Université de Bordeaux, INCIA, UMR 5287, Bordeaux, France.
CNRS, INCIA, UMR 5287, Bordeaux, France.
CNS Neurosci Ther. 2018 Apr;24(4):292-300. doi: 10.1111/cns.12826. Epub 2018 Feb 21.
Hereditary Huntington's disease (HD) is characterized by cell dysfunction and death in the brain, leading to progressive cognitive, psychiatric, and motor impairments. Despite molecular and cellular descriptions of the effects of the HD mutation, no effective pharmacological treatment is yet available. In addition to well-established alterations of glutamatergic and dopaminergic neurotransmitter systems, it is becoming clear that the GABAergic systems are also impaired in HD. GABA is the major inhibitory neurotransmitter in the brain, and GABAergic neurotransmission has been postulated to be modified in many neurological and psychiatric diseases. In addition, GABAergic neurotransmission is the target of many drugs that are in wide clinical use. Here, we summarize data demonstrating the occurrence of alterations of GABAergic markers in the brain of HD carriers as well as in rodent models of the disease. In particular, we pinpoint HD-related changes in the expression of GABA receptors (GABA Rs). On the basis that a novel GABA pharmacology of GABA Rs established with more selective drugs is emerging, we argue that clinical treatments acting specifically on GABAergic neurotransmission may be an appropriate strategy for improving symptoms linked to the HD mutation.
遗传性亨廷顿病 (HD) 的特征是大脑中的细胞功能障碍和死亡，导致进行性认知、精神和运动障碍。尽管对 HD 突变的分子和细胞效应已有描述，但仍没有有效的药物治疗方法。除了谷氨酸能和多巴胺能神经递质系统的明确改变外，GABA 能系统在 HD 中也受到损害这一点变得越来越清楚。GABA 是大脑中的主要抑制性神经递质，GABA 能神经传递被假定在许多神经和精神疾病中发生改变。此外，GABA 能神经传递是许多广泛应用于临床的药物的作用靶点。在这里，我们总结了表明 HD 携带者大脑中以及疾病啮齿动物模型中 GABA 能标记物发生改变的数据。特别是，我们指出了 GABA 受体 (GABA Rs) 表达方面与 HD 相关的变化。基于使用更具选择性药物建立的 GABA Rs 的新型 GABA 药理学正在出现，我们认为专门针对 GABA 能神经传递的临床治疗可能是改善与 HD 突变相关症状的合适策略。
