A new 2-hit model combining serine racemase deletion and maternal separation displays behavioral and cognitive deficits associated with schizophrenia

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2024-10-21 DOI:10.1016/j.bbr.2024.115301

Caroline Lahogue, Michel Boulouard, François Menager, Thomas Freret, Jean-Marie Billard, Valentine Bouet

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引用次数: 0

Abstract

Schizophrenia (SCZ) is a multifactorial psychotic disorder characterized by positive and negative symptoms as well as cognitive impairments. To advance the current treatments, it is important to improve animal models by considering the multifactorial etiology, thus by combining different risk factors. The objective of our study was to explore in a new mouse model, the impact of genetic deletion of serine racemase (genetic vulnerability) combined with an early stress factor induced by maternal separation (early environmental exposure) in the context of SCZ development. The face validity of the model was assessed through a wide range of behavioral experiments. The 2-hit mice displayed an increased locomotor activity mimicking positive symptoms, working memory impairment, cognitive deficits and recognition memory alterations, which could reflect neophobia. This new multifactorial model therefore presents an interesting phenotype for modelling animal model with partial behavioral and cognitive deficits associated with SCZ.

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一种结合了丝氨酸消旋酶缺失和母体分离的新型双击模型显示出与精神分裂症相关的行为和认知障碍。

精神分裂症（SCZ）是一种多因素精神病，以阳性和阴性症状以及认知障碍为特征。为了推进当前的治疗方法，必须通过考虑多因素病因，从而结合不同的风险因素来改进动物模型。我们研究的目的是在一个新的小鼠模型中探讨丝氨酸消旋酶基因缺失（遗传易感性）与母体分离诱导的早期应激因素（早期环境暴露）对SCZ发展的影响。该模型的表面有效性通过一系列行为实验进行了评估。受到2次打击的小鼠表现出模仿阳性症状的运动活动增加、工作记忆受损、认知障碍和识别记忆改变，这可能反映了恐新症。因此，这种新的多因素模型为模拟与 SCZ 相关的部分行为和认知障碍的动物模型提供了一种有趣的表型。

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.