Modeling Autism Using Stem Cells

in Reporting from the Lab by

Autism spectrum disorder (ASD) is a complex neuropsychiatric disorder associated with impaired communication and social interaction. Since several genetic and environmental factors contribute to the pathology of ASD, developing a model system to study ASD is extremely difficult. In a recent report published in the journal Biological Psychiatry, researchers at the University of São Paulo, Brazil and the University of California, San Diego used induced pluripotent stem cells (iPSCs) for modeling ASD. iPSCs are generated by reprogramming of mature differentiated cells of the body into embryonic-like cells. iPSCs, therefore, can generate all the cell types found in the body.

For this study, researchers generated iPSCs from dental pulp cells of the teeth donated by three children diagnosed with ASD as well as their age-matched controls. The generated iPSCs were then used to derive neurons and astrocytes, the two major cell types found in the brain. The neurons derived from ASD patients formed a lesser number of connections and showed reduced firing rates as compared to the healthy neurons. In this study, researchers showed for the first time the involvement of astrocytes in the pathology of ASD, using iPSCs as a model. When the neurons derived from ASD patients were cultured with healthy astrocytes, they showed an improvement in their morphology. On the other hand, the culture of healthy neurons with ASD-derived astrocytes hindered neuronal development.

The researchers made an interesting observation that ASD-derived astrocytes produced higher levels of IL-6, a proinflammatory protein, as compared to the healthy astrocytes. Additionally, blocking IL-6 improved the connectivity of ASD-derived neurons, whereas addition of IL-6 to healthy neurons impaired their connectivity. This finding suggests that controlling IL-6 levels might prove to be beneficial for the treatment of ASD. However, further experiments are required to confirm this finding. Taken together, this study provides interesting insights on the biological basis of ASD, by identifying a critical role of astrocytes in this disorder, which may help to develop novel therapies for its treatment.

Journal reference:

Russo FB, Freitas BC, Pignatari GC, Fernandes IR, Sebat J, Muotri AR, Beltrão-Braga PCB. Modeling the interplay between neurons and astrocytes in autism using human induced pluripotent stem cells. Biol Psychiatry. 2017 Oct 3. pii: S0006-3223(17)32009-7. doi: 10.1016/j.biopsych.2017.09.021.

Other references:

https://www.elsevier.com/about/press-releases/research-and-journals/induced-pluripotent-stem-cells-reveal-astrocyteneuron-interplay-contributes-to-brain-pathology-in-autism

https://www.sciencedaily.com/releases/2017/10/171018190857.htm

https://www.biotechniques.com/news/Neurobiologys-Model-Revolution/biotechniques-366492.html

https://www.hindawi.com/journals/sci/2016/7909176Pixabay/

http://dmm.biologists.org/content/5/1/26

Featured image source: Pixabay

About the author:

Isha Verma has finished her Ph.D. from the Indian Institute of Science, Bangalore. Her research work focussed on the generation and characterization of neural cells from stem cells. She is currently looking for postdoctoral research position.  She also works as a freelance scientific editor and scientific consultant. She loves reading, traveling, and stargazing. She can be reached here.

Edited by: Radhika Raheja

Isha Verma is currently working at the Indian Institute of Science, Bangalore. Her research work focusses on 'developing novel strategies for efficient differentiation of mouse pluripotent stem cells into neural lineage'.

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