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.
Sébastien GoutalThi TranClaire LeroyNadine BenhamoudaSarah LeterrierWadad SabaBruno LafontÉric TartourMarie RoelensNicolas TournierPublished in: ACS chemical neuroscience (2024)
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 [ 18 F]fluoro-deoxy-glucose ([ 18 F]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 [ 18 F]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 [ 18 F]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, [ 18 F]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.
Keyphrases
- pet imaging
- smoking cessation
- resting state
- white matter
- functional connectivity
- positron emission tomography
- immune response
- cerebral ischemia
- mouse model
- pet ct
- replacement therapy
- endothelial cells
- randomized controlled trial
- high fat diet induced
- physical activity
- blood pressure
- high resolution
- brain injury
- bone marrow
- subarachnoid hemorrhage
- deep brain stimulation
- blood glucose
- cerebrospinal fluid
- electronic health record
- drug induced
- insulin resistance
- high speed
- study protocol
- ionic liquid