Induced pluripotent stem cell-derived astrocytes from patients with schizophrenia exhibit an inflammatory phenotype that affects vascularization

Author(s):Show less -

Trindade, Pablo ; Nascimento, Juliana Minardi ; Casas, Barbara S. ; Monteverde, Tomas ; Gasparotto, Juciano ; Ribeiro, Camila Tiefensee ; Devalle, Sylvie ; Sauma, Daniela ; Fonseca Moreira, Jose Claudio ; Gelain, Daniel Pens ; Porciuncula, Lisiane O. ; Palma, Veronica ; Martins-de-Souza, Daniel ; Rehen, Stevens K.

• Document type: Journal article
• Source: MOLECULAR PSYCHIATRY; v. N/A, p. 12-pg., 2022-10-24.

Abstract

Molecular and functional abnormalities of astrocytes have been implicated in the etiology and pathogenesis of schizophrenia (SCZ). In this study, we examined the proteome, inflammatory responses, and secretome effects on vascularization of human induced pluripotent stem cell (hiPSC)-derived astrocytes from patients with SCZ. Proteomic analysis revealed alterations in proteins related to immune function and vascularization. Reduced expression of the nuclear factor kappa B (NF-kappa B) p65 subunit was observed in these astrocytes, with no incremental secretion of cytokines after tumor necrosis factor alpha (TNF-alpha) stimulation. Among inflammatory cytokines, secretion of interleukin (IL)-8 was particularly elevated in SCZ-patient-derived-astrocyte-conditioned medium (A(SCZ)CM). In a chicken chorioallantoic membrane (CAM) assay, A(SCZ)CM reduced the diameter of newly grown vessels. This effect could be mimicked with exogenous addition of IL-8. Taken together, our results suggest that SCZ astrocytes are immunologically dysfunctional and may consequently affect vascularization through secreted factors. (AU)

• FAPESP's process: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/00098-7 - Multi-User Equipment approved in grant 2017/25588-1: cromatógrafo Acquity UPLC I-Class
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/21035-0 - Quantitative proteomics in neural cell lines and organoids derived from induced pluripotent stem cells from schizophrenia patients
• Grantee: Juliana Minardi Nascimento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral