Exposição pré-natal ao lipopolissacarídeo promove comportamento tipo-autista na prole: participação de moduladores inflamatórios

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder of unknown etiology that affects 1% of the population and is more common in men. Characterized by deficits in communication, social interaction, risk assessment, in addition to repetitive and stereotyped behaviors, and restricted interest in objects and subjects. In the present study, we investigated through the animal model whether prenatal infections could be the cause of autistic-like behaviors. The proposed model aimed to mimic infections in rats during pregnancy through the application of lipopolysaccharide (LPS) intraperitoneally (i.p.). Concomitantly with LPS, non-steroidal or steroidal anti- inflammatory drugs were applied i.p. to prevent symptoms caused by LPS. The present study was divided into two parts, where first the rats were treated with LPS and anti- inflammatory, and 2 and 6 hours later they underwent behavioral tests, and soon after they were euthanized for collection of maternal plasma, fetal brain and amniotic fluid where cytokines TNF-α, IL-6 and IL-1β and placenta where the expression of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) was quantified. In a second moment, another group of pregnant rats were treated in the same way as the previous ones and the birth of the pups was awaited. These pups were weighed and their litters standardized into 4 males and 4 females. Male pups underwent behavioral testing during pre-pubertal, puberty and adulthood. LPS applied during pregnancy caused sickness behavior in the rats and caused abortions. In addition, male pups showed autistic-like behaviors such as deficits in communication and social interaction, anxious-like behavior and increased autonomic response, as evidenced by the elevation of blood pressure during a restraint stress test. The non-steroidal anti- inflammatory prevented some of the symptoms of unhealthy behavior in the rats but did not reduce abortions, but it did prevent some autistic-like behavior in the offspring. The steroidal anti-inflammatory, on the other hand, prevented the symptoms of sickness behavior and abortions, however it provoked autistic-like behavior in the pups in the same way as LPS.