JOIN USResearchers have discovered that the extra chromosome inherited in Down’s syndrome impairs learning and memory because it leads to low levels of a brain protein.
Scientists at Sanford-Burnham Medical Research Institute have new evidence that points to a protein called sorting nexin 27, or SNX27.
SNX27 production is inhibited by a molecule encoded on chromosome 21. The study, published in Nature Medicine, shows that SNX27 is reduced in human Down’s syndrome brains.
The extra copy of chromosome 21 means a person with Down’s syndrome produces less SNX27 protein, which in turn disrupts brain function.
The researchers showed that restoring SNX27 in Down’s syndrome mice improves cognitive function and behaviour.
“In the brain, SNX27 keeps certain receptors on the cell surface - receptors that are necessary for neurons to fire properly,” said Huaxi Xu, senior author of the study. “So, in Down syndrome, we believe lack of SNX27 is at least partly to blame for developmental and cognitive defects,” Xu said in a statement.
Xu and colleagues started out working with mice that lack one copy of the snx27 gene. They noticed that the mice were mostly normal, but showed some significant defects in learning and memory.
They found that SNX27 helps keep glutamate receptors on the cell surface in neurons. Neurons need glutamate receptors in order to function correctly. With less SNX27, these mice had fewer active glutamate receptors and thus impaired learning and memory.
The SNX27-deficient mice shared some characteristics with Down’s syndrome, so they took a look at human brains with the condition. This confirmed the clinical significance of their laboratory findings - humans with Down’s syndrome have significantly lower levels of SNX27.
Xu and colleagues suspected microRNAs, small pieces of genetic material that don’t code for protein, but instead influence the production of other genes.It turns out that chromosome 21 encodes one particular microRNA called miR-155.
In human Down’s syndrome brains, the increase in miR-155 levels correlates almost perfectly with the decrease in SNX27. Xu and his team concluded that, due to the extra chromosome 21 copy, the brains of people with Down’s syndrome produce extra miR-155, which by indirect means decreases SNX27 levels, in turn decreasing surface glutamate receptors.