Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects

International Journal of Molecular Sciences

Karina Griesi-Oliveira¹  Juliana Magdalon¹  Ana Karolyne Santos Gomes¹  Fernanda Mansur¹  Andréa Laurato Sertié¹  André Luiz Teles e Silva¹  Maria Rita Passos-Bueno²  Janaina Sena de Souza³ 

[1] Centro de Pesquisa Experimental, Hospital Israelita Albert Einstein, 05652-900 São Paulo, Brazil;Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, 05508-090 São Paulo, Brazil;Laboratório de Endocrinologia e Medicina Translacional, Departamento de Medicina, Universidade Federal de São Paulo, 04021-001 São Paulo, Brazil;

关键词: complement system;    autism spectrum disorder;    iPSC-derived astrocytes;    complement C4;    synaptic pruning;   

DOI  :  10.3390/ijms22147579

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown