Related Experiment Video
Updated: Aug 5, 2026
04:42
Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
The Toll-Like Receptor Signalling Pathway Is Altered in iPSC-Derived Cortical Networks From People With Bipolar
Bruna Panizzutti1, Chiara Cristina Bortolasci1,2, Megan Ellis1
1School of Medicine, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Bipolar Disorders
|August 4, 2026
Summary
Induced pluripotent stem cell-derived brain cells reveal immune system dysregulation in bipolar disorder (BD). Key innate immune pathways are downregulated, suggesting a complex signaling network role in BD pathophysiology.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Induced pluripotent stem cells (iPSCs) offer a model for studying neuropsychiatric disorders by retaining donor genetics.
- Cortical networks derived from iPSCs allow in vitro study of living human brain cells.
Purpose of the Study:
- To identify molecular mechanisms underlying bipolar disorder (BD) pathophysiology.
- To investigate differences in gene expression in brain cells from individuals with and without BD.
Main Methods:
- Generated iPSCs from peripheral blood mononuclear cells (PBMCs).
- Differentiated iPSCs into cortical networks (CNs).
- Performed whole transcriptome sequencing and differential expression analysis.
Main Results:
- Identified 191 enriched pathways in BD, with 171 downregulated.
- Approximately 10% of enriched pathways were associated with the immune system.
- The toll-like signaling pathway was found to be downregulated in BD.
Conclusions:
- Suggests profound immune dysregulation in bipolar disorder.
- Highlights downregulation of the sensing innate immune system in BD.
- Emphasizes the immune system's role as a complex signaling network in BD.
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