Altered Neuronal Support and Inflammatory Response in Bipolar Disorder Patient-Derived Astrocytes.
Stem Cell Reports
; 16(4): 825-835, 2021 04 13.
Article
em En
| MEDLINE
| ID: mdl-33667413
ABSTRACT
Bipolar disorder (BD) is characterized by cyclical mood shifts. Studies indicate that BD patients have a peripheral pro-inflammatory state and alterations in glial populations in the brain. We utilized an in vitro model to study inflammation-related phenotypes of astrocytes derived from induced pluripotent stem cells (iPSCs) generated from BD patients and healthy controls. BD astrocytes showed changes in transcriptome and induced a reduction in neuronal activity when co-cultured with neurons. IL-1ß-stimulated BD astrocytes displayed a unique inflammatory gene expression signature and increased secretion of IL-6. Conditioned medium from stimulated BD astrocytes reduced neuronal activity, and this effect was partially blocked by IL-6 inactivating antibody. Our results suggest that BD astrocytes are functionally less supportive of neuronal excitability and this effect is partially mediated by IL-6. We confirmed higher IL-6 in blood in a distinct cohort of BD patients, highlighting the potential role of astrocyte-mediated inflammatory signaling in BD neuropathology.
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Base de dados:
MEDLINE
Assunto principal:
Transtorno Bipolar
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Astrócitos
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Inflamação
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Neurônios
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article