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吸烟暂停一夜对小胶质细胞激活标志物的影响:[C]DAA1106 正电子发射断层扫描研究。

Effect of overnight smoking abstinence on a marker for microglial activation: a [C]DAA1106 positron emission tomography study.

机构信息

Department of Psychiatry, University of California, San Diego/VA San Diego Healthcare System, San Diego, CA, USA.

Department of Research, VA San Diego Healthcare System, 3350 La Jolla Village Drive (116A), San Diego, CA, 92161, USA.

出版信息

Psychopharmacology (Berl). 2018 Dec;235(12):3525-3534. doi: 10.1007/s00213-018-5077-3. Epub 2018 Oct 20.

Abstract

RATIONALE

Microglia are the main immune cells in the central nervous system and participate in neuroinflammation. When activated, microglia express increased levels of the translocator protein 18 kDa (TSPO), thereby making TSPO availability a marker for neuroinflammation. Using positron emission tomography (PET) scanning, our group recently demonstrated that smokers in the satiated state had 16.8% less binding of the radiotracer [C]DAA1106 (a radioligand for TSPO) in the brain than nonsmokers.

OBJECTIVES

We sought to determine the effect of overnight smoking abstinence on [C]DAA1106 binding in the brain.

METHODS

Forty participants (22 smokers and 18 nonsmokers) completed the study (at one of two sites) and had usable data, which included images from a dynamic [C]DAA1106 PET scanning session (with smokers having been abstinent for 17.9 ± 2.3 h) and a blood sample for TSPO genotyping. Whole brain standardized uptake values (SUVs) were determined, and analysis of variance was performed, with group (overnight abstinent smoker vs. nonsmoker), site, and TSPO genotype as factors, thereby controlling for site and genotype.

RESULTS

Overnight abstinent smokers had lower whole brain SUVs (by 15.5 and 17.0% for the two study sites) than nonsmokers (ANCOVA, P = 0.004). The groups did not significantly differ in injected radiotracer dose or body weight, which were used to calculate SUV.

CONCLUSIONS

These results in overnight abstinent smokers are similar to those in satiated smokers, indicating that chronic cigarette smoking leads to global impairment of microglial activation which persists into early abstinence. Other explanations for study results, such as smoking leading to reduced numbers of microglia or smokers having more rapid metabolism of the radiotracer than nonsmokers, are also possible.

摘要

背景

小胶质细胞是中枢神经系统中的主要免疫细胞,参与神经炎症。当被激活时,小胶质细胞表达高水平的转位蛋白 18 kDa(TSPO),从而使 TSPO 的可用性成为神经炎症的标志物。使用正电子发射断层扫描(PET)扫描,我们的研究小组最近表明,在饱食状态下的吸烟者的大脑中,放射性示踪剂 [C]DAA1106(TSPO 的放射性配体)的结合减少了 16.8%,而非吸烟者则没有减少。

目的

我们试图确定一夜吸烟戒断对大脑中 [C]DAA1106 结合的影响。

方法

40 名参与者(22 名吸烟者和 18 名非吸烟者)完成了这项研究(在两个地点之一),并获得了可用的数据,其中包括动态 [C]DAA1106 PET 扫描(吸烟者已戒断 17.9±2.3 小时)和血液样本的 TSPO 基因分型。确定了全脑标准化摄取值(SUV),并进行方差分析,以组(一夜戒断的吸烟者与非吸烟者)、地点和 TSPO 基因型为因素,从而控制了地点和基因型的影响。

结果

一夜戒断的吸烟者的全脑 SUV 比非吸烟者低(两个研究地点分别低 15.5%和 17.0%)(ANCOVA,P=0.004)。两组在注射的放射性示踪剂剂量或体重方面没有显著差异,这些因素用于计算 SUV。

结论

这些在一夜戒断的吸烟者中的结果与在饱食的吸烟者中的结果相似,表明慢性吸烟导致小胶质细胞激活的全面受损,这种损伤在早期戒断时仍然存在。其他可能导致研究结果的解释,如吸烟导致小胶质细胞数量减少或吸烟者比非吸烟者更快地代谢放射性示踪剂,也是可能的。

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Neuroinflammation: Microglia and T Cells Get Ready to Tango.神经炎症:小胶质细胞和T细胞准备共舞。
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