A comparative study of the impact of maternal immune activation and valproic acid on autism-like behavior in rats.

Abstract

Objectives: The present study aimed to evaluate the behavioral consequences of maternal immune activation (MIA) induced by lipopolysaccharide (LPS), in comparison to valproic acid (VPA), a widely used and reliable inducer of autism-like features in rats when administered during prenatal development. At the behavioral level, we further assessed the potential ameliorative effects of a standardized polyphenol-rich extract derived from the leaves of Cynara cardunculus L. (artichoke), used as a prebiotic - either independently or in combination with a probiotic mixture and/or omega-3 (ω3) fatty acids.

Methods: Wistar albino rats prenatally exposed to LPS or VPA were evaluated for social behavior using the three-chamber social interaction test. Beginning at 7 days of age, male rat pups received specific doses of the artichoke as prebiotic (AR), probiotics (Pro), and ω3 supplements, depending on group assignment. A total of 54 neonatal male rats were divided into nine experimental groups: (1) Control group: received normal saline; (2) VPA-0 group: prenatally exposed to VPA only; (3) VPA-AR group: prenatally exposed to VPA, postnatally treated with AR; (4) VPA-AR.Pro group: prenatally exposed to VPA, postnatally treated with AR + Pro; (5) VPA.AR-AR group: received AR during gestation (protectively), and postnatal AR after VPA exposure; (6) LPS-0 group: prenatally exposed to LPS only; (7) LPS-AR group: prenatally exposed to LPS, postnatally treated with AR; (8) LPS-AR.Pro.ω3 group: prenatally exposed to LPS, postnatally treated with AR + Pro + ω3; (9) LPS.AR-AR group: received AR during gestation (protectively), and postnatal AR after LPS exposure.

Results: LPS and prenatal VPA exposure significantly impair social interactions and promoting stereotypic-like behaviors. Notably, both pre- and postnatal administration of artichoke extract demonstrated significant potential in improving these behavioral deficits. MIA and prenatal VPA exposure have detrimental effects on neurobehavioral development, particularly impairing social interactions and promoting stereotypic-like behaviors consistent with ASD.

Conclusions: These results provide evidence for the beneficial role of artichoke-derived prebiotics, alone or in combination with probiotics and ω3, in improving ASD-like symptoms in rodent models of autism.