Lipopolysaccharide Exposure Induces Maternal Hypozincemia, and Prenatal Zinc Treatment Prevents Autistic-Like Behaviors and Disturbances in the Striatal Dopaminergic and mTOR Systems of Offspring

Autor(es)

Kirsten, Thiago Berti ^{[1, 2]} ; Chaves-Kirsten, Gabriela P. ^[3] ; Bernardes, Suene ^[4] ; Scavone, Cristoforo ^[3] ; Sarkis, Jorge E. ^[5] ; Bernardi, Maria Martha ^[2] ; Felicio, Luciano F. ^[1]

Afiliação do(s) autor(es)

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

^[2] Univ Paulista, Environm & Expt Pathol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Phys, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Energy & Nucl Res IPEN, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 7 JUL 28 2015.
• Citações Web of Science: 16

Resumo

Autism is characterized by social deficits, repetitive behaviors, and cognitive inflexibility. The risk factors appear to include genetic and environmental conditions, such as prenatal infections and maternal dietary factors. Previous investigations by our group have demonstrated that prenatal exposure to lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria, induces autistic-like behaviors. To understand the causes of autistic-like behaviors, we evaluated maternal serum metal concentrations, which are involved in intrauterine development and infection/inflammation. We identified reduced maternal levels of zinc, magnesium, selenium and manganese after LPS exposure. Because LPS induced maternal hypozincemia, we treated dams with zinc in an attempt to prevent or ease the impairments in the offspring. We evaluated the social and cognitive autistic-like behaviors and brain tissues of the offspring to identify the central mechanism that triggers the development of autism. Prenatal LPS exposure impaired play behaviors and T-maze spontaneous alternations, i.e., it induced autistic-like behaviors. Prenatal LPS also decreased tyrosine hydroxylase levels and increased the levels of mammalian target of rapamycin (mTOR) in the striatum. Thus, striatal dopaminergic impairments may be related to autism. Moreover, excessive signaling through the mTOR pathway has been considered a biomarker of autism, corroborating our rat model of autism. Prenatal zinc treatment prevented these autistic-like behaviors and striatal dopaminergic and mTOR disturbances in the offspring induced by LPS exposure. The present findings revealed a possible relation between maternal hypozincemia during gestation and the onset of autism. Furthermore, prenatal zinc administration appears to have a beneficial effect on the prevention of autism. (AU)

• 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
• Processo FAPESP: 13/01610-7 - Subsistência e reprodução: modulação opioidérgica de comportamentos durante a lactação
• Beneficiário: Luciano Freitas Felicio
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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