Transmission of behavioral and cognitive impairments across generations in rats subjected to prenatal valproic acid exposure

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY Birth Defects Research Pub Date : 2024-02-11 DOI:10.1002/bdr2.2309

Farahnaz Taheri, Sara Joushi, Khadijeh Esmaeilpour, Mohammad Navid Ebrahimi, Zahra Taherizadeh, Parichehr Taheri, Vahid Sheibani

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Abstract

Background

Autism spectrum disorder (ASD) represents an inheritable neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Numerous studies have underscored the significant roles played by genetic and environmental factors in the etiology of ASD, and these factors are known to perpetuate behavioral impairments across generations.

Objectives

The primary objective of this study was to assess the behavioral and cognitive attributes in the second filial (F2) generation of male and female rats, with a particular focus on those whose parents had been exposed to valproic acid (VPA) during embryonic development.

Methods

In this study, a cohort of 32 male and 32 female rats from the second filial (F2) generation, referred to as Mother.ASD, Father.ASD, or Both.ASD, was examined. These designations indicate whether the mother, father, or both parents had experienced embryonic exposure to valproic acid (600 mg/kg, i.p.). During adolescence, the F2 pups underwent behavioral and cognitive assessments, including open field testing, marble burying, social interaction evaluations, and Morris water maze tasks.

Results

Our data revealed that while both the Mother.ASD and Father.ASD groups, regardless of sex, exhibited elevated anxiety-like behavior in the open field test. Only the Mother.ASD group displayed repetitive behaviors and deficits in social memory. Additionally, spatial memory impairments were observed in both sexes. These findings highlight the transmission of autistic-like behaviors in the offspring of Mother.ASD rats from both sexes. Nevertheless, future research endeavors should be more targeted in identifying the specific genes responsible for this transmission.

Conclusion

In summary, our findings underscore the transmission of autistic-like behaviors, including anxiety-like behavior, repetitive actions, impairments in social interactions, and deficits in memory, to the offspring of the Mother.ASD group, irrespective of their sex.

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产前接触丙戊酸的大鼠行为和认知障碍的跨代传递

背景自闭症谱系障碍（ASD）是一种可遗传的神经发育疾病，其特点是社交沟通障碍和重复行为。大量研究强调了遗传和环境因素在自闭症谱系障碍病因中的重要作用，而且众所周知，这些因素会使行为障碍代代相传。目的本研究的主要目的是评估雌雄大鼠第二代孝子（F2）的行为和认知属性，尤其关注那些父母在胚胎发育期间接触过丙戊酸（VPA）的大鼠。方法在这项研究中，我们对第二代孝子（F2）中的 32 只雄性大鼠和 32 只雌性大鼠进行了研究，这些大鼠被称为母亲 ASD、父亲 ASD 或双亲 ASD。这些名称表示母亲、父亲或父母双方在胚胎期是否接触过丙戊酸（600 毫克/千克，静脉注射）。在青春期，F2 幼崽接受了行为和认知评估，包括开阔地测试、埋弹珠、社会互动评估和莫里斯水迷宫任务。结果我们的数据显示，母亲ASD组和父亲ASD组，无论性别如何，都在野外测试中表现出焦虑行为。只有母亲ASD组表现出重复行为和社会记忆缺陷。此外，男女儿童都出现了空间记忆障碍。这些发现突显了母亲型自闭症大鼠的后代中自闭症样行为的传播。然而，未来的研究工作应更有针对性地确定造成这种遗传的特定基因。结论总之，我们的研究结果表明，自闭症样行为，包括焦虑样行为、重复性动作、社会交往障碍和记忆缺陷，会遗传给 Mother.ASD 组的后代，不论其性别如何。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.