Other studies have also demonstrated the brain-specific distribution of ALDH2 in mice, particularly in neurons within the prefrontal cortex (106). Deleting the Aldh2 gene, specifically in the forebrain neuronal lineage, reduced alcohol intake, leading to lower BAC in knockout mice compared to wild-type mice. However, despite the reduced BAC, acetaldehyde accumulated in the prefrontal cortex of these mice, impairing behavioral performance in tasks related to spatial learning, working memory, and prefrontal cortical functions deteriorated (106). These findings underscore the importance of understanding human brain alcohol metabolism, particularly how region-specific and cell-type specific enzyme activity and individual factors influence its effects, including alcohol toxicity. For example, data from the Human Protein Atlas indicate that astrocytes, but not neurons, express catalase, whereas neurons, but not astrocytes, express CYP2E1 in humans (151, 152).
