Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rethinking seizures associated with cardiac disease

09.08.2019

Fly study suggests neuronal gene malfunction, not oxygen deprivation, is behind long QT seizures

Most people with a medical condition called long QT syndrome have a mutation in a gene that causes bouts of fast, chaotic heartbeats. They also experience fainting spells and seizures. The clinical approach has largely assumed that when the heart beats erratically, the brain eventually does not get enough oxygen -- which in turn causes the seizures.


As suggested by its name, mutations in the gene seizure (sei for short) cause flies to become highly sensitive to heat stress. When ambient temperature goes up rapidly, wild type flies are able to escape these unfavorable conditions. In contrast, mutant flies are hypersensitive to heat and start seizing almost immediately. Hill et al. now show that the protective effect of sei comes from its activity in specific populations of neurons and glia cells in the fly brain. Shown are the neurons in the brain (top panel) and the ventral ganglion (bottom panel) (a structure homologous to the spinal cord), which express the sei protein (green). All other neurons are shown in magenta. The nuclei of all cells in the nerve cord are in blue.

Credit: Yehuda Ben-Shahar, Washington University in St. Louis

Research from Washington University in St. Louis finds that mutations of a gene implicated in long QT syndrome in humans may trigger seizures because of their direct effects on certain classes of neurons in the brain -- independent from what the genetic mutations do to heart function. The new work from Arts & Sciences was conducted with fruit flies and is published August 8 in PLOS Genetics.

"This gene seems to be a key factor in the physiological process that protects neurons from starting to fire uncontrollably in response to a rapid increase in temperature, which could lead to paralysis and death," said Yehuda Ben-Shahar, associate professor of biology in Arts & Sciences.

... more about:
»cardiac »flies »fruit flies »glia »nervous system »neurons

Alexis Hill, recently a postdoctoral fellow in the Ben-Shahar laboratory, discovered this unexpected relationship as she probed the nervous system response to acute environmental stress.

Heat in general causes neurons to start firing faster, so the brain is particularly sensitive to overheating. Mammals and other large animals have ways to maintain their internal temperature and protect their brains from heat. But not the fruit fly. With no extra bulk in his tiny body, the only thing a fly can do to regulate temperature is to move from an uncomfortable spot to a comfortable one.

Ben-Shahar had previously published work showing flies that lack a gene called sei could not act to save themselves at temperatures above 25 degrees Celsius (77 Fahrenheit). They had no ability to buffer heat stress, and started having seizures as temperatures increased.

This gene sei -- named by other researchers who had previously discovered its role in seizure activity -- shows up in lots of places in fruit flies: in the neurons responsible for primary communication of both excitatory and inhibitory signals, in the glia cells of the nervous system that support neurons in various ways, and in the heart.

In their new work, Hill and Ben-Shahar were able to show that sei protects against heat-induced hyperexcitability only when it is expressed in a few particular classes of neurons and glia. Knocking down the gene in the heart had no effect on seizure activity.

"The ability of flies to resist the heat is in neurons that release neurotransmitters that make other neurons fire faster, the ones that excite neurons," Ben-Shahar said.

Surprisingly, the study also uncovered a protective role for sei in glia, the other primary cell of the nervous system. Glia have traditionally been overshadowed by the importance of neurons, but in recent years they have been emerging as equally important in maintaining healthy brain functions. The fact that this work identifies a protective role of an ion channel in glia further supports the idea that glia have much broader physiological functions in the nervous system and how it might respond to environmental challenges, the researchers said.

A careful look through the scientific literature reveals many references to seizure associated with long QT syndrome, which afflicts human beings with a genetic mutation to a sei-comparable gene called hERG.

But most clinical practitioners assume that these seizures are a secondary outcome of cardiovascular disease. Ben-Shahar hopes this soon will change.

"If you look at population statistics, there is a much higher incidence of seizures in long QT patients than in the general population," he said. "Because cardiovascular dysfunction can cause all kinds of problems, in the literature right now it is assumed that the seizures are secondary -- that because the people have a sick heart they end up developing seizures and other things.

"It's possible, based on our data, that it's two independent effects. Because if the mutation is affecting the function of the gene in the heart, it will affect the function in the neurons.

"And in flies, it's not going to kill neurons," Ben-Shahar said. "We know that we can completely eliminate this gene from the fly genome -- and flies will develop normally, mostly. Yet they become extremely sensitive to environmental (conditions). It's possible that that's exactly what's happening in people -- that it's completely independent."

Media Contact

Talia Ogliore
talia.ogliore@wustl.edu
314-935-2919

 @WUSTLnews

http://www.wustl.edu 

Talia Ogliore | EurekAlert!
Further information:
https://source.wustl.edu/2019/08/rethinking-seizures-associated-with-cardiac-disease/
http://dx.doi.org/10.1371/journal.pgen.1008288

Further reports about: cardiac flies fruit flies glia nervous system neurons

More articles from Life Sciences:

nachricht Rising water temperatures could endanger the mating of many fish species
03.07.2020 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Moss protein corrects genetic defects of other plants
03.07.2020 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

Im Focus: AI monitoring of laser welding processes - X-ray vision and eavesdropping ensure quality

With an X-ray experiment at the European Synchrotron ESRF in Grenoble (France), Empa researchers were able to demonstrate how well their real-time acoustic monitoring of laser weld seams works. With almost 90 percent reliability, they detected the formation of unwanted pores that impair the quality of weld seams. Thanks to a special evaluation method based on artificial intelligence (AI), the detection process is completed in just 70 milliseconds.

Laser welding is a process suitable for joining metals and thermoplastics. It has become particularly well established in highly automated production, for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

 
Latest News

Rising water temperatures could endanger the mating of many fish species

03.07.2020 | Life Sciences

Risk of infection with COVID-19 from singing: First results of aerosol study with the Bavarian Radio Chorus

03.07.2020 | Studies and Analyses

Efficient, Economical and Aesthetic: Researchers Build Electrodes from Leaves

03.07.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>