Zebrafish give new insight to sound sensitivity in autism

These tiny fish are helping scientists understand how the human brain processes sound.

zebrafish
Credit: peter verreussel / Adobe Stock
  • Fragile X syndrome is a genetic disorder caused by changes in a gene that scientists call the "fragile X mental retardation 1 (FMR1)" gene. People who have FXS or autism often struggle with sensitivity to sound.
  • According to the research team, FXS is caused by the disruption of a gene. By disrupting that same gene in zebrafish larvae, they can examine the effects and begin to understand more about this disrupted gene in the human brain.
  • Using the zebrafish, Dr. Constantin and the team were able to gather insights into which parts of the brain are used to process sensory information.

Associate professor Ethan Scott and Dr. Lena Constantin recently carried out a study using zebrafish that carry the same genetic mutations as humans with "Fragile X" syndrome and autism. During their research, they discovered the neural networks and pathways that produce hypersensitivities to sound in both zebrafish and humans.

What is Fragile X syndrome?

Fragile X syndrome (commonly referred to as FXS) is a genetic disorder caused by changes in a gene that scientists call the "fragile X mental retardation 1 (FMR1)" gene. This gene typically makes a protein called fragile X mental retardation protein (FMRP) that's needed for typical brain development. The brains of people with FXS do not make this protein, and if it is there, it's abnormal.

What is autism?

Autism spectrum disorder (ASD) is a developmental disability that can cause significant social, communication, and behavioral challenges. People with ASD may communicate, interact, behave, and learn in different ways than most other people. A current diagnosis of ASD now includes several conditions that were previously diagnosed separately such as autistic disorder, pervasive developmental disorder, and Asperger syndrome.

zebrafish swimming in a tank

By disrupting a specific gene in Zebrafish, we're able to better understand the same disruption of that gene in humans with FXS or autism.

Credit: slowmotiongli on Adobe Stock

"Loud noises often cause sensory overload and anxiety in people with autism and Fragile X syndrome -- sensitivity to sound is common to both conditions," Dr. Constantin explained to Science Daily.

How do zebrafish relate to humans with autism?

According to the research team, FXS is caused by the disruption of a gene. By disrupting that same gene in zebrafish larvae, they can examine the effects and begin to understand more about this disrupted gene in the human brain.

The thalamus, according to Dr. Constantin, works as a control center, relaying sensory information from around the body to different parts of the brain. The hindbrain then coordinates different behavioral responses. Using the different sound tests, the team was able to study the whole brain of the zebrafish larvae under microscopes and see the activity of each brain cell individually.

According to Dr. Constantin, the research team recorded the brain activity of zebrafish larvae while showing them movies or exposing them to bursts of sound. The movies stimulated movement, a reaction to the visual stimuli that was the same for fish with the Fragile X mutation and those without. However, when the fish were given a burst of white noise, there was a dramatic difference in the brain activity of the fish with the Fragile X mutation.

After seeing how the noise radically affected the fish brain, the team designed a range of 12 different volumes of sound and found the Fragile X model fish could hear much quieter volumes than the control fish.

"The fish with Fragile X mutations had more connections between different regions of their brain and their responses to the sounds were more plentiful in the hindbrain and thalamus," said Dr. Constantin.

Essentially, the fish with Fragile X mutation had more connections between the regions of their brain and so their responses to the sounds were more notable.

Understanding how this gene disruption works in zebrafish will give us a better understanding of sound hypersensitivity in humans with FXS or autism.

"How our neural pathways develop and respond to the stimulation of our senses gives us insights into which parts of the brain are used and how sensory information is processed," Dr. Constantin said.

Using the zebrafish, Dr. Constantin and the team were able to gather insights into which parts of the brain are used to process sensory information.

"We hope that by discovering fundamental information about how the brain processes sound, we will gain further insights into the sensory challenges faced by people with Fragile X syndrome and autism."

U.S. Navy controls inventions that claim to change "fabric of reality"

Inventions with revolutionary potential made by a mysterious aerospace engineer for the U.S. Navy come to light.

U.S. Navy ships

Credit: Getty Images
Surprising Science
  • U.S. Navy holds patents for enigmatic inventions by aerospace engineer Dr. Salvatore Pais.
  • Pais came up with technology that can "engineer" reality, devising an ultrafast craft, a fusion reactor, and more.
  • While mostly theoretical at this point, the inventions could transform energy, space, and military sectors.
Keep reading Show less

Why so gassy? Mysterious methane detected on Saturn’s moon

Scientists do not know what is causing the overabundance of the gas.

An impression of NASA's Cassini spacecraft flying through a water plume on the surface of Saturn's moon Enceladus.

Credit: NASA
Surprising Science
  • A new study looked to understand the source of methane on Saturn's moon Enceladus.
  • The scientists used computer models with data from the Cassini spacecraft.
  • The explanation could lie in alien organisms or non-biological processes.
Keep reading Show less

CRISPR therapy cures first genetic disorder inside the body

It marks a breakthrough in using gene editing to treat diseases.

Credit: National Cancer Institute via Unsplash
Technology & Innovation

This article was originally published by our sister site, Freethink.

For the first time, researchers appear to have effectively treated a genetic disorder by directly injecting a CRISPR therapy into patients' bloodstreams — overcoming one of the biggest hurdles to curing diseases with the gene editing technology.

The therapy appears to be astonishingly effective, editing nearly every cell in the liver to stop a disease-causing mutation.

The challenge: CRISPR gives us the ability to correct genetic mutations, and given that such mutations are responsible for more than 6,000 human diseases, the tech has the potential to dramatically improve human health.

One way to use CRISPR to treat diseases is to remove affected cells from a patient, edit out the mutation in the lab, and place the cells back in the body to replicate — that's how one team functionally cured people with the blood disorder sickle cell anemia, editing and then infusing bone marrow cells.

Bone marrow is a special case, though, and many mutations cause disease in organs that are harder to fix.

Another option is to insert the CRISPR system itself into the body so that it can make edits directly in the affected organs (that's only been attempted once, in an ongoing study in which people had a CRISPR therapy injected into their eyes to treat a rare vision disorder).

Injecting a CRISPR therapy right into the bloodstream has been a problem, though, because the therapy has to find the right cells to edit. An inherited mutation will be in the DNA of every cell of your body, but if it only causes disease in the liver, you don't want your therapy being used up in the pancreas or kidneys.

A new CRISPR therapy: Now, researchers from Intellia Therapeutics and Regeneron Pharmaceuticals have demonstrated for the first time that a CRISPR therapy delivered into the bloodstream can travel to desired tissues to make edits.

We can overcome one of the biggest challenges with applying CRISPR clinically.

—JENNIFER DOUDNA

"This is a major milestone for patients," Jennifer Doudna, co-developer of CRISPR, who wasn't involved in the trial, told NPR.

"While these are early data, they show us that we can overcome one of the biggest challenges with applying CRISPR clinically so far, which is being able to deliver it systemically and get it to the right place," she continued.

What they did: During a phase 1 clinical trial, Intellia researchers injected a CRISPR therapy dubbed NTLA-2001 into the bloodstreams of six people with a rare, potentially fatal genetic disorder called transthyretin amyloidosis.

The livers of people with transthyretin amyloidosis produce a destructive protein, and the CRISPR therapy was designed to target the gene that makes the protein and halt its production. After just one injection of NTLA-2001, the three patients given a higher dose saw their levels of the protein drop by 80% to 96%.

A better option: The CRISPR therapy produced only mild adverse effects and did lower the protein levels, but we don't know yet if the effect will be permanent. It'll also be a few months before we know if the therapy can alleviate the symptoms of transthyretin amyloidosis.

This is a wonderful day for the future of gene-editing as a medicine.

—FYODOR URNOV

If everything goes as hoped, though, NTLA-2001 could one day offer a better treatment option for transthyretin amyloidosis than a currently approved medication, patisiran, which only reduces toxic protein levels by 81% and must be injected regularly.

Looking ahead: Even more exciting than NTLA-2001's potential impact on transthyretin amyloidosis, though, is the knowledge that we may be able to use CRISPR injections to treat other genetic disorders that are difficult to target directly, such as heart or brain diseases.

"This is a wonderful day for the future of gene-editing as a medicine," Fyodor Urnov, a UC Berkeley professor of genetics, who wasn't involved in the trial, told NPR. "We as a species are watching this remarkable new show called: our gene-edited future."

Quantcast