Brooks Daniel, Halliday Glenda M
Prince of Wales Medical Research Institute and the University of New South Wales, Sydney, Australia.
Brain Res Bull. 2009 Feb 16;78(2-3):97-104. doi: 10.1016/j.brainresbull.2008.08.014. Epub 2008 Sep 18.
Although the intralaminar thalamus is a target of alpha-synuclein pathology in Parkinson's disease, the degree of neuronal loss in Lewy body diseases has not been assessed. We have used unbiased stereological techniques to quantify neuronal loss in intralaminar thalamic nuclei concentrating alpha-synuclein pathology (the anterodorsal, cucullar, parataenial, paraventricular, central medial, central lateral and centre-median/parafascicular complex) in different clinical forms of Lewy body disease (Parkinson's disease with and without dementia, and dementia with Lewy bodies, N=21) compared with controls (N=5). Associations were performed in the Lewy body cases between intralaminar cell loss and the main diagnostic clinical (parkinsonism, dementia, fluctuation in consciousness, and visual hallucinations) and pathological (Braak stage of Parkinson's disease) features of these diseases, as well as between cell loss and the scaled severity of the alpha-synuclein deposition within the intralaminar thalamus. As expected, significant alpha-synuclein accumulation occurred in the intralaminar thalamus in the cases with Lewy body disease. Pathology concentrated anteriorly and in the central lateral and paraventricular nuclei was related to the Braak stage of Parkinson's disease, ageing, and the presence of dementia. Across all types of Lewy body cases there was substantial atrophy and neuronal loss in the central lateral, cucullar and parataenial nuclei, and neuronal loss without atrophy in the centre-median/parafascicular complex. Cases with visual hallucinations showed a greater degree of atrophy of the cucullar nucleus, possibly due to amygdala denervation. The significant degeneration demonstrated in the intralaminar thalamus is likely to contribute to the movement and cognitive dysfunction observed in Lewy body disorders.
尽管丘脑板内核是帕金森病中α-突触核蛋白病理改变的靶点，但路易体病中神经元丢失的程度尚未得到评估。我们运用无偏倚的立体学技术，对路易体病不同临床类型（伴或不伴痴呆的帕金森病以及路易体痴呆，N = 21）中，集中有α-突触核蛋白病理改变的丘脑板内核（前背核、钩核、旁束旁核、室旁核、中央内侧核、中央外侧核以及中央中核/束旁复合体）的神经元丢失情况进行了量化，并与对照组（N = 5）进行比较。在路易体病病例中，对丘脑板内细胞丢失与这些疾病的主要诊断性临床特征（帕金森综合征、痴呆、意识波动以及视幻觉）和病理特征（帕金森病的Braak分期）之间进行了相关性分析，同时也分析了细胞丢失与丘脑板内核内α-突触核蛋白沉积的严重程度之间的相关性。正如预期的那样，路易体病病例中丘脑板内核出现了明显的α-突触核蛋白聚集。病理改变集中在前部以及中央外侧核和室旁核，这与帕金森病的Braak分期、年龄以及痴呆的存在有关。在所有类型的路易体病病例中，中央外侧核、钩核和旁束旁核均出现了显著萎缩和神经元丢失，而中央中核/束旁复合体则出现了无萎缩性的神经元丢失。有视幻觉的病例中，钩核萎缩程度更严重，这可能是由于杏仁核去神经支配所致。丘脑板内核中显示出的显著变性很可能导致了路易体病中出现的运动和认知功能障碍。
