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.
ACS Chem Neurosci
; 15(13): 2520-2531, 2024 Jul 03.
Article
in En
| MEDLINE
| ID: mdl-38875216
ABSTRACT
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 [18F]fluoro-deoxy-glucose ([18F]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 [18F]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 [18F]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, [18F]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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
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Smoking Cessation
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Positron-Emission Tomography
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Glucose
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
ACS Chem Neurosci
Year:
2024
Document type:
Article
Affiliation country:
France
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA