11/16/16  Portland, Ore.

OHSU research provides insight for planning future deep-space missions

Long-term exposure to cosmic radiation could alter the brain and change behavior in astronauts bound for Mars, according to new research led by scientists at OHSU in Portland, Oregon.

The study, published online Oct. 24 in the journal BMC Genomics, used mice to test effects of radiation that go beyond concerns about cancer. Cosmic rays are formed when stars explode outside our solar system and are made of atoms stripped of their electrons moving at nearly the speed of light. Iron-56 ions, in particular, would be an unavoidable fact of life for astronauts on any future mission to Mars.

Researchers used mice to test both short- and long-term effects of radiation.

“Our results imply that the ability of astronauts to distinguish familiar environments from novel environments – and thus, their cognitive ability – is affected on long trips in deep space,” said senior author Jacob Raber, Ph.D., a professor of behavioral neuroscience in the OHSU School of Medicine.

The NASA-funded study suggests that astronauts may experience cognitive impairments that can affect a space mission. A better understanding of the underlying mechanisms might enable the development and testing of potential treatment options, Raber said.

“This study shows that space irradiation causes dose- and time-dependent epigenomic remodeling in the hippocampus that correlates with behavioral changes,” said first author Soren Impey, Ph.D., an associate professor of cell and developmental biology in the OHSU School of Medicine and member of the Oregon Stem Cell Center at OHSU.

As described in a video animation commissioned by the journal, the study found that mice receiving certain doses of cosmic radiation had trouble recognizing new objects in their environments two weeks later. Interestingly, the memory deficit disappeared when the mice were tested at 20 weeks and didn’t follow a typical dose response. The problem was apparent at the lowest and highest doses but not at the intermediate dose.

After radiation, the scientists examined mouse epigenomes – the layer of chemical tags on top of the genome that controls which genes get turned on and off. They found changes – some short-lived, others longer-lasting – to many genes’ methylation status. One of these offered a clue as to why the memory problems weren’t entirely dependent on dose: Compared to the low-dose mice, the intermediate-dose mice had higher levels of a particular epigenetic marker that was associated with increased expression of synapse-related genes that might be involved in repair.

The findings suggest that animals receiving the intermediate dose didn’t suffer memory problems because the brain kicked into gear and healed itself via epigenetic changes. The lower dose wasn’t strong enough to trigger a meaningful response, but was still damaging enough to elicit the cognitive deficit.

“Unfortunately, the low dose is likely to be the level the astronauts would receive on a mission to Mars,” said co-author Mitchell Turker, Ph.D., professor of occupational health sciences and molecular and medical genetics in the OHSU School of Medicine.

Future work into how these brain changes occur could help scientists find ways of monitoring and protecting astronauts in future deep-space missions.

This research was supported by NASA grant NNJ12ZSA001N.

About OHSU

Oregon Health & Science University is a nationally prominent research university and Oregon’s only public academic health center. It serves patients throughout the region with a Level 1 trauma center and nationally recognized Doernbecher Children’s Hospital. OHSU operates dental, medical, nursing and pharmacy schools that rank high both in research funding and in meeting the university’s social mission. OHSU’s Knight Cancer Institute helped pioneer personalized medicine through a discovery that identified how to shut down cells that enable cancer to grow without harming healthy ones. OHSU Brain Institute scientists are nationally recognized for discoveries that have led to a better understanding of Alzheimer’s disease and new treatments for Parkinson’s disease, multiple sclerosis and stroke. OHSU’s Casey Eye Institute is a global leader in ophthalmic imaging, and in clinical trials related to eye disease.