帕潘立酮对社会交往缺陷的改善作用及对脑皮层GSK3β磷酸化的影响

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

摘要/Abstract

摘要：

目的　探讨新型非典型抗精神病药物帕潘立酮（Paliperidone）对精神分裂症（Schizophrenia）社会交往缺陷的改善作用及对脑皮层GSK3β磷酸化的影响。方法　应用地佐环平（dizocilpine，MK-801）连续腹腔注射，建立了精神分裂症模型小鼠。实验分为3组：对照组（腹腔注射同体积0.9%生理盐水）、MK-801组（模型组，给予0.5 mg·kg-1·d-1 MK-801腹腔注射，连续注射7 d）、MK-801+Paliperidone组（帕潘立酮治疗组，给予0.25 mg·kg-1·d-1 帕潘立酮+0.5 mg·kg-1·d-1 MK-801腹腔注射，连续注射7 d）。应用刻板性旋转实验评价精神分裂症模型的建立，并应用Miceprofile软件分析各组小鼠在自由活动状态下的社会交往行为变化。Western blotting(WB)检测鼠额叶皮层脑组织糖原合成激酶3β（glycogen synthase kinase 3β, GSK3β）的表达变化。结果　MK-801处理后明显增加实验小鼠的刻板性旋转动作，成功建立了精神分裂症小鼠模型。Miceprofile视频分析结果显示，模型鼠的交往接触次数和时长明显低于对照组（P<0.01）,帕潘立酮处理后，明显改善交往接触次数和时长（P<0.01）。WB分析结果显示MK-801明显降低脑皮层GSK3β的磷酸化水平，而帕潘立酮处理后可升高GSK3β磷酸化水平。结论　本项研究表明新型抗精神病药物帕潘立酮可改善动物社会交往缺陷行为，可能与增加脑皮层的磷酸化GSK3β有关。

关键词: , 帕潘立酮, 　社会交往, 　地佐环平(MK-801), 　糖原合成激酶3&beta, 　精神分裂症

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

董晓光,扈燕来,胡涛,瞿宝明,崔贵祥,王兰东,李涛. 帕潘立酮对社会交往缺陷的改善作用及对脑皮层GSK3β磷酸化的影响[J]. 中国临床解剖学杂志, 2018, 36(6): 637-641.

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.

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