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

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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.

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR PSYCHIATRY; v. N/A, p. 12-pg., 2022-10-24.

Resumo

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)

• Processo FAPESP: 17/25588-1 - Da compreensão básica a biomarcadores clínicos para a esquizofrenia: um estudo multidisciplinar centrado na neuroproteômica
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/00098-7 - EMU concedido no processo 2017/25588-1: cromatógrafo Acquity UPLC I-Class
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 14/21035-0 - Proteômica quantitativa de linhagens neurais e organóides cerebrais derivados de células tronco de pluripotência induzida de pacientes com esquizofrenia
• Beneficiário: Juliana Minardi Nascimento
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado