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

Author:

Salari Zahra1,Moslemizadeh Amirhossein2,Tezerji Sara Sheibani3,Sabet Nazanin4,Parizi Ali Saeidpour1,Khaksari Mohammad5,Sheibani Vahid67,Jafari Elham8,Shafieipour Sara1,Bashiri Hamideh67

Affiliation:

1. Gastroenterology and Hepatology Research Center Kerman University of Medical Sciences Kerman Iran

2. Department of Immunology Tehran University of Medical Sciences Tehran Iran

3. Department of Behavioural and Molecular Neurobiology, Regensburg Center for Neuroscience University of Regensburg Regensburg Germany

4. Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman Iran

5. Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences Kerman University of Medical Sciences Kerman Iran

6. Neuroscience Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman Iran

7. Department of Physiology and Pharmacology, Afzalipour School of Medicine Kerman University of Medical Sciences Kerman Iran

8. Pathology and Stem Cells Research Center, Department of Pathology, Afzalipour School of Medicine Kerman University of Medical Science Kerman Iran

Abstract

AbstractIntroductionIn 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.MethodsPregnant 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.ResultsAn 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.ConclusionThe 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.

Funder

Vice Chancellor for Research and Technology, Kerman University of Medical Sciences

Publisher

Wiley

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