A new research identifies a genetic abnormality that is linked to the development of health problems seen in patients with Down syndrome.
Down syndrome is one of the most common genetic disorders in the world. The disorder is characterized by the presence of a third copy of chromosome 21, which is the smallest chromosome in the human body.
Previous studies mostly focused on the role of the central nervous system (CNS), which is responsible for intellectual abilities. Such trend leaves the role of the peripheral nervous system hardly tapped, amid affected patients exhibiting associated clinical manifestations.
The peripheral nervous system has no role in intellectual ability, but it does facilitate several organ functions such as blood pressure, heart rate and blood glucose.
Corresponding author Rejji Kuruvilla said the fact that scientists only study the CNS when investigating Down syndrome overlooks a lot of details.
"There's been a whole aspect of the nervous system that has been ignored in Down syndrome, and perhaps in other neurological disorders" he said.
The connection between Down syndrome and the peripheral nervous system has been recognized in the past, but cellular and molecular investigations are lacking. The researchers of the new study then conducted an experiment involving human tissues of Down syndrome infants and mice engineered to have the disorder.
The researchers found that the pancreatic and spleen tissues in both samples have very little peripheral nerve growth in the early stages of life.
With this, the authors focused on nerve growth factor (NGF), which regulates nervous system development.
They then discovered that a gene called RCAN1 is the main reason why NGF's actions are hampered. The amount of the said gene is three times more in individuals with Down syndrome. The right amount of RCAN1 facilitates a protein called calcineurin, which empowers NGF to perform its supportive and stimulative functions for neuron survival and nerve growth respectively.
When the scientists tripled RCAN1 in a mouse model, neurons and nerve growth were lost. Removing the excessive gene, therefore, improved neuronal survival and nerve growth.
Such finding signifies that adding more RCAN1 does not enhance function, and inadequate calcineurin activity negatively impacts the peripheral nervous system.
"These results uncover a critical link between calcineurin signalling, impaired neurotrophin trafficking and neurodevelopmental deficits in the peripheral nervous system in Down syndrome," the authors wrote.
In the future, the researchers want to investigate how RCAN1 influences neurons located in the basal forebrain, which also reacts to NGF and deteriorates in patients with Alzheimer's disease.
In the end, Kuruvilla said it is important to pay attention to the vital peripheral nervous system when thinking about life quality-changing therapeutic measures.
The study was published in the journal Nature Communications on Monday, Dec. 14.
Photo : William Murphy | Flickr
