April 23, 2013
Human Spaceflight: Elevated Risk Of Neurological Degeneration As A Result Of Microgravity
April Flowers for redOrbit.com - Your Universe Online
A small device in the payload of the space shuttle Atlantis that housed a set of biological samples was the target of a team of eager US Army researchers when the shuttle touched down at Cape Canaveral in the summer of 2011. The mission was the end of the shuttle program, but the beginning of two years of study on those samples. The team presented their results at the Experimental Biology 2013 conference this past week in Boston, shedding light on how the human immune system responds to stress and assaults while in space — and perhaps here on Earth as well.
"Weakening of the immune system associated with spaceflight is an area that needs a thorough investigation," said Marti Jett, director of the Integrative Systems Biology Program at the U.S. Army Medical Command. "Astronauts subjected to microgravity have shown a significant immune weakening. Furthermore, microgravity has been shown to enhance bacterial virulence while depressing the immune response."
Atlantis' four-person crew completed many tasks on that last mission, among them were experiments on human cells using a common component of an Earth-dwelling microorganism that plays a role in septic shock. The Army team, led by Rasha Hammamieh, designed, remotely oversaw and replicated the experiments on Earth under normal gravity conditions. Hammamieh is the deputy director of the Integrative Systems Biology Program, which is based at the U.S. Army Center for Environmental Health Research at Fort Detrick in Maryland.
"There's an increased risk of infection due to altered bacterial growth in microgravity. Wounds heal poorly in microgravity. So the question investigated was 'In what way does the host response to pathogen differ in microgravity versus on Earth?'" Hammamieh explained. The initial goal of the research team was to investigate the molecular cascade of events that occur in human endothelial cells in response to exposure to the endotoxin lipopolysaccharide, or LPS, from the cell wall of gram-negative bacteria.
The cells were not touched by the LPS for the first six days of the mission, but even during that time they showed genomic responses typical of immune dysfunction to the zero-gravity conditions. "And so, when we added the agonist, they didn't respond very well," Jett said. The cells were so occupied by the gravity situation that they barely put up a fight against the bacteria. The cells' poor response "suddenly reminded us of something we'd seen previously," Jett said.
A previous study by the team concerned Army Rangers. The researchers took blood samples from the special forces participants at the beginning, middle and end of their intensive training program. Those samples were exposed to pathogens to see if battlefield conditions affected immune responses. The results of that study were published last year in the journal Genes & Immunology.
"We found that they weren't responding normally at all. We saw what maybe one could guess in retrospect that you would see, which was that the immune system was involved in the stress of being a Ranger, and when we added these pathogens — the virus, bacteria and toxin — in separate experiments, they didn't respond to them. And we saw something very similar to that in space. The cells were probably preoccupied with the response to microgravity, and, therefore, when exposed to LPS, yes, there was a response, but it certainly wasn't comparable to what we were seeing on the ground."
In the samples aboard Atlantis, there was a diminished capacity of the cells to activate the normal immune response in terms of pathogen processing, according to the researchers. Angeogenesis and vaculogenesis were altered by reduced gravity, as well as promoting genes involved in rheumatoid arthritis, tumor growth and wound repair. The team says that this suggests an elevated risk of neurological degeneration and other problems as a result of microgravity.
The results of both the spaceflight study and Rangers study have drawn the interest of those studying immune response in people exposed to other high-stress conditions, such as Wall Street executives and CEOs, according to Jett. "The core motivation was to try to understand why there is not a good immune response in terms of healing and preventing illness in space — why healing is compromised — and it just ends up coming back to maybe broader strokes to what we see on Earth as well," Jett said.
WHY THIS TOXIN?
Out of all the possible pathogens, the team chose LPS for the space experiments because it is the most common endotoxin and because it impairs the wound-healing process. Left untreated, gram-negative bacteria infection can cause septic shock, also known as sepsis.
"Every year, severe sepsis strikes about 750,000 Americans. It's been estimated that between 28 and 50 percent of these people die - far more than the number of U.S. deaths from prostate cancer, breast cancer and AIDS combined," Hammamieh said.
Approximately $17 billion is spent annually to treat the rising number of sepsis cases in the US. LPS-induced endotoxemia is the most common form of infection after burns, and it's the leading cause of postsurgical deaths.
"Our research seeks diagnostic, therapeutic and prognostic markers of LPS infection in the healthy cells and the cells immunocompromised by microgravity. Our high-dimensional, -omics approach results in deluge of data," explained Hammamieh. This flood of data promises to hold the key to therapy for this complex disease.
Reduced gravity enhances bacterial activity, making it possible that "the host responses in microgravity may adapt novel healing mechanisms, or the assaults may find unconventional pathways to trigger the damage. The understanding of these paradigms can potentially enlighten the ground-based LPS therapy."
BIOLOGICAL RESEARCH IN SPACE
The team had only six months to prepare for the launch after securing the project's financing in early 2011. However, they work as a well oiled machine — having conducted systems biology work since the late 1990s. According to Jett, the team already had a workable plan in mind. The challenge was adapting it to work in space.
"One of the complexities was to be prepared to repeat the entire setup in case the launch did not occur on the designated day. Because our cell cultures required three days to prepare for launch, we had to have cultures ready for the backup dates even while preparing as the shuttle was on the launch pad," she said. "Our technical staff got just two hours of sleep the night before the launch, since they had to prepare for the next two launch dates in case of delay. It was exhausting, exciting and an unbelievable experience."
The logistics of landing were nearly as challenging as the launch. A shuttle landing site is never a "sure thing" because of weather, so one team member was dispatched to Florida and one to California.
"We had one person in the air going to Cape Canaveral. Dr. Hammamieh was in the airport ready to step on the plane to go to L.A. and asked, 'If I hear it's landing at Cape Canaveral, can I step off?' And then, just before she stepped through the door of the plane and they were going to close it, she got the message 'It's landing at Cape Canaveral!' and she got off. It was a crazy time. It was really fun."