Scientists find that restoring pleiotrophin in the brain could improve brain function in Down syndrome, offering a promising new approach for treating neurological disorders.
Faulty brain circuits seen in Down syndrome may be a result of the absence of a critical molecule, new research finds. This discovery could pave the way to significant advancements in treatment for Down syndrome and other neurological disorders.
Published in the journal Cell Reports, the study revealed that the molecule, known as pleiotrophin, is crucial for the development and function of the nervous system. The researchers found that restoring pleiotrophin in the brains of adult lab mice significantly improved brain function, suggesting potential for similar treatments in humans.
“This study is really exciting because it serves as proof-of-concept that we can target astrocytes, a cell type in the brain specialized for secreting synapse-modulating molecules, to rewire the brain circuitry at adult ages,” first author Ashley N. Brandebura, who conducted the study as a postdoctoral student at Salk Institute for Biological Studies and is now an assistant professor of neuroscience at the University of Virginia School of Medicine, said in a news release. “This is still far off from use in humans, but it gives us hope that secreted molecules can be delivered with effective gene therapies or potentially protein infusions to improve quality of life in Down syndrome.”
Down syndrome, which affects about 1 in 640 babies born annually in the United States according to the Centers for Disease Control and Prevention, is caused by errors in cell division. These errors can result in developmental delays, hyperactivity and increased risks for various medical issues, such as heart defects and thyroid problems.
Salk Institute researchers, led by Nicola J. Allen, aimed to understand the underlying causes of Down syndrome better. They discovered pleiotrophin as a promising candidate by examining cellular proteins altered in the brains of lab mice modeling the condition. This protein is present at high levels during critical moments in brain development, playing a vital role in forming synapses and developing nerve transmitters.
To test if replenishing pleiotrophin could improve brain function, the researchers used modified viruses to deliver the molecule to the brain cells where it was needed. These engineered viruses, known as viral vectors, insert beneficial cargo into cells without causing disease.
The results were promising: pleiotrophin administration in pivotal brain cells, specifically astrocytes, increased the number of synapses in the hippocampus, enhancing brain plasticity and potentially restoring cognitive functions.
“These results suggest we can use astrocytes as vectors to deliver plasticity-inducing molecules to the brain,” Allen said in the news release. “This could one day allow us to rewire faulty connections and improve brain performance.”
While these findings are hopeful, the researchers caution that pleiotrophin is likely not the only factor contributing to brain circuit issues in Down syndrome. More comprehensive research is necessary to fully understand the condition’s complexities.
The successful use of astrocytes to deliver synaptogenic molecules could also have broader applications, potentially benefiting treatments for various neurological disorders.
“This idea that astrocytes can deliver molecules to induce brain plasticity has implications for many neurological disorders, including other neurodevelopmental disorders like fragile X syndrome but also maybe even to neurodegenerative disorders like Alzheimer’s disease,” Brandebura added. “If we can figure out how to ‘reprogram’ disordered astrocytes to deliver synaptogenic molecules, we can have some greatly beneficial impact on many different disease states.”