Tianeptine Affects the Improvement of Behavioral Defects, such as Schizophrenia, Caused by Maternal Immune Activation in the Mice Offspring.

Jun-Tack Kwon, Kooseung Jung
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Abstract

Background: Simultaneously with studies on animal models of fetal-induced maternal immune activation, related studies documented behavior, neurophysiological, and/or neurochemical disorders observed in some neuropsychiatric disorders, including autism and schizophrenia.

Objective: To investigate whether treatment tianeptine might ameliorate maternal immune activation (MIA)-induced behavioral deficits in the offspring.

Materials and methods: The pregnant mice were injected through tail vein injection at a concentration of 5 mg/kg of polyriboinosinic-polyribocytidilic acid (polyI:C) and/or used saline as a vehicle. The injection was performed on the 9th day of pregnancy. Each group of MIA offspring was subjected to vehicle, clozapine, or tianeptine treatment.

Results: In prepulse inhibition (PPI) test, oral treatment with tianeptine ameliorated MIA-induced sensorimotor gating deficit. Most behavioral parameters of social interaction test (SIT), forced swimming test (FST), and open field test (OFT) were significantly changed in the MIA offspring. Tianeptine treatment significantly recovered behavioral changes observed in the SIT, OFT, and FST. In order to confirm expression level of neurodevelopmental proteins, immunohistochemical image analysis and Western blot were performed, and the medial prefrontal cortex (mPFC) was targeted. As a result, it was confirmed that the neurodevelopmental proteins were decreased, which was recovered after administration of tianeptine to MIA offspring.

Conclusion: Tianeptine might be useful for treating psychiatric disorders with neurodevelopmental issues.

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天奈肽影响小鼠后代由母体免疫激活引起的行为缺陷,如精神分裂症的改善。
背景:在对胎儿诱导的母体免疫激活动物模型进行研究的同时,相关研究记录了在一些神经精神疾病(包括自闭症和精神分裂症)中观察到的行为、神经生理和/或神经化学障碍。目的:探讨天奈肽治疗是否能改善母体免疫激活(MIA)引起的后代行为缺陷。材料与方法:将浓度为5 mg/kg的聚核糖素-聚核糖素二酸(polyI:C)经尾静脉注射给孕鼠,或以生理盐水为载药。注射于妊娠第9天进行。每组MIA后代均接受载体、氯氮平或天奈汀治疗。结果:在脉冲前抑制(PPI)试验中,口服天奈汀可改善mia诱导的感觉运动门控缺陷。社会互动测试(SIT)、强迫游泳测试(FST)和开放场地测试(OFT)的大部分行为参数在MIA子代中发生了显著变化。在SIT、OFT和FST中观察到,天奈肽治疗可显著恢复行为改变。以内侧前额叶皮层(medial prefrontal cortex, mPFC)为靶点,采用免疫组化图像分析和Western blot方法确定神经发育蛋白的表达水平。结果证实,MIA后代的神经发育蛋白减少,在给药后恢复。结论:天奈肽可用于治疗伴有神经发育问题的精神障碍。
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来源期刊
Central nervous system agents in medicinal chemistry
Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology
CiteScore
2.10
自引率
0.00%
发文量
21
期刊介绍: Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.
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