LPS Exposure Increases Maternal Corticosterone Levels, Causes Placental Injury and Increases IL-1B Levels in Adult Rat Offspring: Relevance to Autism

Autor(es)

Kirsten, Thiago B. ^[1] ; Lippi, Luciana L. ^[1] ; Bevilacqua, Estela ^[2] ; Bernardi, Maria M. ^{[3, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Vet Med, Dept Pathol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil

^[3] Univ Paulista, Grad Program Environm & Expt Pathol, Sao Paulo - Brazil

^[4] Univ Paulista, Grad Program Dent, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 12 DEC 2 2013.
• Citações Web of Science: 40

Resumo

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 mu g/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-1 beta serum levels, revealing that prenatal LPS exposure modified the immune response to a LPS challenge in adulthood. Increased IL-1 beta 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. (AU)

• Processo FAPESP: 08/53861-5 - Efeitos comportamentais, imunes e moleculares da administração pré-natal de lipopolissacarídeo na prole masculina de ratas
• Beneficiário: Thiago Berti Kirsten
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/51886-3 - Neuroimunomodulação: fármacos, estresse e citocinas nas relações entre os sistemas nervoso, endócrino e imune
• Beneficiário: João Palermo Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/07007-8 - Possível prevenção ou tratamento dos prejuízos induzidos pela exposição no início da gestação ao lipopolissacarídeo em um modelo experimental de autismo
• Beneficiário: Thiago Berti Kirsten
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado