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

Salari, Zahra and Moslemizadeh, Amirhossein and Sheibani-Tezerji, Sara and Sabet, Nazanin and Parizi, Ali Saeidpour and Khaksari, Mohammad and Sheibani, Vahid and Jafari, Elham and Shafieipour, Sara and Bashiri, Hamideh (2024) Sex-dependent alterations of inflammatory factors, oxidative stress, and histopathology of the brain-gut axis in a VPA-induced autistic-like model of rats. BIRTH DEFECTS RESEARCH, 116 (4): e2310. ISSN 2472-1727

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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-1 beta (IL-1 beta) 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.

Item Type: Article
Uncontrolled Keywords: VALPROIC ACID; SPECTRUM DISORDERS; ANTIEPILEPTIC DRUGS; ANTIOXIDANT ENZYMES; LIPID-PEROXIDATION; CYTOKINE LEVELS; MOUSE MODELS; SERUM-LEVELS; CHILDREN; BIOMARKERS; autism; inflammation; intestine; oxidative stress; valproic acid
Subjects: 500 Science > 570 Life sciences
500 Science > 590 Zoological sciences
Divisions: Biology, Preclinical Medicine > Institut für Zoologie
Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 13 Jan 2026 09:22
Last Modified: 13 Jan 2026 09:22
URI: https://pred.uni-regensburg.de/id/eprint/65102

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