Pavese N, Gerhard A, Tai Y F, Ho A K, Turkheimer F, Barker R A, Brooks D J, Piccini P
MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK.
Neurology. 2006 Jun 13;66(11):1638-43. doi: 10.1212/01.wnl.0000222734.56412.17.
Huntington disease (HD) is characterized by the progressive death of medium spiny dopamine receptor bearing striatal GABAergic neurons. In addition, microglial activation in the areas of neuronal loss has recently been described in postmortem studies. Activated microglia are known to release neurotoxic cytokines, and these may contribute to the pathologic process.
To evaluate in vivo the involvement of microglia activation in HD, the authors studied patients at different stages of the disease using (11)C-PK11195 PET, a marker of microglia activation, and [(11)C]raclopride PET, a marker of dopamine D2 receptor binding and hence striatal GABAergic cell function.
In HD patients, a significant increase in striatal (11)C-PK11195 binding was observed, which significantly correlated with disease severity as reflected by the striatal reduction in [(11)C]raclopride binding, the Unified Huntington's Disease Rating Scale score, and the patients' CAG index. Also detected were significant increases in microglia activation in cortical regions including prefrontal cortex and anterior cingulate.
These (11)C-PK11195 PET findings show that the level of microglial activation correlates with Huntington disease (HD) severity. They lend support to the view that microglia contribute to the ongoing neuronal degeneration in HD and indicate that (11)C-PK11195 PET provides a valuable marker when monitoring the efficacy of putative neuroprotecting agents in this relentlessly progressive genetic disorder.
亨廷顿舞蹈症（HD）的特征是含有中等棘突多巴胺受体的纹状体γ-氨基丁酸能神经元进行性死亡。此外，最近在尸检研究中描述了神经元丢失区域的小胶质细胞激活。已知活化的小胶质细胞会释放神经毒性细胞因子，这些细胞因子可能促成病理过程。
为了在体内评估小胶质细胞激活在HD中的作用，作者使用[（11）C]（R）-PK11195 PET（一种小胶质细胞激活标记物）和[（11）C]雷氯必利PET（一种多巴胺D2受体结合标记物，从而反映纹状体γ-氨基丁酸能细胞功能）对处于疾病不同阶段的患者进行了研究。
在HD患者中，观察到纹状体[（11）C]（R）-PK11195结合显著增加，这与疾病严重程度显著相关，疾病严重程度通过纹状体[（11）C]雷氯必利结合减少、统一亨廷顿舞蹈病评定量表评分以及患者的CAG指数来反映。还检测到包括前额叶皮质和前扣带回在内的皮质区域小胶质细胞激活显著增加。
这些[（11）C]（R）-PK11195 PET研究结果表明，小胶质细胞激活水平与亨廷顿舞蹈症（HD）严重程度相关。这些结果支持了小胶质细胞促成HD中持续神经元变性的观点，并表明在监测这种无情进展的遗传性疾病中假定神经保护剂的疗效时，[（11）C]（R）-PK11195 PET提供了一个有价值的标记物。
