Effect of overnight smoking abstinence on a marker for microglial activation: a [11C]DAA1106 positron emission tomography study
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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 [11C]DAA1106 (a radioligand for TSPO) in the brain than nonsmokers.
We sought to determine the effect of overnight smoking abstinence on [11C]DAA1106 binding in the brain.
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 [11C]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.
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.
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.
KeywordsTobacco dependence Cigarette withdrawal Positron emission tomography Magnetic resonance imaging [11C]DAA1106 Microglial activation Neuroinflammation
The authors thank Josephine Ribe and Christopher Davis for performing positron emission tomography scanning for the study.
This study was supported by the Tobacco-Related Disease Research Program (A.L.B. grant #588000), the National Institute on Drug Abuse (A.L.B. (R01 DA044909)), and the Department of Veterans Affairs, Office of Research and Development (CSR&D Merit Review Award I01 CX000412 (A.L.B.)). This research was also supported, in part, by the DOMONKAI fund from the Department of Psychiatry, Graduate School of Medicine, at Chiba University (K.O.), endowments from the Thomas P. and Katherine K. Pike Chair in Addiction Studies (E.D.L.) and Marjorie M. Green Trust (E.D.L.), and the National Institutes of Health (T32 DA024635 (L.S.)). The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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