Prince of Wales Medical Research Institute and University of New South Wales, Sydney, Australia.
Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S152-5. doi: 10.1016/S1353-8020(09)70804-1.
One of the most marked differences to be identified in Parkinson's disease is the change in activity of thalamic neurons in the motor circuits. Because dopamine replacement therapies largely alleviate these motor circuit abnormalities, it has been assumed that pathology in the basal ganglia is entirely responsible for the aberrant thalamic activity which then permeates the motor circuits. However, there is considerable evidence that pathology in the thalamus itself contributes to the abnormal neural activity characteristic of Parkinson's disease. In a series of studies examining the degree of degeneration in the thalamus, we have observed selective degeneration in the intralaminar thalamic nuclei in patients with levodopa-responsive Parkinson's disease. The nuclei involved are the caudal intralaminar nuclei (the centre-median/parafascicular complex), the parataenial, cucullar and central lateral nuclei. The centre-median/parafascicular complex provides important glutaminergic feedback from the thalamus to the putamen and is a pathway that is greatly enlarged in primates. There is 30-40% loss in this region of the thalamus in idiopathic Parkinson's disease, with non-parvalbumin-containing neurons degenerating the most (70% average loss). Our recent work suggests that the preservation of this pathway may contribute to dystonia in Parkinson's disease. The central lateral and cucullar thalamic nuclei degenerate 30-50%, while the parataenial nucleus sustains a 55% loss of neurons in association with significant alpha-synuclein deposition which correlates with disease duration. Damage to these regions appears to impact on cognition, awareness and perception. These studies suggest that direct thalamic pathology contributes to the symptoms of Parkinson's disease.
帕金森病中最显著的差异之一是运动回路中丘脑神经元活动的改变。由于多巴胺替代疗法在很大程度上缓解了这些运动回路异常，因此人们假设基底神经节的病理学完全负责异常的丘脑活动，而这种活动会渗透到运动回路中。然而，有相当多的证据表明，丘脑本身的病理学也导致了帕金森病特征性的异常神经活动。在一系列研究中，我们观察到左旋多巴反应性帕金森病患者的丘脑内板核选择性退化。涉及的核团包括尾侧内板核（中央-median/旁正中复合核）、旁缰核、小脑和中央外侧核。中央-median/旁正中复合核提供了来自丘脑到壳核的重要谷氨酸能反馈，是灵长类动物中被极大放大的通路。在特发性帕金森病中，该丘脑区域有 30-40%的损失，非副钙蛋白神经元退化最严重（平均损失 70%）。我们最近的工作表明，该通路的保留可能有助于帕金森病的肌张力障碍。中央外侧和小脑丘脑核退化 30-50%，而旁缰核则伴有显著的α-突触核蛋白沉积，神经元损失 55%，与疾病持续时间相关。这些区域的损伤似乎会影响认知、意识和感知。这些研究表明，直接的丘脑病理学导致了帕金森病的症状。
