Nav: Home

Study identifies an enzyme inhibitor to treat Gulf War illness symptoms

June 06, 2017

At least 100,000 military veterans who served in the 1990-1991 Gulf War were exposed to chemical weapons, released into the air after the United States bombed an ammunition depot in Khamisiyah, Iraq. Today, many are still suffering from Gulf War Illness, a mysterious, multi-symptom disease that experts believe is linked to organophosphate nerve agents sarin and cyclosarin.

A new paper by researchers at Drexel University sheds light on the neurological consequences of exposure to low-levels of these nerve agents and suggests that drugs like tubacin could treat some of the toxins' neurological effects. The results were recently published in the journal Traffic.

To model Gulf War Illness, the researchers treated cultures of human and rat neurons with an organophosphate called diisopropyl flurophosphate, which is an analog of sarin. They also pretreated the neurons with stress hormones to better mimic the stressors of war.

Within the neurons, the research team was looking for deficits in the activity of microtubules, hollow cylinders that act as the cell's conveyor belt, which the investigators believe might go awry in Gulf War Illness patients. Organophosphates can affect a variety of proteins and pathways in cells, and the impacts on microtubules and microtubule-related proteins are likely to be many. The researchers wanted to find whether particular microtubule-related deficits could be identified and corrected pharmacologically to improve Gulf War Illness symptoms.

"In addition to being an architectural element that helps to shape the cell, the microtubule also acts as a railway, which transport organelles throughout the cytoplasm," said Peter Baas, PhD, a professor in the Department of Neurobiology and Anatomy at Drexel's College of Medicine. "We hypothesized that toxins would change the typical way microtubules are chemically modified in neurons and that a drug like tubacin could restore those modifications to normal, thereby treating the disease."

Once treated with tubacin, which makes the microtubules more chemically modified, the researchers observed a restoration in everything that went wrong with the microtubules due to the toxin and stressor treatments.

Surprisingly, they also found that once they corrected the microtubule deficit, defects in dopamine release also markedly improved. Fluctuations in dopamine are thought to be connected to many of the neurological symptoms that Gulf War Illness sufferers face, including insomnia, cognitive problems and headaches. This study's results suggest that dopamine alterations after toxin exposure are in part due to changes in microtubules, and restoring microtubule function to a more normal state could help to alleviate symptoms.

"The fact that a microtubule-based therapy would correct the problem with dopamine release is really encouraging," Baas said.

Baas' research group is part of a multi-institution Gulf War Illness Consortium, a group of investigators dedicated to uncovering the source and treatment for Gulf War Illness. As described in the journal Neurology, Drexel University and Boston University recently received funding from the U.S. Department of Defense to create a Gulf War Illness human stem cell repository, to be shared with researchers across the country for a deeper understanding of this disease.

To create the repository, the researchers are taking blood cells from Gulf War veterans and "reprogramming" them into their "pluripotent" state, which can then be transformed into any type of cell, from a kidney to a neuron. These "pluripotent cell lines" will be especially groundbreaking for studying Gulf War Illness, because they preserve the genetic and possibly epigenetic factors specific to disease susceptibility.

For the study published in Traffic, the researchers did not use pluripotent cells lines derived from Gulf War veterans, but said they plan to use veterans' cells in the future for more refined results.

Since the use of organophosphate pesticides is widespread around the world, and growing evidence indicates a link between these pesticides and disorders such as Parkinson's disease, Baas said that a deeper investigation of low-level OP exposure is critical for preventing and treating neurological conditions arising from such exposures, in addition to Gulf War Illness. Baas also noted that the use of sarin is a concern for the growing threat of bioterrorism, so preparedness for treating victims is paramount.

"We're living in an increasingly toxic world," Baas said. "It's likely that this kind of disease is going to repeat itself if we don't educate ourselves as to its causes, as well as how to prevent and treat it."
-end-


Drexel University

Related Neurons Articles:

How do we get so many different types of neurons in our brain?
SMU (Southern Methodist University) researchers have discovered another layer of complexity in gene expression, which could help explain how we're able to have so many billions of neurons in our brain.
These neurons affect how much you do, or don't, want to eat
University of Arizona researchers have identified a network of neurons that coordinate with other brain regions to influence eating behaviors.
Mood neurons mature during adolescence
Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.
Astrocytes protect neurons from toxic buildup
Neurons off-load toxic by-products to astrocytes, which process and recycle them.
Connecting neurons in the brain
Leuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.
The salt-craving neurons
Pass the potato chips, please! New research discovers neural circuits that regulate craving and satiation for salty tastes.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Losing neurons can sometimes not be that bad
Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease.
Neurons that fire together, don't always wire together
As the adage goes 'neurons that fire together, wire together,' but a new paper published today in Neuron demonstrates that, in addition to response similarity, projection target also constrains local connectivity.
Scientists accidentally reprogram mature mouse GABA neurons into dopaminergic-like neurons
Attempting to make dopamine-producing neurons out of glial cells in mouse brains, a group of researchers instead converted mature inhibitory neurons into dopaminergic cells.
More Neurons News and Neurons Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Accessing Better Health
Essential health care is a right, not a privilege ... or is it? This hour, TED speakers explore how we can give everyone access to a healthier way of life, despite who you are or where you live. Guests include physician Raj Panjabi, former NYC health commissioner Mary Bassett, researcher Michael Hendryx, and neuroscientist Rachel Wurzman.
Now Playing: Science for the People

#544 Prosperity Without Growth
The societies we live in are organised around growth, objects, and driving forward a constantly expanding economy as benchmarks of success and prosperity. But this growing consumption at all costs is at odds with our understanding of what our planet can support. How do we lower the environmental impact of economic activity? How do we redefine success and prosperity separate from GDP, which politicians and governments have focused on for decades? We speak with ecological economist Tim Jackson, Professor of Sustainable Development at the University of Surrey, Director of the Centre for the Understanding of Sustainable Propserity, and author of...
Now Playing: Radiolab

An Announcement from Radiolab