Sex-dependent alterations of inflammatory factors, oxidative stress, and histopathology of the brain-gut axis in a VPA-induced autistic-like model of rats

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2024-04-02 DOI:10.1002/bdr2.2310

Zahra Salari, Amirhossein Moslemizadeh, Sara Sheibani Tezerji, Nazanin Sabet, Ali Saeidpour Parizi, Mohammad Khaksari, Vahid Sheibani, Elham Jafari, Sara Shafieipour, Hamideh Bashiri

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Abstract

Introduction

In this study, we aimed to investigate the inflammatory factors, oxidative stress, and histopathological consequences of the brain-gut axis in male and female rats prenatally exposed to VPA.

Methods

Pregnant Wistar rats were randomly divided into two groups. The animals received saline, and valproic acid (VPA) (600 mg/kg, i.p.) on embryonic day 12.5 (E12.5). All offspring were weaned on postnatal day 21, and the experiments were done in male and female rats on day 60. The brain and intestine tissues were extracted to assess histopathology, inflammation, and oxidative stress.

Results

An increase of interleukin-1β (IL-1β) and interleukin-6 (IL-6) and a decrease of interleukin-10 (IL-10) were observed in the two sexes and two tissues of the autistic rats. In the VPA-exposed animals, malondialdehyde (MDA) and protein carbonyl (PC) increased in the brain of both sexes and the intestines of only the males. The total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased in both tissues of male and female autistic groups. Histopathological evaluation showed that the %apoptosis of the cortex in the autistic male and female groups was more than in controls whereas this parameter in the CA1 and CA3 was significant only in the male rats. In the intestine, histopathologic changes were seen only in the male autistic animals.

Conclusion

The inflammatory and antioxidant factors were in line in the brain-gut axis in male and female rats prenatally exposed to VPA. Histopathological consequences were more significant in the VPA-exposed male animals.

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VPA诱导的大鼠自闭症样模型中炎症因子、氧化应激和脑肠轴组织病理学的改变与性别有关。

引言本研究旨在探讨产前暴露于 VPA 的雌雄大鼠脑-肠轴的炎症因子、氧化应激和组织病理学后果：方法：将怀孕的 Wistar 大鼠随机分为两组。方法：将妊娠 Wistar 大鼠随机分为两组，一组接受生理盐水，另一组在胚胎 12.5 天（E12.5）接受丙戊酸（VPA）（600 毫克/千克，静脉注射）。所有后代均于出生后第 21 天断奶，实验于第 60 天在雄性和雌性大鼠中进行。提取脑组织和肠组织以评估组织病理学、炎症和氧化应激：结果：在自闭症大鼠的两种性别和两种组织中观察到白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）增加，白细胞介素-10（IL-10）减少。在暴露于 VPA 的动物中，雌雄大鼠大脑中的丙二醛（MDA）和蛋白质羰基（PC）都有所增加，只有雄性大鼠肠道中的丙二醛和蛋白质羰基有所增加。雌雄自闭症组动物两种组织的总抗氧化能力（TAC）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）均明显下降。组织病理学评估显示，雌雄自闭症组大鼠大脑皮层的凋亡率高于对照组，而只有雄性大鼠的 CA1 和 CA3 的凋亡率明显高于对照组。在肠道中，只有雄性自闭症动物出现了组织病理学变化：结论：产前暴露于 VPA 的雄性和雌性大鼠的脑-肠轴中的炎症和抗氧化因子是一致的。组织病理学后果在暴露于 VPA 的雄性动物中更为显著。

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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.