Gene in Down syndrome patients found to inhibit other neurons’ activities

The gene is called Down syndrome cell adhesion molecule, or DSCAM

Researchers have found that an extra copy of a gene in Down syndrome patients, also implicated in other human neurological conditions such as autism spectrum disorders, bipolar disorder and intractable epilepsy, causes improper development of neurons in mice.

The gene is called Down syndrome cell adhesion molecule, or DSCAM.

An extra copy of chromosome 21, or trisomy 21, is known to be the cause of Down syndrome, but it contains more than 200 genes, including DSCAM.

The researchers from University of Michigan (U-M), US, said that this presented a major challenge in Down syndrome research and treatments, which is determining which gene(s) on the chromosome contribute to which specific symptoms of the syndrome.

“For Down syndrome, we can’t just sequence patient genomes to find such genes, because we’d find at least 200 different genes that are changed. We have to dig deeper to figure out which of those genes causes which problem,” said Bing Ye, a neuroscientist at the U-M Life Sciences Institute and lead author of the study.

Their findings are published in the journal PLOS Biology.

In this study, Ye and his team have demonstrated how an extra copy of DSCAM contributes to neuronal dysfunction by studying mice having a third copy of the mouse equivalent of chromosome 21.

Ye and colleagues previously determined that overabundance of the protein encoded by DSCAM can cause overgrowth of axons in fruit fly neurons.

Now, the team has found that a third copy of DSCAM in mice leads to increased axon (part of neuron that sends signals to other neurons) growth and neuronal connections, called synapses, in the types of neurons that put the brakes on other neurons’ activities.

These changes lead to greater inhibition of other neurons in the cerebral cortex - a part of the brain that is involved in sensation, cognition and behaviour.

“We show here that the extra copy of DSCAM is the primary cause of the excessive inhibitory synapses in the cerebral cortex,” said Ye.

The team demonstrated normal axon growth in in mice having only two copies of DSCAM, but three copies of the other genes that are similar to human chromosome 21 genes.

“These results are striking because, although these mice have an extra copy of about a hundred genes, normalization of this single gene, DSCAM, rescues normal inhibitory synaptic function,” said Paul Jenkins, assistant professor of pharmacology and psychiatry at the Medical School and co-corresponding author of the study.

“This suggests that modulation of DSCAM expression levels could be a viable therapeutic strategy for repairing synaptic deficits seen in Down syndrome,” said Jenkins.

https://www.tribuneindia.com/news/health/gene-in-down-syndrome-patients-found-to-inhibit-other-neurons-activities-499608