Imaging [¹⁸F]FDG PET/CT Study of Nicotinic Acetylcholinergic Receptor α2 Knock-Out Mice and α2 Hypersensitive Mice...

Nicotinic 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 [¹⁸F]FDG PET/CT in α2 knockout (α2KO) and α2 hypersensitive (α2HS) mice.

Control (CN; 4M, 4F), α2 knockout (α2KO; 4M, 4F) and α2 hypersensitive (α2HS; 4M,4F), 12-16 month old mice were used. Mice were fasted and injected with [¹⁸F]FDG (3-5 MBq) while awake. After 40 minutes they underwent whole body PET/CT. On a separate day, nicotine challenge [¹⁸F]FDG studies were done. Reconstructed images were analyzed to obtain standard uptake values (SUV) of [¹⁸F]FDG in brain and interscapular brown adipose tissue (IBAT). Statistical analysis was performed.

The α2HS male mice exhibited the largest brain increase in [¹⁸F]FDG compared to α2KO male mice. The rank order of brain [¹⁸F]FDG uptake in the 3 groups: α2HS♂> CN♂> α2KO♂> CN♀= α2KO♀≥ α2HS♀. Nicotine treatment reduced brain [¹⁸F]FDG uptake in all mice. Females had lower [¹⁸F]FDG uptake compared to males and were less sensitive to α2 nAChR. In the case of IBAT, α2KO mice had significantly higher baseline [¹⁸F]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.

α2 nAChRs plays a significant role in brain activation as exhibited by the increase in [¹⁸F]FDG in α2HS mice. In the absence of regulatory control by the α2 nAChR, the α2KO mice IBAT exhibited higher [¹⁸F]FDG IBAT compared to controls and α2HS mice. Female mice were less affected by nicotine compared to the male mice. Overall, α2 nAChRs played a significant role in glucose metabolism in the brain and IBAT.