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母体免疫激活模型中自闭症谱系障碍群体行为变异的形态学关联

Morphological Correlates of Behavioral Variation in Autism Spectrum Disorder Groups in A Maternal Immune Activation Model.

作者信息

Ünal Dilek, Varol Aslıhan Bahadır, Köse Tansu Bilge, Koçak Emine Eren

机构信息

Hacettepe University School of Medicine, Department of Child and Adolescent Psychiatry, Ankara, Turkey.

Hacettepe University School of Medicine, Neurological and Psychiatric Sciences Institute, Ankara, Turkey.

出版信息

Noro Psikiyatr Ars. 2024 Jun 11;67(3):195-201. doi: 10.29399/npa.28637. eCollection 2024.

Abstract

INTRODUCTION

Clinical heterogeneity is one of the biggest challenges for researchers studying underlying neurobiological mechanisms in Autism Spectrum Disorder (ASD). We aimed to use polyinosinic-polycytidylic acid [Poly (I:C)] induced maternal immune activation mice model to investigate the behavioral variation and the role of brain circuits related to symptom clusters in ASD. For this purpose, behavioral tests were applied to offsprings and regional thickness was measured from histological brain sections in medial prefrontal cortex, hippocampus and striatum.

METHODS

Pups of intraperitoneal Poly (I:C)-applied mothers (n: 14) and phosphate buffered saline-applied mothers (n: 6) were used for this study. We used three chamber socialization test and social memory test to evaluate social behavior deficit in mice. Marble burying test was used for assessing stereotypic behavior and new object recognition test for learning and cognitive flexibility. Three subgroups (n: 4 for each) were determined according to behavioral test parameters. Regional thickness was measured in medial prefrontal cortex, hippocampus and striatum and compared between subgroups.

RESULTS

We detected that the behavioral differences were distributed in a spectrum as expected in the clinic and also detected increased hippocampus thickness in the stereotypic behavior dominant Poly (I:C) subgroup.

CONCLUSION

Poly (I:C) induced maternal immune activation model creates the behavioral variation and cortical development differences that are seen in relation with symptom groups in ASD.

摘要

引言

临床异质性是研究自闭症谱系障碍(ASD)潜在神经生物学机制的研究人员面临的最大挑战之一。我们旨在使用聚肌苷酸-聚胞苷酸[Poly(I:C)]诱导的母体免疫激活小鼠模型,来研究行为变化以及与ASD症状群相关的脑回路的作用。为此,对后代进行行为测试,并测量内侧前额叶皮质、海马体和纹状体组织学脑切片的区域厚度。

方法

本研究使用腹腔注射Poly(I:C)的母亲所生幼崽(n = 14)和注射磷酸盐缓冲盐水的母亲所生幼崽(n = 6)。我们使用三室社交测试和社交记忆测试来评估小鼠的社交行为缺陷。使用大理石掩埋测试评估刻板行为,使用新物体识别测试评估学习和认知灵活性。根据行为测试参数确定三个亚组(每组n = 4)。测量内侧前额叶皮质、海马体和纹状体的区域厚度,并在亚组之间进行比较。

结果

我们检测到行为差异如临床上预期的那样呈谱系分布,并且在以刻板行为为主的Poly(I:C)亚组中还检测到海马体厚度增加。

结论

Poly(I:C)诱导的母体免疫激活模型产生了与ASD症状群相关的行为变化和皮质发育差异。

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