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Inducing Plasticity of Astrocytic Receptors by Manipulation of Neuronal Firing Rates
Published on: March 20, 2014
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Assessing Gq-GPCR-induced human astrocyte reactivity using bioengineered neural organoids.
Caroline Cvetkovic1, Rajan Patel2, Arya Shetty1
1Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX.
The Journal of Cell Biology
|February 9, 2022
Summary
Human astrocyte reactivity influences neural network function and immune responses. This study developed a novel bioengineered neural organoid model to investigate astrocyte responses, revealing their impact on neuronal activity and inflammatory pathways.
Area of Science:
- Neuroscience
- Cell Biology
- Stem Cell Research
Background:
- Astrocyte reactivity is crucial in nervous system function, disease, and injury.
- The specific impact of human astrocyte reactivity within neural networks remains unclear.
Purpose of the Study:
- To investigate the consequences of human astrocyte reactivity in a controlled neural network.
- To develop a bioengineered neural organoid model for studying astrocyte-neuron interactions.
Main Methods:
- Utilized transcription factor-driven differentiation of human pluripotent stem cells into neurons and astrocytes.
- Employed genetically encoded tools for dual cell-selective chemogenetic activation.
- Developed a bioengineered neural organoid culture system.
Main Results:
- Gq-GPCR activation in astrocytes led to increased intracellular calcium, immediate early gene induction, and thrombospondin 1 expression.
- Astrocyte activation also triggered NF-κB nuclear translocation and inflammatory protein secretion.
- This astrocyte reactivity correlated with reduced neuronal firing rates in suboptimal conditions, without causing neurotoxicity.
Conclusions:
- Human astrocyte reactivity, when targeting Gq-GPCRs, modulates neuronal activity and inflammatory responses.
- The developed bioengineered neural organoid provides a valuable platform for disease modeling and preclinical drug testing.
