The improvement of paliperidone on social communication deficits and its effect on GSK3&beta; phosphorylation in cerebral cortex

DONG Xiao-guang; HU Yan-lai; HU Tao; QU Bao-ming; CUI Gui-xiang; WANG Lan-dong; LI Tao

doi:10.13418/j.issn.1001-165x.2018.06.008

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

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

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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

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DONG Xiao-guang, HU Yan-lai, HU Tao, QU Bao-ming, CUI Gui-xiang, WANG Lan-dong, LI Tao. The improvement of paliperidone on social communication deficits and its effect on GSK3β phosphorylation in cerebral cortex[J]. Chinese Journal of Clinical Anatomy. 2018, 36(6): 637-641 https://doi.org/10.13418/j.issn.1001-165x.2018.06.008

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