Microglial activation correlates with severity in Huntington disease - A clinical and PET study
Microglial activation correlates with severity in Huntington disease - A clinical and PET study
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DOI：
10.1212/01.wnl.0000222734.56412.17
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发表时间：
2006-06-13
期刊：
影响因子：
9.9
通讯作者：
Piccini, P.
中科院分区：
文献类型：
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作者：
Pavese, N.;Gerhard, A.;Piccini, P.
背景：亨廷顿病（HD）以携带纹状体gaba能神经元的中棘多巴胺受体进行性死亡为特征。此外，最近在死后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释放神经毒性细胞因子，这些可能有助于病理过程。方法：为了评估体内小胶质细胞激活在HD中的作用，作者使用[C-11](R)-PK11195 PET（一种小胶质细胞激活标记物）和[C-11] raclopride PET（一种多巴胺D2受体结合和纹状体gaba能细胞功能标记物）研究了疾病不同阶段的患者。结果：在HD患者中，纹状体[C-11](R)-PK11195结合显著增加，纹状体[C-11] raclopride结合降低，统一亨廷顿病评定量表评分降低，患者CAG指数降低，与疾病严重程度显著相关。同时还检测到包括前额皮质和前扣带在内的皮质区域的小胶质细胞激活显著增加。结论：这些[C-11](R)-PK11195 PET结果表明，小胶质细胞激活水平与亨廷顿病（HD）的严重程度相关。他们支持了小胶质细胞参与HD患者持续的神经元变性的观点，并表明[C-11](R)-PK11195 PET在监测这种持续进展的遗传疾病中假定的神经保护剂的功效时提供了一个有价值的标记。
Background: 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. Methods: To evaluate in vivo the involvement of microglia activation in HD, the authors studied patients at different stages of the disease using [ C-11]( R)-PK11195 PET, a marker of microglia activation, and [ C-11] raclopride PET, a marker of dopamine D2 receptor binding and hence striatal GABAergic cell function. Results: In HD patients, a significant increase in striatal [ C-11]( R)-PK11195 binding was observed, which significantly correlated with disease severity as reflected by the striatal reduction in [ C-11] 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. Conclusions: These [ C-11]( R)-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 [ C-11]( R)-PK11195 PET provides a valuable marker when monitoring the efficacy of putative neuroprotecting agents in this relentlessly progressive genetic disorder.