Influence of xanthine administration on the mice hippocampus.

High rates of mental disorders, like depression and anxiety, often coexist with other illnesses. Chronic stress is a common risk factor for these disorders, yet we don't fully understand the mechanisms behind their development. Metabolomics has revealed a close link between purine and pyrimidine metabolism and depression/anxiety, showing increased serum xanthine levels in both humans and mice. While xanthine, part of purine metabolism, has various biological activities, its impact on brain function remains unclear. The hippocampus, crucial for memory and learning, is implicated in depression and anxiety. This study explores the effects of xanthine administration on spatial memory and anxiety-like behavior in mice. Results show that xanthine induces deficits in hippocampus-dependent spatial memory and a tendency toward anxiety-like behavior. RNA-seq analysis indicates that xanthine upregulates hemoglobin (Hb) genes related to oxygen transport in the hippocampus, particularly in neuronal cells. In vitro experiments reveal upregulation of both mouse-derived Hba-a1 and human-derived HBA2 by xanthine treatment. These findings suggest a connection between xanthine-induced Hb in the hippocampus and spatial memory deficits and anxiety. The study sheds light on the direct impact of xanthine on the brain and its potential role in depression and anxiety symptoms resulting from chronic stress.