Locomotor activity and anxiety status, but not spatial working memory, are affected in mice after brief exposure to cuprizone
1Mental Health Center, Shantou University, Shantou 515065, China
2Department of Psychiatry, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, R3E 0W2, Canada
3Department of Cardiology, China-Japan Friendship Hospital of Jilin University, Changchun 130041, China
4Department of Ophthalmology, Second Hospital of Jilin University, Changchun 130041, China
5Department of Neuropsychiatry, ZhongDa Hospital Affiliated with Southeast University, Nanjing 210009, China
6Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
7Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, R3E 0J9, Canada
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 cuprizonetreated 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 cuprizonetreated 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.
Keywords
myelination; oligodendrocyte; locomotor activity; anxiety; spatial working memory; cuprizone; mouse
