A new study published in Nature Communications delves further into autism by growing brain-like organoids.
“The human brain is unique, and certain aspects of human brain development and brain disease are notoriously difficult to study using animal models,” said study author Alex Shegrovitov. “We wanted to develop a new method to model the early stages of human telencephalic brain development in health and disease. Our approach is robust and reproducible,” said Dr. The method was to make human brain organoids.”
The researchers had the idea to start with pluripotent stem cell-derived neural rosettes.
“These are beautifully self-organized clusters of neural progenitor cells that may improve the cellular organization of brain organoids,” Shcheglovitov said. “We wanted to apply this model to the study of neurodevelopmental disorders.”
Genetic abnormalities in a gene called SHANK3 cause autism and other neurodevelopmental disorders. To study these defects, researchers created organoids from cells with the same genetic abnormalities.
“To study the human brain, we need reliable models,” Shcheglovitov said. “We also wanted to use human and patient-specific cells to develop a methodology to understand the cellular and molecular mechanisms disrupted in human brain injury. We plan to use it to develop new treatments for those patients.”
Researchers differentiated human pluripotent stem cells into structures called neural rosettes. Single rosettes were then manually isolated and cultured for up to 5 months to create organoids. They also generated organoids from stem cells obtained from healthy controls and patients with mutations in the gene SHANK3.
“We found that organoids made in this way consisted of diverse cells that were organized relative to each other, similar to how they are organized in the brain,” said Shcheglovitov. rice field. “We found that many neurons in organoids mature functionally.”
The researchers also found that organoids lacking the gene SHANK3 had synaptic and intrinsic defects associated with perturbed expression of the clustered protocadherin, a cell adhesion protein.
“I was very impressed with the finding of the majority of inhibitory neurons in organoids from single neural rosettes and in ependymal and endothelial-like cells that, to my knowledge, have never been observed in organoids before. I was surprised, ”said Shcheglovitov. “These cells are important for making the brain an isolated organ in the body.
Of course, the perturbed expression of clustered protocadherins in SHANK3-deficient organoids is of great interest. It may explain some of the observed deficits associated with SHANK3 deficiency, and this knowledge may contribute to the development of new treatments for patients. However, more work needs to be done on this front. “
The results of this study provide insight into human telencephalic development and disorders associated with SHANK3 deficiency, including Phelan-McDermid syndrome, autism, intellectual disability, and epilepsy. This is an important step in our ability to model human brain development in health and disease, and may aid future drug development. is important.
Patricia Tomasi is a mother, maternal mental health advocate, journalist and speaker. She is a regular contributor to The Huffington Post Her Canada, mostly focusing on the mental health of her mother, who twice suffered from severe postpartum anxiety. Her Huffington Post biography can be found here. Patricia is also a North American-based patient expert in the Mental Health Research Group. Support Group). Her blog: www.patriciatomasiblog.wordpress.com