Il Hwan Kim, PhD, a researcher at the University of Tennessee Health Science Center, has witnessed firsthand the challenges and heartaches faced by parents raising children with autism spectrum disorder (ASD) in the United States.
“It’s always so moving when I hear their stories,” said Dr. Kim, an associate professor of anatomy and neurobiology in the College of Medicine. “One friend, whose child has ASD, once confided that her greatest wish is to hear her child call her ‘mom’ out loud someday. It’s truly heart-wrenching.”
Driven by these personal connections, Dr. Kim’s latest study is a testament to his commitment to understanding ASD and finding ways to alleviate the burdens it places on families.
Little is understood about the mechanisms underlying ASD, especially given its prevalence, affecting approximately one in every 36 children. ASD is a complex neurodevelopmental disorder that influences how individuals perceive the world and interact with others. While the exact causes of autism remain largely unknown, scientists have long suspected that both genetic and environmental factors play significant roles.
Dr. Kim is leading a team of researchers whose discoveries have unveiled a crucial mechanism of the blood-brain barrier (BBB) in ASD development. “The blood-brain barrier is often considered the brain’s gatekeeper,” Dr. Kim explained. “This barrier is like a highly selective security checkpoint, deciding what substances get access to our brain.”
At the heart of their research is a gene called SHANK3, known for its involvement in brain development and function. Mutations in SHANK3 have been linked to ASD, but until now, its role in the BBB was uncharted territory. The research team, which includes postdocs Yong-Eun Kim, PhD, and Sunwhi Kim, PhD, and PhD candidate Yusuke Ujihara, embarked on a mission to explore whether SHANK3 could influence the integrity of the BBB and, in turn, contribute to ASD.
Their findings were groundbreaking. The study revealed that SHANK3 is expressed in the endothelial cells of the BBB, the very cells responsible for forming the barrier itself. “When SHANK3 was selectively knocked out in these cells in neonatal mice, our team observed a curious phenomenon: the male mice showed increased permeability of the BBB, meaning the barrier was more ‘leaky’ than usual,” Dr. Kim said. “This led to reduced neuronal excitability and impaired communication behaviors, which are hallmark features of ASD.”
The team found an interesting twist: although the BBB’s permeability normalized as the mice matured, the neuronal and social impairments persisted into adulthood. “This suggests that early disruptions in the BBB could have lasting effects on brain function, underscoring a critical window during brain development that could be targeted for therapeutic interventions,” Dr. Kim said.
The team also identified a potential mechanism involving a protein called β-Catenin, which is crucial for maintaining the tight junctions in the BBB. By modulating β-Catenin signaling in the affected mice, the researchers were able to restore the BBB’s function and significantly improve the mice’s neuronal activity and social behaviors.
The project findings, which have been published in Nature Communications, opens a promising new avenue for treatment. By understanding the role of the BBB in ASD, scientists can now explore therapies that target this barrier during critical developmental stages. The prospect of intervening early to prevent or mitigate the onset of ASD symptoms is an exciting development that could transform lives.
While this research is still in its early stages and primarily conducted in mice, the implications are profound. It highlights the importance of the BBB in brain health and its potential as a therapeutic target for neurological disorders. As scientists continue to unravel the mysteries of the brain, this discovery brings us one step closer to understanding and ultimately improving the lives of those affected by autism.