Autism is a neurodevelopmental condition that researchers are now tracing back to prenatal development, even though the disorder is not diagnosed until at least 18 months of age.
In a new study, researchers found in human brain cells that the atypical development starts at the very earliest stages of brain organization, at the level of individual brain cells.
They used induced pluripotent stem cells, or iPSCs, to model early brain development.
The findings indicate that brain cells from autistic people develop differently from those from typical individuals.
The study is from scientists at King’s College London and Cambridge University, UK.
In the study, the researchers isolated hair samples from nine autistic people and six typical people.
By treating the cells with an array of growth factors, the scientists were able to drive the hair cells to become nerve cells or neurons—much like those found in either the cortex or the midbrain region.
iPSCs retain the genetic identity of the person from which they came and the cells re-start their development as it would have happened in the womb, providing a window into that person’s brain development.
At various stages, the team examined the developing cells’ appearance and sequenced their RNA, to see which genes the cells were expressing.
At day 9, developing neurons from typical people formed “neural rosettes,” an intricate, dandelion-like shape indicative of typically developing neurons.
Cells from autistic people formed smaller rosettes or did not form rosettes at all. And key developmental genes were expressed at lower levels in cells from autistic people.
At days 21 and 35, the cells from typical and autistic people differed significantly in a number of ways, suggesting that the makeup of neurons in the cortex differs in the autistic and typically developing brain.
The team says the emergence of differences associated with autism in these nerve cells shows that these differences arise very early in life.
In contrast to the differences seen in cortical neurons, cells directed to develop as midbrain neurons—a brain region not implicated in autism dysfunction—showed only negligible differences between typical and autistic people.
The team says such findings will lead to a better understanding of brain development in both autistic and typical individuals.
One author of the study is Deepak Srivastava, Ph.D.
The study is published in Biological Psychiatry.
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