Poly (I:C)-induced maternal immune activation generates impairment of reversal learning performance in offspring.

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Neurochemistry Pub Date : 2024-08-25 DOI:10.1111/jnc.16212
Eva Munarriz-Cuezva, Jose Javier Meana
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Abstract

Maternal immune activation (MIA) induces a variety of behavioral and brain abnormalities in offspring of rodent models, compatible with neurodevelopmental disorders, such as schizophrenia or autism. However, it remains controversial whether MIA impairs reversal learning, a basic expression of cognitive flexibility that seems to be altered in schizophrenia. In the present study, MIA was induced by administration of a single dose of polyriboinosinic-polyribocytidylic acid (Poly (I:C) (5 mg/kg i.p.)) or saline to mouse pregnant dams in gestational day (GD) 9.5. Immune activation was monitored through changes in weight and temperature. The offspring were evaluated when they reached adulthood (8 weeks) using a touchscreen-based system to investigate the effects of Poly (I:C) on discrimination and reversal learning performance. After an initial pre-training, mice were trained to discriminate between two different stimuli, of which only one was rewarded (acquisition phase). When the correct response reached above 80% values for two consecutive days, the images were reversed (reversal phase) to assess the adaptation capacity to a changing environment. Maternal Poly (I:C) treatment did not interfere with the learning process but induced deficits in reversal learning compared to control saline animals. Thus, the accuracy in the reversal phase was lower, and Poly (I:C) animals required more sessions to complete it, suggesting impairments in cognitive flexibility. This study advances the knowledge of how MIA affects behavior, especially cognitive domains that are impaired in schizophrenia. The findings support the validity of the Poly (I:C)-based MIA model as a tool to develop pharmacological treatments targeting cognitive deficits associated with neurodevelopmental disorders.

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多聚(I:C)诱导的母体免疫激活会损害后代的逆转学习能力。
母体免疫激活(MIA)会诱发啮齿类动物模型后代的各种行为和大脑异常,这与神经发育障碍(如精神分裂症或自闭症)是一致的。然而,MIA 是否会损害反向学习能力仍存在争议,反向学习能力是认知灵活性的基本表现形式,在精神分裂症中似乎会发生改变。在本研究中,通过给妊娠日(GD)为9.5的小鼠妊娠母体注射单剂量的多核苷酸-多核苷酸(Poly (I:C)(5 mg/kg i.p.))或生理盐水来诱导MIA。通过体重和体温的变化来监测免疫激活。后代成年后(8 周),使用触摸屏系统对其进行评估,以研究 Poly (I:C) 对辨别和逆转学习能力的影响。经过初步的预训练后,小鼠被训练辨别两种不同的刺激,其中只有一种刺激是有奖励的(习得阶段)。当小鼠连续两天的正确率达到 80% 以上时,就会将图像反转(反转阶段),以评估小鼠对不断变化的环境的适应能力。与盐水对照组相比,母体多聚物(I:C)处理不会干扰学习过程,但会导致逆转学习的缺陷。因此,逆转阶段的准确率较低,而且Poly (I:C)动物需要更多的训练才能完成,这表明它们的认知灵活性受到了影响。这项研究加深了人们对 MIA 如何影响行为的认识,尤其是精神分裂症患者认知领域的障碍。研究结果支持将基于Poly (I:C)的MIA模型作为开发针对神经发育障碍相关认知缺陷的药物治疗工具的有效性。
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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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