Related Experiment Video
Updated: Apr 30, 2026
Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice
Published on: September 28, 2022
White matter injuries induced by MK-801 in a mouse model of schizophrenia based on NMDA antagonism
Yun Xiu1, Xiang-Ru Kong, Lei Zhang
1Institute 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.
Abstract:
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.
Insights
Schizophrenia (SZ) is linked to white matter deficits. MK-801 induced a mouse model of SZ, revealing decreased white matter volume and myelin proteins, supporting the white matter hypothesis of schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Neurobiology
Background:
- The etiology of schizophrenia (SZ) remains complex and largely unknown.
- Neuroimaging and postmortem studies suggest white matter disturbances in SZ.
- The white matter deficits hypothesis of SZ requires further investigation.
Purpose of the Study:
- To test the white matter deficits hypothesis of SZ.
- To investigate the utility of an NMDA receptor antagonist MK-801 induced mouse model for studying SZ-related white matter abnormalities.
Main Methods:
- Induction of a mouse model of SZ using repeated chronic administration of NMDA receptor antagonist MK-801.
- Behavioral testing including open field test, hole-board test, and elevated plus maze.
- Assessment of white matter volume (total and corpus callosum) and myelin protein levels (myelin basic protein, 2', 3'-cyclic nucleotide 3'-phosphodiesterase).
- Histological examination for myelin sheath integrity.
Main Results:
- MK-801 treated mice exhibited behavioral changes consistent with SZ models: increased locomotor activity, reduced novel environment exploration, and heightened anxiety.
- No motor coordination or function impairments were observed in the MK-801 treated mice.
- Significant reductions in total white matter volume and corpus callosum volume were observed in MK-801 treated mice compared to controls.
- Decreased levels of myelin basic protein and 2', 3'-cyclic nucleotide 3'-phosphodiesterase were found in the MK-801 mouse model.
- Degenerative changes in myelin sheaths were observed in the MK-801 treated mice.
Conclusions:
- The study provides evidence supporting the white matter deficits hypothesis of schizophrenia.
- The MK-801 induced mouse model effectively replicates white matter abnormalities seen in schizophrenia.
- This animal model is valuable for exploring the mechanisms underlying white matter disturbances in SZ.
