White matter injuries induced by MK-801 in a mouse model of schizophrenia based on NMDA antagonism.
The etiology of schizophrenia (SZ) is complex and largely unknown. Neuroimaging and postmortem studies have suggested white matter disturbances in SZ. In the present study, we tested the white matter deficits hypothesis of SZ using a mouse model of SZ induced by NMDA receptor antagonist MK-801. We found that mice with repeated chronic MK-801 administration showed increased locomotor activity in the open field test, less exploration of a novel environment in the hole-board test, and increased anxiety in the elevated plus maze but no impairments were observed in coordination or motor function on accelerating rota-rod. The total white matter volume and corpus callosum volume in mice treated with MK-801 were significantly decreased compared to control mice treated with saline. Myelin basic protein and 2', 3'-cyclic nucleotide 3'-phosphodiesterase were also significantly decreased in the mouse model of SZ. Furthermore, we observed degenerative changes of myelin sheaths in the mouse model of SZ. These results provide further evidence of white matter deficits in SZ and indicate that the animal model of SZ induced by MK-801 is a useful model to investigate mechanisms underlying white matter abnormalities in SZ.
Institute of Life Science, Chongqing Medical University, Chongqing, People's Republic of China; Department of Histology and Embryology, Chongqing Medical University, Chongqing, People's Republic of China.
Yun
Y
Xiu
Xiang-Ru
XR
Kong
Lei
L
Zhang
Xuan
X
Qiu
Feng-Lei
FL
Chao
Chao
C
Peng
Yuan
Y
Gao
Chun-Xia
CX
Huang
San-Rong
SR
Wang
Yong
Y
Tang
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009043:Motor Activity; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D066127:White Matter / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D018691:Excitatory Amino Acid Antagonists; C436006:Mbp protein, rat; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases
NMDA antagonism; corpus callosum; demyelization; schizophrenia