Kalk N J, Guo Q, Owen D, Cherian R, Erritzoe D, Gilmour A, Ribeiro A S, McGonigle J, Waldman A, Matthews P, Cavanagh J, McInnes I, Dar K, Gunn R, Rabiner E A, Lingford-Hughes A R
National Addictions Centre, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
Neuroimaging Department, Kings College London, London, UK.
Transl Psychiatry. 2017 Jan 10;7(1):e996. doi: 10.1038/tp.2016.264.
Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [C]PBR28. Regional volumes of distribution (V) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [C]PBR28 V in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in V in other ROIs. Hippocampal [C]PBR28 V was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [C]PBR28 V, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.
反复戒酒在临床上与进行性认知障碍相关。在酒精戒断的临床前模型中发生的小胶质细胞激活与学习缺陷有关。我们使用[C]PBR28正电子发射断层扫描（PET）研究了近期戒酒的酒精依赖患者（ADP）中是否存在小胶质细胞激活，[C]PBR28对在激活的小胶质细胞和星形胶质细胞中高表达的18kDa转位蛋白（TSPO）具有选择性。我们研究了小胶质细胞激活与认知表现之间的关系。对20名健康对照（HC）受试者（45±13岁；男：女为14：6）和9名ADP（45±6岁，男：女为9：0）进行了评估。在注射331±15MBq[C]PBR28后90分钟采集动态PET数据。使用具有代谢物校正动脉血浆输入函数的双组织隔室模型估计先验确定的感兴趣区域（ROI）的区域分布体积（V）。ADP的海马中[C]PBR28 V降低了约20%（F(1,24) 5.694；P=0.025），但其他ROI中的V没有差异。在HC和ADP的联合组中，海马[C]PBR28 V与言语记忆表现呈正相关（r=0.720，P<0.001），这种效应仅在HC中可见（r=0.738；P=0.001），而在ADP中未见。我们没有发现如临床前所见的ADP中小胶质细胞激活增加的证据。相反，我们的研究结果表明胶质细胞密度较低或激活状态改变，TSPO表达较低。言语记忆与[C]PBR28 V之间的相关性增加了胶质细胞功能异常可能导致ADP认知障碍的可能性。
