• Alex Savin
• March 18, 2022
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The possibility to breathe easier

We see amazing scientific breakthroughs every day, and these help us understand our bodies better and learn to treat them better. As per the latest news from the Langone Medical Center at NYU, the scientists have found two genes that create the neuronal circuits essential for breathing. This new information could be very helpful when advancing treatments in neurodegenerative diseases like ALS, which is responsible for killing neurons that control muscle movement required for eating, breathing, and even moving. The find will also help advance treatments in spinal cord injuries.

Scientific Explanation of Breathing

The study has found code in the molecules that identify a phrenic motor column (PMC), a group of nerve cells that control the muscles. These are present in our body almost halfway up in the back of our neck, above our fourth cervical vertebra, and are considered very important motorneurons in the body. That is clear by their function; if these neurons malfunction, we could face troubles performing basic tasks. In some cases, even breathing could become difficult. Jeremy Dasen, a member of Howard Hughes Institute and an assistant professor of psychology and neuroscience, indicates that the normal functioning of these neurons is very important for us to function normally and independently. Jeremy Dasen has also led a three-year-long study with Dr. Polyxeni Philippidou.

The find indicates that if these neurons are harmed, a lot of damage can happen to the body instantly, and any harm to the spinal cord that has these neurons can immediately shut down breathing. That is how important this discovery is. If the PMC neurons degenerate, they could lead to death in patients who have ALS or spinal cord injuries.

The scientists have still not identified how these PMC neurons can be identified from the others present in the body and how these neurons can develop themselves in the fetus’s diaphragm. However, we know that these PMC neurons ensure a regular flow of electrochemical signals through their axons that are bundled and to the diaphragm muscles. This process makes it possible for the lungs to relax and expand to make natural breathing possible. Dr. Dasen states that they have found a set of markers for the neurons that can identify the cells from all the other neurons. It has become easy to study them with a lot of focus and find newer ways to make the chances of their survival better and healthier selectively.

To further understand how the PMC neurons can be distinguished from the other spinal cord neurons, Dr. Philippidou started by injecting a fluorescent tracer in the phrenic nerve in transgenic mice. This nerve connects the PMC neurons to the diaphragm, and after injecting the tracer, Dr. Philippidou looked for all the neurons in the spine that light up while the tracer traveled towards the PMC. Using transgenic mice is that they express the green fluorescent protein (GFP) in their neurons and axons. This made it possible for the scientists to view the phrenic nerve. After the pattern of expression of the genes was identified, Dr. Philippidou started identifying the specific roles they play. After much research, he came across a complex strain of these transgenic mice. Also, he considered the results received from the mice provided through another collaborator Lucie Jeannotte, at the University of Quebec. Two genes, called Hoxa5 and Hoxc5, came out as the major controllers in the proper development of PMC. It is important to know here that the Hox genes are responsible for gene regulation in animal development, and in humans, there are 39 of them expressed. In mice, it was noticed that when these two genes are silenced, the PMC becomes unable to form their highly complex and tight columnar organization and is unable to connect with the diaphragm…this leads to the newborn not being able to breathe at all.

Learning to Breathe Again

Dr. Dasen says that if these genes are deleted in late fetal development, the PMC neuron numbers drop, and the nerve under discussion cannot form enough to create enough branches to reach the diaphragm muscles. As per Dr. Dasen, the plan is to utilize the findings to understand the entire breathing process better. This would include the neurons that generate rhythm in the brain stem that respond to carbon dioxide levels, understand stress, and other environmental factors. He also says that now they know more about the PMC cells and are better equipped to understand how breathing works and how all the connections form. Both the scientists are hopeful that once a deeper understanding of the respiratory network and its formation is created, better ways to treat breathing disorders can be created and used.

Even though Dr. Dasen lost most of his research to Hurricane Sandy while the study was still on and in its final stages, he had shipped some of them to Quebec. That helped reach the final stages and complete the research that will in the future benefit a very big population.