title: Effect of Cigarette Smoking on a Marker for Neuroinflammation: A [11C]DAA1106 Positron Emission Tomography Study.
abstract: In the brain, microglia continuously scan the surrounding extracellular space in order to respond to damage or infection by becoming activated and participating in neuroinflammation. When activated, microglia increase the expression of translocator protein (TSPO) 18 kDa, thereby making the TSPO expression a marker for neuroinflammation. We used the radiotracer [11C]DAA1106 (a ligand for TSPO) and positron emission tomography (PET) to determine the effect of smoking on availability of this marker for neuroinflammation. Forty-five participants (30 smokers and 15 non-smokers) completed the study and had usable data. Participants underwent a dynamic PET scanning session with bolus injection of [11C]DAA1106 (with smokers in the satiated state) and blood draws during PET scanning to determine TSPO affinity genotype and plasma nicotine levels. Whole-brain standardized uptake values (SUVs) were determined, and analysis of variance was performed, with group (smoker vs non-smoker) and genotype as factors, thereby controlling for genotype. Smokers and non-smokers differed in whole-brain SUVs (P=0.006) owing to smokers having 16.8% lower values than non-smokers. The groups did not differ in injected radiotracer dose or body weight, which were used to calculate SUV. An inverse association was found between whole-brain SUV and reported cigarettes per day (P<0.05), but no significant relationship was found for plasma nicotine. Thus, smokers have less [11C]DAA1106 binding globally than non-smokers, indicating less microglial activation. Study findings are consistent with much prior research demonstrating that smokers have impaired inflammatory functioning compared with non-smokers and that constituents of tobacco smoke other than nicotine affect inflammatory processes.
authors.affiliation: Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.|Department of Psychiatry, VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Brody
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Hubert
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Enoki
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Lizette Y
authors.initials: LY
authors.lastname: Garcia
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mamoun
authors.affiliation: Department of Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.|Department of Psychiatry, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Okita
authors.affiliation: Department of Psychiatry, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
authors.affiliation: Department of Psychiatry, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Nurmi
authors.affiliation: Department of Psychiatry, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Seaman
authors.affiliation: Department of Radiology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
mesh_terms: D000081:Acetamides / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D000073865:Cigarette Smoking / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D009538:Nicotine / Q000097:blood; D010647:Phenyl Ethers / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000081:Acetamides; D015415:Biomarkers; C118942:DAA 1106; D010647:Phenyl Ethers; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; D009538:Nicotine