Transmission of behavioral and cognitive impairments across generations in rats subjected to prenatal valproic acid exposure.

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) represents an inheritable neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Numerous studies have underscored the significant roles played by genetic and environmental factors in the etiology of ASD, and these factors are known to perpetuate behavioral impairments across generations. OBJECTIVES: The primary objective of this study was to assess the behavioral and cognitive attributes in the second filial (F2) generation of male and female rats, with a particular focus on those whose parents had been exposed to valproic acid (VPA) during embryonic development. METHODS: In this study, a cohort of 32 male and 32 female rats from the second filial (F2) generation, referred to as Mother.ASD, Father.ASD, or Both.ASD, was examined. These designations indicate whether the mother, father, or both parents had experienced embryonic exposure to valproic acid (600 mg/kg, i.p.). During adolescence, the F2 pups underwent behavioral and cognitive assessments, including open field testing, marble burying, social interaction evaluations, and Morris water maze tasks. RESULTS: Our data revealed that while both the Mother.ASD and Father.ASD groups, regardless of sex, exhibited elevated anxiety-like behavior in the open field test. Only the Mother.ASD group displayed repetitive behaviors and deficits in social memory. Additionally, spatial memory impairments were observed in both sexes. These findings highlight the transmission of autistic-like behaviors in the offspring of Mother.ASD rats from both sexes. Nevertheless, future research endeavors should be more targeted in identifying the specific genes responsible for this transmission. CONCLUSION: In summary, our findings underscore the transmission of autistic-like behaviors, including anxiety-like behavior, repetitive actions, impairments in social interactions, and deficits in memory, to the offspring of the Mother.ASD group, irrespective of their sex.