In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence.
In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence.
复制标题
在酒精依赖性中，流动蛋白的体内成像，即活化的小胶质细胞的标志。
DOI：
10.1038/mp.2017.10
复制
发表时间：
2017-12
影响因子：
11
通讯作者：
Cosgrove KP
中科院分区：
文献类型：
--
作者：
Hillmer AT;Sandiego CM;Hannestad J;Angarita GA;Kumar A;McGovern EM;Huang Y;O'Connor KC;Carson RE;O'Malley SS;Cosgrove KP
神经炎症可能是酒精使用障碍的神经生物学的一个重要组成部分，但这种关系的确切性质还没有得到很好的理解。这项工作比较了酒精依赖受试者和对照组的大脑和外周免疫概况。在15名健康对照和15名酒精依赖受试者中，采用[11 C] PBR 28正电子发射断层扫描成像测量了脑内18-kDa转运蛋白（TSPO）的水平，TSPO是小胶质细胞活化和神经炎症的标志物。酒精依赖受试者在他们最后一次饮酒后1-4天（n=14）或24天（n=1）进行成像。部分容积校正的[11 C] PBR 28数据的线性混合模型显示酒精依赖的主要影响（p=0.034），对应于酒精依赖受试者中TSPO水平降低10%。在该组内，探索性分析发现海马和纹状体中的TSPO水平与酒精依赖严重程度呈负相关（p<0.035）。通过测量在存在和不存在脂多糖的情况下培养的单核细胞的细胞因子表达来评估受试者亚组中的外周免疫应答。酒精依赖受试者外周血单核细胞对脂多糖刺激的反应低于对照组的促炎细胞因子IL-6和IL-8。因此，与对照组相比，酒精依赖个体在脑中表现出较少的活化小胶质细胞和钝化的外周促炎反应。这些发现表明药物调节神经免疫系统作为酒精依赖的治疗剂的作用。
Neuroinflammation may be a critical component of the neurobiology of alcohol use disorders, yet the exact nature of this relationship is not well understood. This work compared the brain and peripheral immune profile of alcohol dependent subjects and controls. Brain levels of 18-kDa translocator protein (TSPO), a marker of microglial activation and neuroinflammation, were measured with [11C]PBR28 positron emission tomography imaging in 15 healthy controls and 15 alcohol dependent subjects. Alcohol dependent subjects were imaged 1-4 days (n=14) or 24 days (n=1) after their last drink. Linear mixed modeling of partial volume corrected [11C]PBR28 data revealed a main effect of alcohol dependence (p=0.034), corresponding to 10% lower TSPO levels in alcohol dependent subjects. Within this group, exploratory analyses found a negative association of TSPO levels in hippocampus and striatum with alcohol dependence severity (p<0.035). Peripheral immune response was assessed in a subset of subjects by measuring cytokine expression from monocytes cultured both in the presence and absence of lipopolysaccharide. Peripheral monocyte response to lipopolysaccharide stimulation was lower in alcohol dependent subjects compared to controls for the pro-inflammatory cytokines IL-6 and IL-8. Thus, alcohol dependent individuals exhibited less activated microglia in brain and a blunted peripheral pro-inflammatory response compared to controls. These findings suggest a role for pharmaceuticals tuning the neuroimmune system as therapeutics for alcohol dependence.
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DOI：
10.1016/j.pnpbp.2014.05.003
发表时间：
2014-10-03
影响因子：
5.6
作者：
Geil, Chelsea R.;Hayes, Dayna M.;McClain, Justin A.;Liput, Daniel J.;Marshall, S. Alex;Chen, Kevin Y.;Nixon, Kimberly
通讯作者：
Nixon, Kimberly
影响因子：
3.2
作者：
Coughlin JM;Wang Y;Ma S;Yue C;Kim PK;Adams AV;Roosa HV;Gage KL;Stathis M;Rais R;Rojas C;McGlothan JL;Watkins CC;Sacktor N;Guilarte TR;Zhou Y;Sawa A;Slusher BS;Caffo B;Kassiou M;Endres CJ;Pomper MG
通讯作者：
Pomper MG
影响因子：
10.6
作者：
Crews, Fulton T.;Qin, Liya;Sheedy, Donna;Vetreno, Ryan P.;Zou, Jian
通讯作者：
Zou, Jian
尼古丁抑制小胶质细胞增殖并对全身缺血大鼠具有神经保护作用
影响因子：
5.1
作者：
Guan, Yan-Zhong;Jin, Xiu-Dong;Gao, Tian-Ming
通讯作者：
Gao, Tian-Ming
影响因子：
14.5
作者：
Jucaite, Aurelija;Svenningsson, Per;Farde, Lars
通讯作者：
Farde, Lars