Species differences in cholinesterase expression and their translational impact

Rodents, particularly rats and mice, are essential models in cholinergic research due to their physiological and genetic similarities to humans. However, species-specific differences in cholinesterase expression can complicate the interpretation and translation of findings to human biology. To address this, we compared the expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) across key tissues like liver, brain, hypothalamus, lungs, and spleen in rats and mice, using RT-qPCR. Expression levels were normalized to liver expression within each species. Human reference gene expression data were obtained from the Human Protein Atlas to enable cross-species comparison. The inter-species distribution of AChE mRNA expression was largely conserved across mice, rats, and humans, with consistently high levels observed in the brain and heart atria. In contrast, BChE mRNA expression displayed a species-specific pattern: the highest levels were found in the left ventricles of the mouse heart, throughout the heart and brain in rats, and predominantly in the liver in humans. These findings highlight the need to distinguish between AChE and BChE when studying cholinergic regulation, as species- and tissue-specific differences may significantly affect the translational relevance of rodent models in cholinergic research and drug development.