Imaging [18F]FDG PET/CT pilot study of nicotinic acetylcholinergic receptor α2 knock-out mice and α2 hypersensitive mice compared to control mice: Male-female differences and nicotine effects
Christopher Liang, Titus E. Tucker, Ashlee D. L. Coronel, Ellen H. N. Nguyen, Janet L. Nguyen, Irakli Intskirveli, Ronit Lazar, Raju Metherate, Jogeshwar MukherjeeNicotinic acetylcholinergic receptors (nAChRs), comprising of α and β subunits are present in the brain and whole body. The less abundant α2-subunit is a fast-acting receptor subtype and plays an important role in cognition and learning. To understand cellular functional consequences, this study evaluated glucose metabolism using [ 18 F]FDG PET/CT in α2 knockout (α2KO) and α2 hypersensitive (α2HS) mice.
Control (CN; 4M, 3F), α2 knockout (α2KO; 4M, 4F) and α2 hypersensitive (α2HS; 4M,4F), 12–16 month old mice were used. Mice were fasted and injected with [ 18 F]FDG (3–5 MBq) while awake. After 40 minutes they underwent whole body PET/CT. On a separate day, nicotine challenge [ 18 F]FDG studies were done. Reconstructed images were analyzed to obtain standard uptake values (SUV) of [ 18 F]FDG in brain and interscapular brown adipose tissue (IBAT). Statistical analysis was performed comparing the three groups of mice. The α2HS male mice exhibited the largest brain increase in [ 18 F]FDG compared to α2KO male mice. The rank order of brain [ 18 F]FDG uptake in the three groups: α2HS♂ > CN♂ > α2KO♂ > CN♀= = α2KO♀ ≥ α2HS♀. Nicotine treatment reduced brain [ 18 F]FDG uptake in all mice. Females had lower [ 18 F]FDG uptake compared to males and were less sensitive to α2 nAChR. In the case of IBAT, α2KO mice had significantly higher baseline [ 18 F]FDG uptake compared to the other two groups: α2KO♂ > α2KO♀ > α2HS♀ > α2HS♂ > CN♀ > CN♂. Nicotine decreased IBAT in α2KO mice rather than increase as observed in CN and α2HS mice.This preliminary study shows that α2 nAChRs play a significant role in brain activation as exhibited by the increase in [ 18 F]FDG in α2HS mice. In the absence of regulatory control by the α2 nAChR, the α2KO mice IBAT exhibited higher [ 18 F]FDG uptake compared to controls and α2HS mice. Female mice were less affected by nicotine compared to the male mice.