Scientists from Mayo Clinic and Yale University have made an important discovery that may help explain how autism spectrum disorder begins in the very early stages of brain development.
By using tiny lab-grown versions of the human brain, researchers were able to watch how brain cells grow and organize themselves, and they discovered a key difference in the brains of people with autism.
Autism spectrum disorder, often called ASD, is a condition that affects how people communicate, interact with others, and behave. It is called a “spectrum” because the condition can appear in many different ways.
Some people with autism may have difficulty speaking or understanding social situations, while others may have strong talents, deep interests in certain topics, or unique ways of thinking.
According to the U.S. Centers for Disease Control and Prevention, about 1 in every 36 children in the United States is diagnosed with autism today. Scientists have been trying for many years to understand exactly how autism develops in the brain.
In the new study, researchers used tiny brain-like structures known as organoids. These are sometimes called “mini-brains.” They are not real brains and cannot think or feel, but they grow in a way that closely copies how the human brain develops during pregnancy.
Scientists create these mini-brains from human cells in the laboratory so they can observe the earliest stages of brain development, something that cannot be studied directly in unborn babies.
To create these models, the researchers started with skin cells from people with and without autism. The skin cells were then changed into special cells that behave like stem cells. Stem cells have the remarkable ability to develop into almost any type of cell in the body.
In this case, the scientists guided them to become brain cells and allowed them to grow into tiny three-dimensional brain structures that resemble the early human forebrain.
The forebrain is one of the most important parts of the brain. It is responsible for many complex functions such as thinking, memory, emotions, and decision-making. Because of its role in communication and behavior, scientists believe that differences in this region may play a major role in autism.
When the researchers studied the mini-brains grown from people with autism, they found something unusual. The developing forebrain contained too many excitatory neurons.
These are brain cells that send signals to other neurons and help brain regions communicate with each other. In a healthy brain, there is usually a careful balance between excitatory neurons, which increase activity, and inhibitory neurons, which reduce activity. This balance allows the brain to work smoothly.
However, in the mini-brains linked to autism, the researchers saw an overproduction of excitatory neurons. This imbalance may cause brain circuits to become overly active. Scientists believe that this early difference in cell growth could help explain some of the brain changes seen in autism later in life.
The researchers also noticed that this early brain overgrowth may be connected to head size. Some children with autism are known to have larger head sizes during early development. The findings suggest that this may be related to the rapid growth of certain brain cells before birth.
To understand what was happening inside each cell, the scientists used a powerful technique called single-cell RNA sequencing. This method allows researchers to examine individual cells and see which genes are turned on or off. By doing this, they can understand how each cell behaves during development.
The research team studied more than 664,000 individual brain cells at three different stages of early growth. This massive dataset gave them a detailed picture of how genes control the development of the forebrain.
One gene stood out in particular. The gene, called FOXG1, has been linked to brain development for many years. It plays a key role in shaping the forebrain during pregnancy. In the new study, the researchers found that FOXG1 activity was higher in the mini-brains from people with autism. This change may help drive the increased production of excitatory neurons.
The discovery builds on more than a decade of collaboration between Dr. Alexej Abyzov of Mayo Clinic and Dr. Flora Vaccarino of Yale University. Their research focuses on understanding the biological roots of autism by studying how the brain develops before birth.
Dr. Abyzov believes that one day scientists may be able to identify a baby’s risk of autism even before birth through genetic testing during pregnancy. However, he says this will only be possible once researchers fully understand the biological processes that lead to autism. Studies using mini-brain models are helping scientists piece together this complex puzzle.
Although the work is still at an early stage, the findings provide a clearer picture of how autism may begin during the earliest moments of brain development. By studying these tiny brain models, researchers hope to uncover new ways to detect autism earlier and possibly develop better treatments in the future.
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The research was published in the journal Nature Neuroscience.
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