Preventive effects of resveratrol against early-life impairments in the animal model of autism induced by valproic acid

Gustavo Brum Schwingel; Mellanie Fontes-Dutra; Bárbara Ramos; Rudimar Riesgo; Victorio Bambini-Junior; Carmem Gottfried

doi:10.1016/j.ibneur.2023.09.008

Preventive effects of resveratrol against early-life impairments in the animal model of autism induced by valproic acid

IBRO Neurosci Rep. 2023 Sep 23:15:242-251. doi: 10.1016/j.ibneur.2023.09.008. eCollection 2023 Dec.

Authors

Gustavo Brum Schwingel^{1

2

3

4}, Mellanie Fontes-Dutra^{1

2

3

4}, Bárbara Ramos^{1

2}, Rudimar Riesgo^{1

3

4

5}, Victorio Bambini-Junior^{3

4

6}, Carmem Gottfried^{1

2

3

4}

Affiliations

¹ Translational Research Group in Autism Spectrum Disorders-GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
² Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
³ National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Brazil.
⁴ Autism Wellbeing and Research Development (AWARD) Initiative, BR-UK-CA, Brazil.
⁵ Child Neurology Unit, Hospital de Clínicas de Porto Alegre (HCPA), Brazil.
⁶ Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, United Kingdom.

Abstract

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social interaction deficits and repetitive/stereotyped behaviors. Its prevalence is increasing, affecting one in 36 children in the United States. The valproic acid (VPA) induced animal model of ASD is a reliable method for investigating cellular, molecular, and behavioral aspects related to the disorder. Trans-Resveratrol (RSV), a polyphenol with anti-inflammatory and antioxidant effects studied in various diseases, has recently demonstrated the ability to prevent cellular, molecular, sensory, and social deficits in the VPA model. In this study, we examined the effects of prenatal exposure to VPA and the potential preventive effects of RSV on the offspring.

Method: We monitored gestational weight from embryonic day 6.5 until 18.5 and assessed the onset of developmental milestones and morphometric parameters in litters. The generalized estimating equations (GEE) were used to analyze longitudinal data.

Results: Exposure to VPA during rat pregnancy resulted in abnormal weight gain fold-changes on embryonic days 13.5 and 18.5, followed by fewer animals per litter. Additionally, we discovered a positive correlation between weight variation during E15.5-E18.5 and the number of rat pups in the VPA group.

Conclusion: VPA exposure led to slight length deficiencies and delays in the onset of developmental milestones. Interestingly, the prenatal RSV treatment not only prevented most of these delays but also led to the early onset of certain milestones and improved morphometric characteristics in the offspring. In summary, our findings suggest that RSV may have potential as a therapeutic intervention to protect against the negative effects of prenatal VPA exposure, highlighting its importance in future studies of prenatal neurodevelopmental disorders.

Keywords: Animal model; Autism; Milestones; Morphometric parameters; Rat; Resveratrol; Rodent; VPA.