Chinese Journal Of Clinical Anatomy ›› 2018, Vol. 36 ›› Issue (6): 637-641.doi: 10.13418/j.issn.1001-165x.2018.06.008

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The improvement of paliperidone on social communication deficits and its effect on GSK3β phosphorylation in cerebral cortex

DONG Xiao-guang1, HU Yan-lai2, HU Tao1, QU Bao-ming2, CUI Gui-xiang3, WANG Lan-dong3, LI Tao4   

  1. 1.Department of Spine Surgery, Qingdao Orthopedic Hospital, Qingdao 266101, China; 2.Department of Anatomy of School of Basic Medical Sciences, Shandong University,Jinan 250012, China; 3. Rehabilitation Hospital of Jinan, Jinan 250100, China; 4. Department of Neurosurgery, the No.4 Hospital of Jinan, Jinan 250031, China
  • Received:2018-10-10 Online:2018-11-25 Published:2018-12-29

Abstract:

Objective To investigate the effect of a new atypical antipsychotic drug paliperidone on social communication defects in schizophrenia and the possible mechanism of its effect on the GSK3β phosphorylation in the cerebral cortex. Methods Dizocilpine (MK-801) was given to mice by intraperitoneal injection continuously to establish the model of schizophrenia. The mice were divided into 3 groups: control group (mice were given by intraperitoneal injection with the same volume of 0.9% saline as other groups), MK-801 group (model group, 0.5 mg·kg-1·d-1 MK-801 was given to mice by intraperitoneal injection, for 7d ), and MK-801+Paliperidone group (paliperidone treatment group, 0.25 mg·kg-1·d-1 paliperidone and 0.5 mg·kg-1·d-1 MK-801 were given to mice by intraperitoneal injection, for 7d). The establishment of the schizophrenia model was evaluated with the stereotyped rotation experiment. Miceprofile software was used to analyze the changes of social communication behavior in the free activity of mice. Western blotting was used to detect the expression of the glycogen kinase 3 beta in the frontal cortex of the mice. Results MK-801 treatment significantly increased the stereotyped rotation of the experimental mice and successfully established schizophrenia mouse model. Miceprofile video analysis showed that the number of contact times and duration of the model mice was significantly lower than that of the control group (P<0.01). After treatment with paliperidone, the number and duration of contacts were obviously improved (P<0.01). The results of WB analysis showed that MK-801 significantly decreased the phosphorylation level of GSK3β in the cerebral cortex, and the phosphorylation level of GSK3β could be increased after paliperidone treatment. Conclusions This study shows that paliperidone as a new antipsychotic drug can improve the social communication deficits in animals, which may be related to increased phosphorylation of GSK3β in the cerebral cortex.

Key words: Paliperidone,  Social communication,  Dizocilpine(MK-801),  Glycogen synthase kinase 3 beta(GSK3&beta, ),  Schizophrenia