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Altered neuronal support and inflammatory response in bipolar disorder patient-derived astrocytes

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-1b-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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Submitted on : Monday, March 8, 2021 - 10:52:03 AM
Last modification on : Thursday, April 7, 2022 - 1:58:19 PM
Long-term archiving on: : Wednesday, June 9, 2021 - 6:36:29 PM


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Krishna C Vadodaria, Ana P D Mendes, Arianna Mei, Vipula Racha, Galina Erikson, et al.. Altered neuronal support and inflammatory response in bipolar disorder patient-derived astrocytes. Current Stem Cell Reports, Springer, 2021, pp.S2213-6711(21)00084-9. ⟨10.1016/j.stemcr.2021.02.004⟩. ⟨inserm-03161941⟩



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