Major discovery in the genetics of Down syndrome

February 21, 2020

Researchers at CHU Sainte-Justine and Université de Montréal have discovered a new mechanism involved in the expression of Down syndrome, one of the main causes of intellectual disability and congenital heart defects in children. The study's findings were published today in Current Biology.

Down syndrome (SD), also called trisomy 21 syndrome, is a genetic condition that affects approximately one in every 800 children born in Canada. In these individuals, many genes are expressed abnormally at the same time, making it difficult to determine which genes contribute to which differences.

Professor Jannic Boehm's research team focused on RCAN1, a gene that is overexpressed in the brains of fetuses with Down syndrome. The team's work provides insights into how the gene influences the way the condition manifests itself.

Synaptic plasticity, memory and learning

The human brain is made up of hundreds of billions of cells known as neurons. They communicate with each other through synapses, which are small gaps between neurons. The ability of synapses to strengthen or weaken over time is known as "synaptic plasticity." It's an important biological phenomenon because it's essential for memory and learning.

"There are two kinds of synaptic plasticity: long-term potentiation, which strengthens synapses and improves interaction between neurons, and long-term depression, which weakens synapses," said Boehm, a professor at Université de Montréal and researcher at CHU Sainte-Justine.

"We already knew that synaptic plasticity is influenced by certain proteins," added Anthony Dudilot, one of the study's first authors. "For example, calcineurin is inhibited when long-term potentiation is induced, but it's activated when long-term depression begins. But the molecular mechanism underlying calcineurin regulation was less clear."

The research team found that the various signalling pathways that trigger synaptic potentiation or depression converge on RCAN1. They also determined that the gene regulates calcineurin activity by inhibiting or facilitating it.

Given its dual role as an inhibitor/facilitator, the researchers deduced that RCAN1 works as a "switch" that regulates synaptic plasticity, thereby affecting learning and memory.

A better future for all patients

"This is the first time that the molecular mechanism for calcineurin regulation in bidirectional synaptic plasticity has been determined," said Boehm. "This breakthrough explains how overexpression of the RCAN1 gene could cause intellectual disabilities in individuals with Down syndrome. It also opens up the possibility of developing innovative treatments for affected patients."
-end-
About the study

"RCAN1 regulates bidirectional synaptic plasticity" was published in Current Biology in February 2020. The first authors are Anthony Dudilot and Emilie Trillaud-Doppia, PhD candidates supervised by Jannic Boehm. The senior author is Jannic Boehm, PhD, an associate professor at UdeM's Department of Neurosciences and researcher at CHU Sainte-Justine. The study was backed by the Canadian Institutes of Health Research (CIHR), Fonds de recherche du Québec - Santé (FRQS), the Alzheimer Society of Canada and Université de Montréal.

About the CHU Sainte-Justine Research Centre

CHU Sainte-Justine Research Centre is a leading mother-child research institution affiliated with Université de Montréal. It brings together more than 200 research investigators, including over 90 clinicians, as well as 350 graduate and post-graduate students focused on finding innovative means of prevention, faster and less invasive treatments, and personalized approaches to medicine. The Centre is part of CHU Sainte-Justine, which is the largest mother-child hospital in Canada and second most important pediatric hospital in North America.

University of Montreal

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.