Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia
Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia
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DOI：
10.1212/wnl.0b013e3181ad53e7
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发表时间：
2009-07-14
期刊：
影响因子：
9.9
通讯作者：
Low, P. A.
中科院分区：
文献类型：
--
作者：
Benarroch, E. E.;Schmeichel, A. M.;Low, P. A.
背景：实验研究表明腹侧导水管周围灰质（PAG）中的多巴胺能神经元参与清醒的维持。白天过度嗜睡 (EDS) 是多系统萎缩 (MSA) 和路易体痴呆 (DLB) 的常见表现，但尚未探讨这些神经元的参与情况。方法：我们试图确定 MSA 和 DLB 腹侧 PAG 中的多巴胺能神经元是否缺失。我们研究了尸检时获得的中脑，这些患者来自 12 名经神经病理学确诊的 MSA 患者（9 名男性，3 名女性，年龄 61 +/- 3 岁），12 名诊断为 DLB 和边缘或新皮质路易体病的患者（11 名男性，1 名女性，79 +/- 4 岁），以及 12 名对照者（7 名男性，5 名女性，年龄 67 +/- 4 岁）。对 50 微米切片进行酪氨酸羟化酶 (TH) 或 α-突触核蛋白免疫染色，并与硫堇共染色。使用体视学技术对整个腹侧 PAG 每 400 μm 进行一次细胞计数。结果：与对照中的估计细胞总数（21,488 +/- 8,324 个细胞）相比，MSA（11,727 +/- 5,984；p < 0.01）和 DLB（5,163 +/- 5,163 +/- 1,926； p < 0.001) 例。 DLB 中的细胞损失比 MSA 中更明显。 MSA 和 DLB 的腹侧 PAG 中均存在特征性的 α-突触核蛋白内含物。结论：在多系统萎缩和路易体痴呆中，假定的唤醒活性腹侧导水管周围灰质多巴胺能神经元缺失，这可能导致这些情况下白天过度嗜睡。神经病学(R)2009; 73：106-112
Background: Experimental studies indicate that dopaminergic neurons in the ventral periaqueductal gray matter (PAG) are involved in maintenance of wakefulness. Excessive daytime sleepiness (EDS) is a common manifestation of multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) but involvement of these neurons has not yet been explored.Methods: We sought to determine whether there is loss of dopaminergic neurons in the ventral PAG in MSA and DLB. We studied the midbrain obtained at autopsy from 12 patients (9 male, 3 female, age 61 +/- 3) with neuropathologically confirmed MSA, 12 patients (11 male, 1 female, age 79 +/- 4) with diagnosis of DLB and limbic or neocortical Lewy body disease, and 12 controls (7 male, 5 female, ages 67 +/- 4). Fifty-micron sections were immunostained for tyrosine hydroxylase (TH) or alpha-synuclein and costained with thionin. Cell counts were performed every 400 mu m throughout the ventral PAG using stereologic techniques.Results: Compared to the total estimated cell numbers in controls (21,488 +/- 8,324 cells), there was marked loss of TH neurons in the ventral PAG in both MSA (11,727 +/- 5,984; p < 0.01) and DLB (5,163 +/- 1,926; p < 0.001) cases. Cell loss was more marked in DLB than in MSA. There were characteristic alpha-synuclein inclusions in the ventral PAG in both MSA and DLB.Conclusions: There is loss of putative wake-active ventral periaqueductal gray matter dopaminergic neurons in both multiple system atrophy and dementia with Lewy bodies, which may contribute to excessive daytime sleepiness in these conditions. Neurology(R) 2009; 73: 106-112