Behavioral alterations and demyelization of the corpus callosum in the mouse model of MK-801 induced schizophrenia
10.3936/j.issn.1002-0152.2013.11.001
- VernacularTitle:MK-801诱导的精神分裂症小鼠行为学和胼胝体髓鞘的改变
- Author:
Yun XIU
;
Lei ZHANG
;
Xuan QIU
;
Lin CHEN
;
Wei LU
;
Chao PENG
;
Guohua CHENG
;
Fenglei CHAO
;
Yong TANG
- Publication Type:Journal Article
- Keywords:
Schizophrenia;
MK-801;
NMDA antagonism;
Corpus callosum;
Demyelization
- From:
Chinese Journal of Nervous and Mental Diseases
2013;(11):641-645
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of white matter injuries in the schizophrenia induced by the NMDA re-ceptor antagonist. Methods Adult male C57BL/6J mice (8 week old) were equally divided into four groups. One group was sub-chronically treated with saline solution, and the other three groups were intraperitoneally treated with MK-801 at dose of 0.025 mg/mL (M1), 0.050 mg/mL (M2) and 0.100 mg/mL (M3) in a volume 10 ml per kilogram body weight. All ani-mals were tested using Morris water maze at the 9th-15th day and using the Hole Board exploration as well as Rota Rod performance tests on the 16th day. The myelin basic protein (MBP) and the ultrastructure of the myelin sheaths in the cor-pus callosum were then examined using immunohistochemical methods, transmission electron microscope technique and stereological methods. Results The repeated sub-chronic MK-801 treatment did not induce impairment of spatial learning and memory in Morris water maze. The MK-801 treatment at 0.25 mg/kg and 1.00 mg/kg but not at 0.50 mg/kg resulted in less exploration to a new environment. The myelin staining with anti-MBP antibody was less intense in all three schizo-phrenic groups when compared to saline control group (P<0.01). Furthermore, MK-801 treatment caused pathological al-terations of the myelin sheaths including segmental demyelination of myelinated fibers and splitting of myelin sheath lamel- lae in schizophrenic groups. The ratio of the injured myelinated nerve fibers in the corpus callosum of MK-801 treated mice [M3 group, (22.42 ± 4.24)%] was significantly higher when compared to the control mice [(3.84 ± 1.35)%,P<0.01)]. Conclusions The present study demonstrated the white matter damages, mainly low MBP expression and segmental demye-lization in the corpus callosum in the mice sub-chronic treated with MK-801, indicating that the white matter changes might be involved in the schizophrenia induced by NMDA antagonist.
