Mori Fumiaki, Nishie Makoto, Kakita Akiyoshi, Yoshimoto Makoto, Takahashi Hitoshi, Wakabayashi Koichi
Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, Japan.
J Neuropathol Exp Neurol. 2006 Aug;65(8):808-15. doi: 10.1097/01.jnen.0000230520.47768.1a.
The histologic hallmark of Parkinson disease (PD) is loss of pigmented neurons in the substantia nigra (SN) and locus ceruleus (LC) with accumulation of alpha-synuclein (alphaS). It has been reported that tyrosine hydroxylase (TH)-negative pigmented neurons are present in these nuclei of patients with PD. However, the relationship between TH immunoreactivity and alphaS accumulation remains uncertain. We immunohistochemically examined the SN and LC from patients with PD (n = 10) and control subjects (n = 7). A correlation study indicated a close relationship among decreased TH immunoreactivity, alphaS accumulation, and neuronal loss. In addition, 10% of pigmented neurons in the SN and 54.9% of those in the LC contained abnormal alphaS aggregates. Moreover, 82.3% of pigmented neurons bearing alphaS aggregates in the SN and 39.2% of those in the LC lacked TH immunoreactivity, suggesting that pigmented neurons in the SN have a greater tendency to lack TH activity than those in the LC. Recent studies have shown that this decrease of TH activity leads to a decrease of cytotoxic substances and that decreased dopamine synthesis leads to a reduction of cytotoxic alphaS oligomers. Therefore, the decrease of TH immunoreactivity in pigmented neurons demonstrated here can be considered to represent a cytoprotective mechanism in PD.
帕金森病（PD）的组织学特征是黑质（SN）和蓝斑（LC）中色素神经元丧失以及α-突触核蛋白（αS）的积累。据报道，PD患者的这些核中存在酪氨酸羟化酶（TH）阴性的色素神经元。然而，TH免疫反应性与αS积累之间的关系仍不确定。我们对10例PD患者和7例对照者的SN和LC进行了免疫组织化学检查。一项相关性研究表明，TH免疫反应性降低、αS积累和神经元丧失之间存在密切关系。此外，SN中10%的色素神经元和LC中54.9%的色素神经元含有异常的αS聚集体。此外，SN中82.3%带有αS聚集体的色素神经元和LC中39.2%的此类神经元缺乏TH免疫反应性，这表明SN中的色素神经元比LC中的色素神经元更倾向于缺乏TH活性。最近的研究表明，TH活性的这种降低会导致细胞毒性物质减少，多巴胺合成减少会导致细胞毒性αS寡聚体减少。因此，此处显示的色素神经元中TH免疫反应性降低可被认为代表了PD中的一种细胞保护机制。
