3D -Miniature Human Brains show Irregular Neuron Development in Autistic Patients

FOXG1 is a gene responsible for irregular neuron development in the brain of autistic children.Impact of this gene must be considered for future treatments.

Most children with Autism Spectrum Disorder (ASD) suffer from a condition known as macrocephaly in which the head is larger than normal.

To get a better understanding of the disorder, the signs of risk and for the development of new drugs, researchers at Yale School of Medicine developed “miniature brains” from skin cells of autistic patients.

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The researchers used skin biopsies of four autistic patients to stimulate early cerebral cortex development.

These cells were grown for 31 to 100 days into three-dimensional stimulated miniature human brains (brain organoids).

Further the researchers compared gene expression and developing cell types between the patients and their family members, mainly fathers, without the disorder.

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“We discovered that the patients’ cells divided at a faster pace, and that they produced more inhibitory neurons and more synapses,” said lead author Dr. Flora Vaccarino, professor of neurobiology at Yale School of Medicine.

The researchers explained that the brains of autistic infants have abnormal activities within the cell cycles, mainly those concerned with inhibitory neurons that keep the excitation in check.

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The researchers found that gene FOXG1 was responsible for the irregular neuron development in the brain of an autistic child. They also found a 10-fold increase in FOXG1 in the miniature brains.

“By regulating FOXG1 expression levels in patients’ neural cells, we were able to reverse some of the neurobiological alterations,” Vaccarino said. “Indeed, correcting the FOXG1 over expression prevented the overproduction of inhibitory neurons in patient’s cells. Remarkably, we also found a link between the extent of change in gene expression and the degree of a patient’s macrocephaly and autism severity.”

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Researchers concluded that future treatments for autism should consider the impact of FOXG1 gene.

The study is published in the journal Cell.

Source-Medindia