Abstract
Chronic long-term exposure to cuprizone causes severe brain demyelination in mice, which leads to changes in locomotion, working memory and anxiety. These findings suggest the importance of intact myelin for these behaviors. This study aimed to investigate the possible behavioral changes in mice with mild oligodendrocyte/myelin damage that parallels the white matter changes seen in the brains of patients with psychiatric disporders. We used the cuprizone-treated mouse model to test both tissue changes and behavioral functions (locomotor activity, anxiety status, and spatial working memory). The results showed that mice given cuprizone in their diet for 7 days had no significant myelin breakdown as evaluated by immunohistochemical staining for myelin basic protein, while the number of mature oligodendrocytes was reduced. The number and length of Caspr protein clusters, a structural marker of the node of Ranvier, did not change. The locomotor activity of the cuprizone-treated mice increased whereas their anxiety levels were lower than in normal controls; spatial working memory, however, did not change. These results, for the first time, link emotion-related behavior with mild white matter damage in cuprizone-treated mice.