Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Ann Clin Transl Neurol. 2021 Jan;8(1):224-237. doi: 10.1002/acn3.51274. Epub 2020 Dec 21.
Dopamine D2-like receptors - mainly dopamine D2 receptors (D2R) and dopamine D3 receptors (D3R) - are believed to be greatly involved in the pathology of Parkinson disease (PD) progression. However, these receptors have not been precisely examined in PD patients. Our aim was to quantitatively calculate the exact densities of dopamine D1 receptors (D1R), D2R, and D3R in control, Alzheimer disease (AD), and Lewy body disease (LBD) patients (including PD, Dementia with Lewy bodies, and Parkinson disease dementia); and analyze the relationship between dopamine receptors and clinical PD manifestations.
We analyzed the densities of D1R, D2R, and D3R in the striatum and substantia nigra (SN) using a novel quantitative autoradiography procedure previously developed by our group. We also examined the expression of D2R and D3R mRNA in the striatum by in situ hybridization.
The results showed that although no differences of striatal D1R were found among all groups; D2R was significantly decreased in the striatum of PD patients when compared with control and AD patients. Some clinical manifestations: age of onset, PD stage, dopamine responsiveness, and survival time after onset; showed a better correlation with striatal D1R + D3R densities combined compared to D1R or D3R alone.
There is a possibility that we may infer the results in diagnosis, treatment, and prognosis of PD by detecting D1R + D3R as opposed to using dopamine D1 or D3 receptors alone. This is especially true for elderly patients with low D2R expression as is common in this disease.
多巴胺 D2 样受体 - 主要是多巴胺 D2 受体(D2R)和多巴胺 D3 受体(D3R) - 被认为与帕金森病(PD)进展的病理学密切相关。然而,这些受体在 PD 患者中尚未得到精确检查。我们的目的是定量计算对照、阿尔茨海默病(AD)和路易体病(LBD)患者(包括 PD、路易体痴呆和帕金森病痴呆)中多巴胺 D1 受体(D1R)、D2R 和 D3R 的准确密度;并分析多巴胺受体与临床 PD 表现之间的关系。
我们使用我们小组之前开发的一种新的定量放射自显影程序分析纹状体和黑质(SN)中 D1R、D2R 和 D3R 的密度。我们还通过原位杂交检查了纹状体中 D2R 和 D3R mRNA 的表达。
结果表明,尽管各组之间纹状体 D1R 没有差异;与对照组和 AD 患者相比,PD 患者纹状体中的 D2R 明显减少。一些临床表现:发病年龄、PD 分期、多巴胺反应性和发病后生存时间;与纹状体 D1R + D3R 密度的组合相比,与 D1R 或 D3R 单独相比,具有更好的相关性。
通过检测 D1R + D3R 而不是单独使用多巴胺 D1 或 D3 受体,有可能推断出 PD 的诊断、治疗和预后结果。对于在这种疾病中常见的低 D2R 表达的老年患者来说尤其如此。