Department of Neurology, Johns Hopkins University, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA.
Sleep Med. 2009 Dec;10(10):1155-7. doi: 10.1016/j.sleep.2009.01.006. Epub 2009 Mar 23.
Although the positive clinical benefits of levodopa have fostered the concept of an abnormality in the dopaminergic system in Restless Legs Syndrome (RLS), research into the nigro-striatal (PET/SPECT studies) or tubero-infundibular (i.e., prolactin secretion) dopaminergic pathways has shown limited positive results. Some research groups have focused on the A11 dopaminergic system in the hypothalamus as this is the primary source of descending dopaminergic input into the spinal cord, an area of the nervous system believed by some investigators to be involved in RLS symptom development. Some investigators have now proposed lesioning or toxin-inhibiting the A11 system as a model of RLS, even though there has been no clear clinical or autopsy data to suggest that RLS is a neurodegenerative disorder. In this study, the A11 cell bodies were identified in 6 RLS and 6 aged-matched control autopsy cases. Cells were stained for tyrosine hydroxylase (TH), and stereological measure of the individual TH (+) cell volume was made. Regional assessment of gliosis as assessed by immunostaining for glial fibrillary acidic protein (GFAP) was made in the surrounding tissue. General histological staining was also performed on the tissue. This study found no significant difference between RLS or control cases on any measure used: TH (+) cell volume, fractional GFAP staining, or general histological examination. Nor was there histological indication of any significant inflammation or concurrent ongoing pathology in these RLS cases. The findings do not support the concept of dramatic cell loss or of a neurodegenerative process in the A11 hypothalamic region of patients with RLS. However, that does not exclude the possibility that the A11 system is involved in RLS symptoms. Changes at the cellular level in dopaminergic metabolism or at the distal synapse with changes in receptors or transporters were not evaluated in this study.
虽然左旋多巴的积极临床益处促进了不宁腿综合征（RLS）中多巴胺能系统异常的概念，但对黑质纹状体（PET/SPECT 研究）或结节漏斗（即催乳素分泌）多巴胺能途径的研究显示出有限的阳性结果。一些研究小组专注于下丘脑的 A11 多巴胺能系统，因为这是下行多巴胺能传入脊髓的主要来源，一些研究人员认为该神经系统区域与 RLS 症状的发展有关。一些研究人员现在提出了损伤或毒素抑制 A11 系统作为 RLS 的模型，尽管没有明确的临床或尸检数据表明 RLS 是一种神经退行性疾病。在这项研究中，在 6 例 RLS 和 6 例年龄匹配的对照尸检病例中确定了 A11 细胞体。细胞用酪氨酸羟化酶（TH）染色，并对单个 TH（+）细胞体积进行立体学测量。用胶质纤维酸性蛋白（GFAP）免疫染色评估周围组织的神经胶质增生程度。还对组织进行了一般组织学染色。在任何使用的测量方法上，RLS 或对照病例之间均无显著差异：TH（+）细胞体积、GFAP 染色的分数或一般组织学检查。在这些 RLS 病例中也没有组织学迹象表明存在任何明显的炎症或并发进行性病变。这些发现不支持 RLS 患者 A11 下丘脑区域存在明显细胞丢失或神经退行性过程的概念。但是，这并不能排除 A11 系统参与 RLS 症状的可能性。在这项研究中没有评估多巴胺能代谢或在远端突触处的细胞水平变化，例如受体或转运体的变化。
