Warren Naomi M, Piggott Margaret A, Greally Elizabeth, Lake Michelle, Lees Andrew J, Burn David J
Institute for Ageing and Heath, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
Mov Disord. 2007 Aug 15;22(11):1594-600. doi: 10.1002/mds.21573.
Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder. In contrast to Parkinson's disease (PD) and dementia with Lewy bodies (DLB), replacement therapy with dopaminergic and cholinergic agents in PSP has been disappointing. The neurochemical basis for this is unclear. Our objective was to measure dopaminergic and cholinergic receptors in the basal ganglia of PSP and control brains. We measured, autoradiographically, dopaminergic (dopamine transporter, 125I PE2I and dopamine D2 receptors, 125I epidepride) and cholinergic (nicotinic alpha4beta2 receptors, 125I 5IA85380 and muscarinic M1 receptors, 3H pirenzepine) parameters in the striatum and pallidum of pathologically confirmed PSP cases (n=15) and controls (n=32). In PSP, there was a marked loss of dopamine transporter and nicotinic alpha4beta2 binding in the striatum and pallidum, consistent with loss of nigrostriatal neurones. Striatal D2 receptors were increased in the caudate and muscarinic M1 receptors were unchanged compared with controls. These results do not account for the poor response to dopaminergic and cholinergic replacement therapies in PSP, and suggest relative preservation of postsynaptic striatal projection neurones bearing D2/M1 receptors.
进行性核上性麻痹（PSP）是一种进行性神经退行性疾病。与帕金森病（PD）和路易体痴呆（DLB）不同，PSP中使用多巴胺能和胆碱能药物进行替代治疗的效果并不理想。其神经化学基础尚不清楚。我们的目的是测量PSP患者和对照者大脑基底神经节中的多巴胺能和胆碱能受体。我们通过放射自显影法测量了病理确诊的PSP病例（n = 15）和对照者（n = 32）纹状体和苍白球中的多巴胺能（多巴胺转运体，125I PE2I和多巴胺D2受体，125I表哌立登）和胆碱能（烟碱α4β2受体，125I 5IA85380和毒蕈碱M1受体，3H哌仑西平）参数。在PSP中，纹状体和苍白球中的多巴胺转运体和烟碱α4β2结合显著减少，这与黑质纹状体神经元的丧失一致。与对照组相比，尾状核中的纹状体D2受体增加，毒蕈碱M1受体未发生变化。这些结果无法解释PSP对多巴胺能和胆碱能替代疗法反应不佳的原因，并提示携带D2/M1受体的突触后纹状体投射神经元相对保留。
