Brain Glucose Metabolism as a Readout of the Central Nervous System Impact of Cigarette Smoke Exposure and Withdrawal and the Effects of NFL-101, as an Immune-Based Drug Candidate for Smoking Cessation Therapy

被引：0

作者：

Goutal, Sebastien ^{[1
]}

Tran, Thi ^{[2
,3
]}

Leroy, Claire ^{[1
]}

Benhamouda, Nadine ^{[2
,3
]}

Leterrier, Sarah ^{[1
]}

Saba, Wadad ^{[1
]}

Lafont, Bruno ^{[4
]}

Tartour, Eric ^{[2
,3
]}

Roelens, Marie ^{[2
,3
]}

Tournier, Nicolas ^{[1
]}

机构：

[1] Univ Paris Saclay, CEA, CNRS, Inserm,BioMaps, F-91401 Orsay, France

[2] Univ Paris Cite, INSERM, PARCC, F-75015 Paris, France

[3] Hop Necker Enfants Malad, Hop Europeen Georges Pompidou HEGP, AP HP, Dept Immunol, F-75015 Paris, France

[4] NFL Biosci, F-34170 Castelnau Le Lez, France

来源：

ACS CHEMICAL NEUROSCIENCE | 2024年 / 15卷 / 13期

关键词：

cigarette smoke; neuroimaging; neuro-immunopharmacology; nicotine; positron emission tomography; substanceuse disorder; tobacco; smoking cessation therapy; IN-VIVO; MOUSE-BRAIN; TOBACCO USE; NICOTINE; CLEARANCE; VACCINE; SIGNAL; VIRUS; CUES; PET;

D O I：

10.1021/acschemneuro.4c00204

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neuroimaging biomarkers are needed to investigate the impact of smoking withdrawal on brain function. NFL-101 is a denicotinized aqueous extract of tobacco leaves currently investigated as an immune-based smoking cessation therapy in humans. However, the immune response to NFL-101 and its ability to induce significant changes in brain function remain to be demonstrated. Brain glucose metabolism was investigated using [F-18]fluoro-deoxy-glucose ([F-18]FDG) PET imaging in a mouse model of cigarette smoke exposure (CSE, 4-week whole-body inhalation, twice daily). Compared with control animals, the relative uptake of [F-18]FDG in CSE mice was decreased in the thalamus and brain stem (p < 0.001, n = 14 per group) and increased in the hippocampus, cortex, cerebellum, and olfactory bulb (p < 0.001). NFL-101 induced a humoral immune response (specific IgGs) in mice and activated human natural-killer lymphocytes in vitro. In CSE mice, but not in control mice, single-dose NFL-101 significantly increased [F-18]FDG uptake in the thalamus (p < 0.01), thus restoring normal brain glucose metabolism after 2-day withdrawal in this nicotinic receptor-rich region. In tobacco research, [F-18]FDG PET imaging provides a quantitative method to evaluate changes in the brain function associated with the withdrawal phase. This method also showed the CNS effects of NFL-101, with translational perspectives for future clinical evaluation in smokers.

引用

页码：2520 / 2531

页数：12