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

Autor(es)

Mansur, Fernanda ^[1] ; Teles e Silva, Andre Luiz ^[1] ; Santos Gomes, Ana Karolyne ^[1] ; Magdalon, Juliana ^{[1, 2]} ; de Souza, Janaina Sena ^[3] ; Griesi-Oliveira, Karina ^[1] ; Passos-Bueno, Maria Rita ^[4] ; Sertie, Andrea Laurato ^[1]

Afiliação do(s) autor(es)

^[1] Hosp Israelita Albert Einstein, Ctr Pesquisa Expt, BR-05652900 Sao Paulo - Brazil

^[2] Fac Israelita Ciencias Saude Albert Einstein, BR-05521200 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Med, Lab Endocrinol & Med Translac, BR-04021001 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, BR-05508090 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 14 JUL 2021.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 15/50138-4 - Investigação do papel do sistema do complemento no desenvolvimento cerebral e nos Transtornos do Espectro Autista
• Beneficiário: Andréa Laurato Sertié
• Modalidade de apoio: Auxílio à Pesquisa - Regular