09 October 2017 : Animal Research
Olig2 Silence Ameliorates Cuprizone-Induced Schizophrenia-Like Symptoms in Mice
Hongxia Liu1A, Jinguo Zhai2BCDE*, Bin Wang1C, Maosheng Fang3BCDOI: 10.12659/MSM.903842
Med Sci Monit 2017; 23:4834-4840
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.
Keywords: Glial Fibrillary Acidic Protein, Schizophrenia
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