Altered Neuronal Support and Inflammatory Response in Bipolar Disorder Patient-Derived Astrocytes

Stem Cell Reports. 2021 Apr 13;16(4):825-835. doi: 10.1016/j.stemcr.2021.02.004. Epub 2021 Mar 4.


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-1β-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.

Keywords: IL-6; astrocytes; cytokine; glia; iPSC; inflammation; mood disorders; neuronal activity; psychiatry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Astrocytes / pathology*
  • Bipolar Disorder / pathology*
  • Coculture Techniques
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / pathology
  • Inflammation / pathology*
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / metabolism
  • Neuroglia / drug effects
  • Neuroglia / pathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology*


  • Interleukin-1beta
  • Interleukin-6