Mayo Clinic and Yale University scientists have used a mini-brain model to reveal the link to autism spectrum disorder.
The human mini-brain models, known as organoids, have found out that the roots of autism spectrum disorder may be associated with an imbalance of specific neurons that play a vital role in how the brain communicates and functions.
The cells that are specifically affected are called excitatory cortical neurons.
The study, ‘Modelling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis,’ is published in Nature Neuroscience.
What is autism spectrum disorder?
Autism spectrum disorder is a neurological condition that impacts the way people perceive and interact with others. This can lead to challenges in social communication and behaviour.
The term spectrum is used to demonstrate the range of symptoms and severity, and includes autism, Asperger’s syndrome, childhood disintegrative disorder, and an unspecified form of pervasive developmental disorder.
According to estimates from the Centres for Disease Control’s Autism and Developmental Disabilities Monitoring Network, almost one in 36 children in the US have been identified with autism spectrum disorder.
An imbalance of neurons was found in people with autism
The team discovered an abnormal imbalance of excitatory neurons in the forebrain of people with the disorder, depending on their head size.
“This organoid technology allowed us to recreate the brain development alteration that happened in the patients when they were in the uterus, which is believed to be the time when autism spectrum disorder originates,” said Alexej Abyzov, PhD, a genomic researcher in the Department of Quantitative Health Sciences at the Mayo Clinic Centre for Individualised Medicine.
Mini-brains were used for the study
The scientists used and created 3D brain-like models, called organoids. The pea-sized clusters of cells began as skin cells from people with autism.
These cells were placed in a culture dish and reprogrammed back into a stem-cell-like-state. These are called induced pluripotent stem cells or master cells. They can be coaxed to develop into any cell in the body – even brain cells.
The scientists then used a special technology, single-cell RNA sequencing, to explore the gene expression patterns of individual brain cells. In total, 664,272 brains were examined at three different stages of brain development.
It was also found that the neuron imbalance resulted from changes in the activity of certain genes known as transcription factors.
These play a vital role in directing the development of cells during the initial stages of brain formation.
The study built upon previous evidence
The study builds on 13 years of published studies on autism spectrum disorder by Dr Abyzov and his collaborators.
In one study, they showed molecular differences in organoids between people with autism and those without. They found that the deregulation of a specific transcription factor called FOXG1 was an underlying cause of the disorder.
“Autism is mostly a genetic disease. Our goal is to be able to determine the risk of autism spectrum disorder and possibly prevent it in an unborn child using prenatal genetic testing. However, this would require detailed knowledge of how brain regulation gets derailed during development. There are many aspects in which organoids could help in this direction,” concluded Dr Abyzov.
