Analysis: the study of fused brain cells in worms may contribute to our understanding of many human brain diseases and disorders

One of the most exciting parts of science is discovering exceptions to different biological rules. Barbara McClintock discovered that genetic information isn't static in some organisms. Intriguingly, portions of genes encoded machinery that allowed them to jump around the genome. This discovery lead to gradual advances in our understanding of genetics, building a foundation for future genetic research.

In neuroscience, it was thought that neuronal cells were distinct. However, recent discoveries found fused cells in the brains of certain animal models of disease. Now, scientists at the University of Queensland found that these fused nerve cells impact basic behaviours in worms. 

Many cells within our body are fused together, serving a synchronized function. As an example, the cells in our heart are connected to each other so that they can quickly communicate signals regulating cardiac function. But when it comes to the brain, we haven’t found any such fusions of nerve cells in healthy individuals. The protein Syncytin-1  is found expressed in brain cells of individuals with multiple sclerosis. This protein is usually present in other tissues where fused cells are the norm.

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From University of Queensland, Massimo Hilliard on how a small worm could pave the way for new discoveries in neuroscience

According to one of the authors of the new report Massimo Hilliard, "we have limited knowledge of the effect of fusogens in neurons, and what happens if neurons fuse together, so we explored these questions in the one millimeter-long nematode worm C. elegans, where we can easily visualize neurons under the microscope and manipulate their genes."

Caenorhabditis elegans (C. elegans) is a powerful tool for studying developmental biology, neuroscience and pharmacology. These worms only possess 302 neuronal cells so researchers could see the overall impact of fusing two of these nerve cells. While each cell is responsible for delivering specific messages, their wires cross together when fused. This means that if the worm needed to use one of these cells, it would also activate the cell it is fused to. The authors likened this to a light-switch turning on lightbulbs in two different rooms.

Researchers fused specific pairs of nerve cells to see how this impacted the behaviour of C. elegans. Some of these neurons help the worms find food by attracting them to delicious odors. Similarly, unpleasant odors activate specific neurons that repel the worms. When two nerve cells responsible for attracting worms towards an odor were fused, their functions were not changed. However, when one of these nerve cells attracted the worm to food while the other repelled it, the worms had difficulty navigating towards food. These effects also impacted the worms' ability to navigate away from danger.

Could these cell fusions exacerbate some of the symptoms and dysfunctions associated with brain diseases and disorders?

When the fused neurons are already involved in the same circuit, the authors did not detect any problems in the worms. However, only when a different nerve cell involved in a different circuit fused the worms’ ability to find their food. Much like our own, the worm's brain cells propagate messages through electrical signals. Usually, once the electrical signal reached the end of a brain cell, it would release a chemical signal to activate the next cell in its circuit. But when two cells are connected, the signal simultaneously travels to both. When two different circuits are crossed, the electrical signal is compromised.

Interestingly, the protein involved in nerve cell fusion in humans, Syncytin-1, evolved from viral genes and incorporated itself into our genome. There are plenty of other elements in our genetic code that also evolved from viral genes. It’s unclear if some of these elements may also lead to cells fusing.

Viruses such as the Herpes Simplex Virus attack human brain cells and it's possible that they may insert portions of themselves into individual brain cells, thus leading to fusion. This virus is also found in the brains of individuals with Alzheimer's Disease. Could these cell fusions exacerbate some of the symptoms and dysfunctions associated with brain diseases and disorders? Or are cell fusions characteristic of disease mechanisms themselves?

READ: Do worms hold the answer to our food cravings?

At this stage, these are questions for further studies to answer. While the study of these fused brain cells is still in its infancy, it may underlie new mechanisms that contribute to many brain diseases and disorders. In fact, few new treatments for neuropsychiatric and neurodegenerative diseases have been found effective in recent years. Perhaps understanding how fused cells disrupt brain circuitry and signalling could point us towards new therapeutics?


The views expressed here are those of the author and do not represent or reflect the views of RTÉ