Gene In Down Syndrome Patients Stops Other Neurons’ Action

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 University of Michigan (U-M) presented this as 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. Their findings are published in the journal PLOS Biology.

Researchers Target an Aspect of Down Syndrome

In this study, researchers 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. They previously determined that an overabundance of the protein encoded by DSCAM can cause an overgrowth of axons in fruit fly neurons.

Now, they have found that a third copy of DSCAM in mice leads to increased axon (part of the 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 behavior. They also showed that the extra copy of DSCAM is the primary cause of the excessive inhibitory synapses in the cerebral cortex.

The normal axon growth in mice was present with 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.

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

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The modulation of DSCAM expression levels could be a viable therapeutic strategy for repairing synaptic deficits seen in Down syndrome. In addition, given that alterations of DSCAM levels are associated with other brain disorders like autism spectrum disorder and bipolar disorder, these results shed insight into potential mechanisms underlying other human diseases.

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Source-Eurekalert