May 29, 2018
Children who experience seizures at a crucial point in the development of their brains could face a higher risk of intellectual disability and autism, according to new research from the University of Pennsylvania.
The relationship between epileptic seizures and autism has become an area of growing focus as diagnoses continue to trend upwards in the United States.
About one in 60 U.S. children have autism, according to the Centers for Disease Control and Prevention, and as many as 40 percent of those with autism or intellectual disability also suffer from epilepsy. About 35 percent of children with infantile spasms go onto have long-term developmental disabilities.
A new study from Penn Medicine, published online in Cell Reports, notes that early-life seizures often activate synapses that may contribute to neurodevelopment delays in children.
The researchers found that when seizures were induced in mice, “silent” thalamocortical synapses in the auditory cortex were jolted into an active state. These pathways serve as the primary route of sensory information to the cerebral cortex.
Without the seizures, these thalamocortical synapses contained only NMDA receptors. With them, they contained both NMDA and AMPA receptors, both of which play important roles in learning and memory formation. The Penn researchers believe premature activation of AMPA receptors contributed to critical neurodevelopment delays.
“Understanding the precise synaptic changes following seizures gives an opportunity to find treatments that can prevent this early ‘unsilencing,’” said senior author Frances E. Jensen, chair of the department of neurology at the Perelman School of Medicine. “The timing is important: We need to stop it right after the seizures and before a critical period of development in a child’s life so the brain can develop without any problems that may lead to future impairments.”
To test a potential treatment, the researchers induced seizures in mice and provided them with an AMPA receptor antagonist, an antiepileptic and anticonvulsant drug. They determined that this approach reduced premature AMPA receptor activation and restored synaptic plasticity during the critical period.
“This is proof of principle that synaptic plasticity is a dynamic target for the treatment of autism and intellectual disabilities that accompany early-life seizures,” Jensen said. “Further exploration will not only gain more insight into the etiology and treatment of autism, but also other neurodevelopmental disorders.”