The myelinated fiber loss in the corpus callosum of mouse model of schizophrenia induced by MK-801.
Previous magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) investigations have shown that the white matter volume and fractional anisotropy (FA) were decreased in schizophrenia (SZ), which indicated impaired white matter integrity in SZ. However, the mechanism underlying these abnormalities has been less studied. The current study was designed to investigate the possible reasons for white matter abnormalities in the mouse model of SZ induced by NMDA receptor antagonist using the unbiased stereological methods and transmission electron microscope technique. We found that the mice treated with MK-801 demonstrated a series of schizophrenia-like behaviors including hyperlocomotor activity and more anxiety. The myelinated fibers in the corpus callosum (CC) of the mice treated with MK-801 were impaired with splitting lamellae of myelin sheaths and segmental demyelination. The CC volume and the total length of the myelinated fibers in the CC of the mice treated with MK-801 were significantly decreased by 9.4% and 16.8% when compared to those of the mice treated with saline. We further found that the loss of the myelinated fibers length was mainly due to the marked loss of the myelinated nerve fibers with the diameter of 0.4-0.5 μm. These results indicated that the splitting myelin sheaths, demyelination and the loss of myelinated fibers with small diameter might provide one of the structural bases for impaired white matter integrity of CC in the mouse model of SZ. These results might also provide a baseline for further studies searching for the treatment of SZ through targeting white matter.
Institute of Life Science, Chongqing Medical University, Chongqing 400016, PR China; Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, PR China.
Yun
Y
Xiu
Department of Pediatric Surgical Oncology, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
Xiang-ru
XR
Kong
Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, PR China.
Lei
L
Zhang
Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, PR China.
Xuan
X
Qiu
Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, PR China; Department of Geriatrics, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, PR China.
Yuan
Y
Gao
Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, PR China; Department of Physiology, Chongqing Medical University, Chongqing 400016, PR China.
Chun-xia
CX
Huang
Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, PR China.
Feng-lei
FL
Chao
Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, PR China.
San-rong
SR
Wang
Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: ytang062@163.com.
Yong
Y
Tang
D000465:Algorithms; D000818:Animals; D054022:Cerebrum / Q000473:pathology; D003337:Corpus Callosum / Q000473:pathology*; D003711:Demyelinating Diseases / Q000209:etiology / Q000473:pathology; D003936:Diagnosis, Computer-Assisted; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009413:Nerve Fibers, Myelinated / Q000473:pathology* / Q000648:ultrastructure; D012559:Schizophrenia / Q000139:chemically induced* / Q000150:complications / Q000473:pathology*
D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate
Corpus callosum; Myelinated fiber; Schizophrenia; Stereology