The expression profile of type 1 equilibrative nucleoside transporter in aged C57BL/6J mouse brain

The type 1 equilibrative nucleoside transporter (ENT1) is essential for regulating extracellular adenosine levels and has been implicated in various psychiatric disorders. While previous studies have investigated the expression of ENT1 in fetal and neonatal brains, its neuroanatomical distribution in adult and aged mouse brains has not been fully elucidated. Therefore, in this study, we utilize immunohistochemistry and double-immunofluorescence techniques to map the expression of ENT1 across various brain regions. Our findings demonstrate that ENT1-positive cells are widely distributed throughout the brain, with particularly high expression observed in the cerebral cortex and hippocampus. ENT1 is expressed predominantly in neurons, particularly in cholinergic, dopaminergic and glutamatergic neurons. Furthermore, ENT1 is localized primarily to the mitochondria and lysosomes and is expressed to a lesser extent in the Golgi apparatus and endoplasmic reticulum. Notably, we find an age-dependent increase in ENT1 expression in the cerebral cortex, suggesting a potential role in age-related cognitive functions. This study highlights the regionally specific expression of ENT1 in the brain, providing a new morphological basis for understanding its potential roles in brain physiology. Additionally, given its involvement in neurotransmitter regulation, ENT1 may have important implications for neurological and psychiatric disorders. This work lays the groundwork for future studies exploring the implications of ENT1 in neurodegenerative diseases and other aging-related brain disorders.