷氨酸传递及其通过DA的调节，包括转基因模型中神经行为水平的分析，可能是追求HD治疗的有效策略。
The main input to the basal ganglia, the corticostriatal pathway, shows some of the earliest signs of neuropathology in Huntington’s disease (HD), an inherited neurodegenerative condition that typically strikes in mid-life with progressively deteriorating cognitive, emotional, and motor symptoms. Although an effective treatment remains elusive, research on transgenic animal models has implicated dysregulation of glutamate (Glu), the excitatory amino acid released by corticostriatal neurons, in HD onset. Abnormalities in the control of Glu transmission at the level of postsynaptic receptors and Glu transport proteins play a critical role in the loss of information flow through downstream circuits that set the stage for the HD behavioral phenotype. Parallel but less-well characterized changes in dopamine (DA), a key modulator of Glu activation, ensure further deficits in neuronal communication throughout the basal ganglia. Continued analysis of corticostriatal Glu transmission and its modulation by DA, including analysis at the neurobehavioral level in transgenic models, is likely to be an effective strategy in the pursuit of HD therapeutics.