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Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects.
Mansur, Fernanda; Teles E Silva, André Luiz; Gomes, Ana Karolyne Santos; Magdalon, Juliana; de Souza, Janaina Sena; Griesi-Oliveira, Karina; Passos-Bueno, Maria Rita; Sertié, Andréa Laurato.
Afiliação
  • Mansur F; Centro de Pesquisa Experimental, Hospital Israelita Albert Einstein, 05652-900 São Paulo, Brazil.
  • Teles E Silva AL; Centro de Pesquisa Experimental, Hospital Israelita Albert Einstein, 05652-900 São Paulo, Brazil.
  • Gomes AKS; Centro de Pesquisa Experimental, Hospital Israelita Albert Einstein, 05652-900 São Paulo, Brazil.
  • Magdalon J; Centro de Pesquisa Experimental, Hospital Israelita Albert Einstein, 05652-900 São Paulo, Brazil.
  • de Souza JS; Faculdade Israelita de Ciências da Saúde Albert Einstein, 05521-200 São Paulo, Brazil.
  • Griesi-Oliveira K; Laboratório de Endocrinologia e Medicina Translacional, Departamento de Medicina, Universidade Federal de São Paulo, 04021-001 São Paulo, Brazil.
  • Passos-Bueno MR; Centro de Pesquisa Experimental, Hospital Israelita Albert Einstein, 05652-900 São Paulo, Brazil.
  • Sertié AL; Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, 05508-090 São Paulo, Brazil.
Int J Mol Sci ; 22(14)2021 Jul 15.
Article em En | MEDLINE | ID: mdl-34299197
In recent years, accumulating evidence has shown that the innate immune complement system is involved in several aspects of normal brain development and in neurodevelopmental disorders, including autism spectrum disorder (ASD). Although abnormal expression of complement components was observed in post-mortem brain samples from individuals with ASD, little is known about the expression patterns of complement molecules in distinct cell types in the developing autistic brain. In the present study, we characterized the mRNA and protein expression profiles of a wide range of complement system components, receptors and regulators in induced pluripotent stem cell (iPSC)-derived neural progenitor cells, neurons and astrocytes of individuals with ASD and neurotypical controls, which constitute in vitro cellular models that recapitulate certain features of both human brain development and ASD pathophysiology. We observed that all the analyzed cell lines constitutively express several key complement molecules. Interestingly, using different quantification strategies, we found that complement C4 mRNA and protein are expressed in significantly lower levels by astrocytes derived from ASD individuals compared to control astrocytes. As astrocytes participate in synapse elimination, and diminished C4 levels have been linked to defective synaptic pruning, our findings may contribute to an increased understanding of the atypically enhanced brain connectivity in ASD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Complemento C4 / Astrócitos / Células-Tronco Pluripotentes Induzidas / Células-Tronco Neurais / Transtorno do Espectro Autista / Neurônios Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Complemento C4 / Astrócitos / Células-Tronco Pluripotentes Induzidas / Células-Tronco Neurais / Transtorno do Espectro Autista / Neurônios Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça