Autism is a neurodevelopmental condition that isn’t diagnosed until at least 18 months of age. A new study now is tracing back to prenatal development, to understand if the disease development starts at very early stages of brain organization. The study from scientists at King’s College London and Cambridge University, UK appears in Biological Psychiatry, published by Elsevier. The study used induced pluripotent stem cells, or iPSCs, to model early brain development. The findings indicate that brain cells from autistic people develop differently to those from others.
The researchers isolated hair samples from nine autistic people and six people from the general population. By treating the cells with an array of growth factors, the scientists drove the hair cells to become nerve cells, or neurons, very similar to those found in either the cortex or the midbrain region. iPSCs retain the genetic identity of the person from which they came and therefore the cells re-start their development as it would have happened within the womb, providing a window into that person’s brain development.
According to the researchers, using iPSCs from hair samples was one of the best ways to study early brain development in autistic people. Benefits include the fact that it bypasses the necessity for animal research, it is non-invasive, and requires just one hair or skin sample from an individual.
The developing cells’ appearance was examined at different points, and their RNA were sequenced, to observe which genes the cells were expressing. The developing neurons from typical people formed “neural rosettes,” an intricate, dandelion-like shape indicative of typically developing neurons, by day 9. Cells from autistic people formed smaller rosettes or no rosettes at all. And some key developmental genes were expressed at a much lower level in cells from autistic people.
At days 21 and 35, the cells from the subjects of both the categories differed significantly, suggesting that the makeup of neurons within the cortex differs in the two categories. This helped in concluding the fact that the emergence of differences related to autism in these nerve cells shows that these differences arise very early in life. Another notable finding was that the midbrain neurons, a brain region not involved in autism dysfunction, showed only negligible differences between typical and autistic people.
The use of iPSCs helped in identifying precisely the differences in cell fates and gene pathways that occur in neural cells from autistic and typical individuals. These findings will hopefully contribute to our understanding of why there’s such diversity in brain development. The nerve cells derived from peripheral stem cells in this study was in fact used as a tool for a better understanding of the disease than trying to ‘prevent,’ ‘eradicate,’ or ‘cure’ autism.
References:
- Biological Psychiatry, 2020; DOI: 10.1016/j.biopsych.2020.06.014,
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