Role of cerebral cortex in the neuropathology of Huntington's disease.
Role of cerebral cortex in the neuropathology of Huntington's disease.
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DOI：
10.3389/fncir.2013.00019
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发表时间：
2013
影响因子：
3.5
通讯作者：
Rebec GV
中科院分区：
文献类型：
--
作者：
Estrada-Sánchez AM;Rebec GV
亨廷顿蛋白的N-末端结构域中谷氨酰胺重复序列的扩增导致亨廷顿病（HD），这是一种以存在不自主运动、痴呆和精神障碍为特征的神经变性病症。对死后HD组织的评价表明，最显著的细胞损失发生在大脑皮层和纹状体、前脑区域，其中皮层锥体神经元（CPN）和纹状体中型棘神经元（MSN）受影响最大。从HD患者，特别是从HD的转基因小鼠模型中获得的后续证据表明，早在神经元死亡之前，CPNs和MSN之间的通信模式就变得功能障碍。事实上，转基因HD小鼠的电生理信号甚至在HD行为表型出现之前就发生了改变，这表明对纹状体的功能障碍性皮质输入为HD神经学体征的出现奠定了基础。此外，纹状体MSN通过多突触连接投射回皮层，从而进一步破坏皮层处理。因此，HD的有效治疗策略可能在于了解其使皮质纹状体系统失调的突触机制。在这里，我们回顾文献评估分子，形态学和生理学的改变，大脑皮层，大脑回路控制运动行为的关键组成部分，因为它们发生在患者和转基因HD模型。
An expansion of glutamine repeats in the N-terminal domain of the huntingtin protein leads to Huntington's disease (HD), a neurodegenerative condition characterized by the presence of involuntary movements, dementia, and psychiatric disturbances. Evaluation of postmortem HD tissue indicates that the most prominent cell loss occurs in cerebral cortex and striatum, forebrain regions in which cortical pyramidal neurons (CPNs) and striatal medium spiny neurons (MSNs) are the most affected. Subsequent evidence obtained from HD patients and especially from transgenic mouse models of HD indicates that long before neuronal death, patterns of communication between CPNs and MSNs become dysfunctional. In fact, electrophysiological signaling in transgenic HD mice is altered even before the appearance of the HD behavioral phenotype, suggesting that dysfunctional cortical input to the striatum sets the stage for the emergence of HD neurological signs. Striatal MSNs, moreover, project back to cortex via multi-synaptic connections, allowing for even further disruptions in cortical processing. An effective therapeutic strategy for HD, therefore, may lie in understanding the synaptic mechanisms by which it dysregulates the corticostriatal system. Here, we review literature evaluating the molecular, morphological, and physiological alterations in the cerebral cortex, a key component of brain circuitry controlling motor behavior, as they occur in both patients and transgenic HD models.
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影响因子：
--
作者：
Hong SL;Barton SJ;Rebec GV
通讯作者：
Rebec GV
影响因子：
3.3
作者：
Beurrier, C.;Bonvento, G.;Gubellini, P.
通讯作者：
Gubellini, P.
DOI：
10.1073/pnas.1016190108
发表时间：
2011-05-31
影响因子：
11.1
作者：
Cayzac, Sebastien;Delcasso, Sebastien;Cho, Yoon H.
通讯作者：
Cho, Yoon H.
影响因子：
16.2
作者：
Espinosa JS;Stryker MP
通讯作者：
Stryker MP
DOI：
10.1523/jneurosci.0388-12.2012
发表时间：
2012-05-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cepeda-Prado E;Popp S;Khan U;Stefanov D;Rodríguez J;Menalled LB;Dow-Edwards D;Small SA;Moreno H
通讯作者：
Moreno H