Demyelination in the juvenile period, but not in adulthood, leads to long-lasting cognitive impairment and deficient social interaction in mice.
BACKGROUND
Dysmyelination is hypothesized to be one of the causes of schizophrenic symptoms. Supporting this hypothesis, demyelination induced by cuprizone was recently shown to cause schizophrenia-like symptoms in adult rodents [Xiao L, Xu H, Zhang Y, Wei Z, He J, Jiang W, et al. Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. Mol Psychiatry 2008;13:697-708]. The present study asked if the timing of demyelination (i.e., juvenile period or adulthood) influenced abnormal behavior.


METHODS
B57BL/6 mice were fed with 0.2% cuprizone either from postnatal day 29 (P29) to P56 (early demyelination group) or from P57 to P84 (late demyelination group), and then returned to normal mouse chow until P126, when the behavioral analysis was initiated.


RESULTS
In both groups, the intake of cuprizone for 28 days produced massive demyelination in the corpus callosum by the end of the treatment period, and subsequent normal feeding restored myelination by P126. In a Y-maze test, the spatial working memory was impaired in both groups right after the cuprizone feeding ceased, consistent with previous studies, whereas only the early demyelination group exhibited impaired working memory after remyelination took place. In an open field test, social interactions were decreased in the early demyelination group, but not in the late group. Novel cognition and anxiety-related behaviors were comparable between the two groups.


CONCLUSIONS
Our findings suggest that the timing of demyelination has substantial impacts on behaviors of adult mice.
Makinodan
Manabu
M
Department of Psychiatry, Nara Medical University Faculty of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan. mmm@naramed-u.ac.jp
Yamauchi
Takahira
T
Tatsumi
Kouko
K
Okuda
Hiroaki
H
Takeda
Tomohiko
T
Kiuchi
Kuniaki
K
Sadamatsu
Miyuki
M
Wanaka
Akio
A
Kishimoto
Toshifumi
T
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology* / Q000523:psychology; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology*; D005260:Female; D007398:Interpersonal Relations; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
D003471:Cuprizone