Human-Induced Pluripotent Stem Cell (iPSC)-Derived GABAergic Neuron Differentiation in Bipolar Disorder
Daniel J Schill1, Durga Attili1, Cynthia J DeLong1
1Department of Cell and Developmental Biology, The University of Michigan, Ann Arbor, MI 48109, USA.
Cells
|July 26, 2024
Summary
Bipolar disorder (BP) neurons show altered GABAergic signaling and network activity during development. Understanding these changes in GABAergic interneurons may reveal new therapeutic targets for BP.
Area of Science:
- Neuroscience
- Developmental Biology
- Psychiatry
Background:
- Bipolar disorder (BP) involves mood swings, potentially linked to cortical network imbalances.
- GABAergic interneurons regulate brain excitation/inhibition via chloride transporters NKCC1 and KCC2.
- Dysregulation of these transporters during development may impact cortical structure and function.
Purpose of the Study:
- To investigate GABAergic interneuron development and function in induced pluripotent stem cells (iPSC) from bipolar disorder patients.
- To compare GABAergic signaling and network activity between BP and control neurons.
Main Methods:
- Derived iPSCs from BP patients and controls.
- Differentiated iPSCs into GABAergic interneurons at sequential stages.
- Utilized qRT-PCR, RNA sequencing, and multi-electrode array (MEA) analysis.
Main Results:
- BP neurons exhibited increased firing rates and network bursting.
- BP neurons showed decreased synchrony compared to controls.
- Controls transiently expressed high NKCC1 levels during differentiation.
Conclusions:
- Altered GABAergic signaling and network activity are observed in BP neurons.
- Developmental perturbations in NKCC1/KCC2 may contribute to BP pathophysiology.
- GABA signaling during interneuron differentiation presents potential therapeutic targets for BP.
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