title: LPS exposure increases maternal corticosterone levels, causes placental injury and increases IL-1Β levels in adult rat offspring: relevance to autism.
abstract: Maternal immune activation can induce neuropsychiatric disorders, such as autism and schizophrenia. Previous investigations by our group have shown that prenatal treatment of rats on gestation day 9.5 with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally), which mimics infections by gram-negative bacteria, induced autism-like behavior in male rats, including impaired communication and socialization and induced repetitive/restricted behavior. However, the behavior of female rats was unchanged. Little is known about how LPS-induced changes in the pregnant dam subsequently affect the developing fetus and the fetal immune system. The present study evaluated the hypothalamic-pituitary-adrenal (HPA) axis activity, the placental tissue and the reproductive performance of pregnant Wistar rats exposed to LPS. In the adult offspring, we evaluated the HPA axis and pro-inflammatory cytokine levels with or without a LPS challenge. LPS exposure increased maternal serum corticosterone levels, injured placental tissue and led to higher post-implantation loss, resulting in fewer live fetuses. The HPA axis was not affected in adult offspring. However, prenatal LPS exposure increased IL-1β serum levels, revealing that prenatal LPS exposure modified the immune response to a LPS challenge in adulthood. Increased IL-1β levels have been reported in several autistic patients. Together with our previous studies, our model induced autistic-like behavioral and immune disturbances in childhood and adulthood, indicating that it is a robust rat model of autism.
authors: Department of Pathology, School of Veterinary Medicine, University of São Paulo, Sao Paulo, São Paulo, Brazil.
authors: Thiago B
authors: TB
authors: Kirsten
authors: Luciana L
authors: LL
authors: Lippi
authors: Estela
authors: E
authors: Bevilacqua
authors: Maria M
authors: MM
authors: Bernardi
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000097:blood; D003345:Corticosterone / Q000097:blood*; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010920:Placenta / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D051381:Rats
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D003345:Corticosterone