Related Experiment Video
Updated: Feb 21, 2026
HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice
Published on: July 9, 2016
Olig2 Silence Ameliorates Cuprizone-Induced Schizophrenia-Like Symptoms in Mice
Hongxia Liu1, Jinguo Zhai2, Bin Wang1
1Jining Neuro-Psychiatric Hospital, Jining, Shandong, China (mainland).
Abstract:
BACKGROUND The pathogenesis of schizophrenia is complex and oligodendrocyte abnormality is an important component of the pathogenesis found in schizophrenia. This study was designed to evaluate the function of olig2 in cuprizone-induced schizophrenia-like symptoms in a mouse model, and to assess the related mechanisms. MATERIAL AND METHODS The schizophrenia-like symptoms were modeled by administration of cuprizone in mice. Open-field and elevated-plus maze tests were applied to detect behavioral changes. Adenovirus encoding olig2 siRNA was designed to silence olig2 expression. Real-time PCR and western blotting were applied to detect myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), glial fibrillary acidic protein (GFAP) and olig2 expressions. RESULTS Open field test showed that the distance and time spent in the center area were significantly decreased in cuprizone mice (model mice) when compared with control mice (p<0.05). By contrast, olig2 silence could significantly increase the time and distance spent in the center area compared with the model mice (p<0.05). As revealed by elevated-plus maze test, the mice in the model group preferred the open arm and spent more time and distance in the open arm compared with control mice (p<0.05), while olig2 silence significantly reversed the abnormalities (p<0.05). Mechanically, MBP and CNPase expression were reduced in the model group compared with the control (p<0.05). However, olig2 silence reversed the reduction caused by cuprizone modeling (p<0.05). In addition, GFAP was elevated after cuprizone modeling compared with control (p<0.05), and was significantly inhibited by olig2 silence compared with model (p<0.05). CONCLUSIONS Cuprizone-induced schizophrenia-like symptoms involved olig2 upregulation. The silence of olig2 could prevent changes, likely through regulating MBP, CNPase, and GFAP expressions.
Insights
Oligodendrocyte abnormality is linked to schizophrenia. Silencing olig2 in a mouse model reversed schizophrenia-like behaviors and normalized myelin-related gene expression, suggesting olig2
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Schizophrenia pathogenesis involves complex mechanisms, with oligodendrocyte dysfunction being a key component.
- Oligodendrocytes are crucial for myelin sheath formation and maintenance in the central nervous system.
- Aberrant oligodendrocyte function is implicated in the neurobiological underpinnings of schizophrenia.
Purpose of the Study:
- To investigate the role of olig2 in cuprizone-induced schizophrenia-like symptoms in a mouse model.
- To elucidate the molecular mechanisms underlying olig2's function in this context.
- To assess the therapeutic potential of modulating olig2 expression.
Main Methods:
- Schizophrenia-like symptoms were induced in mice using cuprizone administration.
- Behavioral analysis was performed using open-field and elevated-plus maze tests.
- Olig2 expression was silenced using an adenovirus encoding olig2 siRNA, and gene/protein expression (MBP, CNPase, GFAP, olig2) was quantified via real-time PCR and western blotting.
Main Results:
- Cuprizone-induced mice exhibited decreased exploration of central areas and increased preference for open arms, indicative of anxiety and altered behavior.
- Olig2 silencing significantly reversed these behavioral abnormalities, restoring normal exploratory patterns.
- Olig2 silencing normalized the expression of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), which were reduced by cuprizone, and inhibited the elevated glial fibrillary acidic protein (GFAP) levels.
Conclusions:
- Cuprizone-induced schizophrenia-like symptoms are associated with upregulation of olig2.
- Silencing olig2 expression ameliorates behavioral deficits and molecular alterations in the mouse model.
- Olig2 plays a critical role in cuprizone-induced schizophrenia-like phenotypes, potentially through the regulation of myelin-related proteins and glial activation markers.
