Mutations in two genes that regulate a
neurotransmitter essential for forebrain development can lead to brain
David Eisenstat and his team examined a neurotransmitter in the brain called
GABA which is essential to forebrain development in the embryo. They found that
two specific genes, DLX1 and DLX2, regulate GABA synthesis during brain
development, and that mutations to the genes resulted in abnormal brain
‘Mutations in the DLX1 and DLX2 gene during embryo development can cause autism, seizure disorder in children and behavioral issues in adults.’
If these mutations happen during embryonic development, there could be
several neurological problems: the child could become autistic, kids could be
born with seizure disorder, or the developing neurons might not migrate to
their proper site in the brain. In adults, there could be behavioural issues.
"Our findings have potential implications for autism and seizure
disorders that currently aren't treatable--at least not by targeting
GABA," said Eisenstat, the senior author of the study and chair of the
Department of Oncology at the U of A as well as professor in the departments of
Pediatrics and Medical Genetics.
According to the researcher, GABA is the most important inhibitory
neurotransmitter in the brain. It is produced when DLX1 and DLX2 genes act as a
molecular switch, activating an enzyme that converts a chemical called
glutamate to GABA. Problems occur when the balance between glutamate--an
excitatory neurotransmitter in the brain and nervous system--and GABA fall out
"GABA tells the brain to slow down. Glutamate tells the brain to speed
up. A healthy brain is found in the balance," explained Eisenstat.
"In some ways we have figured out how to turn on GABA. And if, going back
to these diseases, we have a better idea of how to balance glutamate and GABA,
we could potentially come up with new therapies for treating seizures and maybe
even some children with autism."
He said that while that may sound like a lot of hand waving, 25 percent of
children with autism have a seizure disorder.
"That's not well understood. It's not all because of GABA, that would
be an oversimplification, but this hypothesis is worth further testing,"
Eisenstat believes the findings have revealed a new pathway scientists could
use to treat developmental brain disorders by getting to the root cause of
problem. He hopes other researchers now take up the work and build upon it.
"I think we've unraveled a pathway to begin to take something that
wasn't druggable and make it druggable," said Eisenstat. "I think in
some ways, it's coming up with smarter therapy."