Scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown that a single protein plays an oversized role in intellectual and behavioral development.
The scientists found that mutations in a single gene, which is known to cause intellectual disability and increase the risk of developing autism spectrum disorder, severely disrupts the organization of developing brain circuits during early childhood.
This study helps explain how genetic mutations can cause profound cognitive and behavioral problems.
The study was published in the Nov. 9, 2012, issue of the journal Cell.
The genetic mutations that cause developmental disorders, such as intellectual disability and autism spectrum disorder, commonly affect synapses, the junctions between two nerve cells that are part of the brain's complex electro-chemical signaling system.
A substantial percentage of children with severe intellectual and behavioral impairments are believed to harbor single mutations in critical neurodevelopmental genes.
Until this study, however, it was unclear precisely how pathogenic genetic mutations and synapse function were related to the failure to develop normal intellect.
"In this study, we did something no one else had done before," said Gavin Rumbaugh, a TSRI associate professor who led the new research.
"Using an animal model, we looked at a mutation known to cause intellectual disability and showed for the first time a causative link between abnormal synapse maturation during brain development and life-long cognitive disruptions commonly seen in adults with a neurodevelopmental disorder."
Losing Balance
The study focused on a critical synaptic protein known as SynGAP1. Mutations in the gene that encodes this protein cause disabilities in an estimated one million people worldwide, according to the paper.
"There are a few genes that can't be altered without affecting normal cognitive abilities," Rumbaugh said. "SynGAP1 is one of the most important genes in cognition -- so far, every time a mutation that disrupts the function of SynGAP1 has been found, that individual's brain simply could not develop correctly.
It regulates the development of synaptic function like no other gene I've seen."
Using animal models that were missing just one copy of SynGAP1, as seen in some patients with intellectual disability, the scientists found that certain synapses develop prematurely in the period shortly after birth.
This dramatically enhances what is known as "excitability" -- how often brain cells fire -- in the developing hippocampus, a part of the brain critical for memory.
The balance between excitability and inhibition is especially critical during early developmental periods, when neural connections that ultimately give rise to normal cognitive and behavioral functions are forming.
"You might think this accelerated development of brain circuits would make you smarter," Rumbaugh said. "But the increased excitability actually disorganizes brain development.
We think that early maturation of these excitatory synapses disrupts the timing of later developmental milestones.
It rains down chaos on this complex process, preventing normal intellectual and behavioral development."
Read the full article here
The scientists found that mutations in a single gene, which is known to cause intellectual disability and increase the risk of developing autism spectrum disorder, severely disrupts the organization of developing brain circuits during early childhood.
This study helps explain how genetic mutations can cause profound cognitive and behavioral problems.
The study was published in the Nov. 9, 2012, issue of the journal Cell.
The genetic mutations that cause developmental disorders, such as intellectual disability and autism spectrum disorder, commonly affect synapses, the junctions between two nerve cells that are part of the brain's complex electro-chemical signaling system.
A substantial percentage of children with severe intellectual and behavioral impairments are believed to harbor single mutations in critical neurodevelopmental genes.
Until this study, however, it was unclear precisely how pathogenic genetic mutations and synapse function were related to the failure to develop normal intellect.
"In this study, we did something no one else had done before," said Gavin Rumbaugh, a TSRI associate professor who led the new research.
"Using an animal model, we looked at a mutation known to cause intellectual disability and showed for the first time a causative link between abnormal synapse maturation during brain development and life-long cognitive disruptions commonly seen in adults with a neurodevelopmental disorder."
Losing Balance
The study focused on a critical synaptic protein known as SynGAP1. Mutations in the gene that encodes this protein cause disabilities in an estimated one million people worldwide, according to the paper.
"There are a few genes that can't be altered without affecting normal cognitive abilities," Rumbaugh said. "SynGAP1 is one of the most important genes in cognition -- so far, every time a mutation that disrupts the function of SynGAP1 has been found, that individual's brain simply could not develop correctly.
It regulates the development of synaptic function like no other gene I've seen."
Using animal models that were missing just one copy of SynGAP1, as seen in some patients with intellectual disability, the scientists found that certain synapses develop prematurely in the period shortly after birth.
This dramatically enhances what is known as "excitability" -- how often brain cells fire -- in the developing hippocampus, a part of the brain critical for memory.
The balance between excitability and inhibition is especially critical during early developmental periods, when neural connections that ultimately give rise to normal cognitive and behavioral functions are forming.
"You might think this accelerated development of brain circuits would make you smarter," Rumbaugh said. "But the increased excitability actually disorganizes brain development.
We think that early maturation of these excitatory synapses disrupts the timing of later developmental milestones.
It rains down chaos on this complex process, preventing normal intellectual and behavioral development."
Read the full article here
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