The Earth’s magnetic field and atmosphere largely protect us from a background level of radiation emanating from cosmic bodies like the sun, solar flares, and exploding stars. This radiation takes the form of ions, highly charged particles of different natural elements. But there’s no way to fully shield against cosmic radiation in a spaceship, so astronauts venturing beyond Earth’s magnetic barriers are vulnerable to radiation-induced health effects. 

Though many studies have investigated the topic from different angles over the years, there has been little consensus on what kinds of space radiation pose serious health risks for astronauts. Detrimental neurological effects of radiation on anxiety, memory, and attention are especially important during long missions in deep space.

Since few individuals have traveled in space, there was a need to parse through the stockpile of conflicting results from ground-based animal studies in order to estimate potential risks to astronauts. Andrew Wyrobek, a biophysicist and retiree affiliate in Biosciences’ Biological Systems and Engineering (BSE) Division, and Tore Straume, a former National Aeronautics and Space Administration (NASA) radiation biologist and current affiliate senior scientist in BSE, conducted a comprehensive evaluation based on advanced modeling and statistics. Their multi-institutional team set out to standardize results from past studies so they could be compared directly, which uncovered previously unseen patterns in the types of radiation exposure that predicted different types of behavioral changes.

For most of the biological effects of space radiation that have been studied—mainly markers for cancer and tissue toxicity—exposure to heavier ions that deposit more energy as they traverse tissues causes more harm than exposure to lighter ions that deposit less energy. This makes sense given the prevailing understanding that radiation induces damage in biological systems by disrupting DNA: the energy deposited by heavier ions disrupts the genetic material inside the cell nucleus, ultimately causing cancer and other serious abnormalities. Yet, while lighter ions deposit less energy as they traverse tissues, they can cause more significant cognitive and behavioral changes than exposure to heavier ions.

Importantly, lighter ions, such as helium, carbon and oxygen ions, abound in space, so understanding the underlying mechanisms of this unexplained, counterintuitive effect would carry significant implications for astronaut safety.

To investigate this poorly understood observation, the team zeroed in on studies that examined how different types of radiation exposure affected performance on standard cognitive tests that measure anxiety, memory, attention, and response to novelty in rodents. They found that animals exposed to radiation from less dense ions generally had worse behavioral deficits than those exposed to a comparable dose of denser ions. 

The stark contrast between these results and those for markers of cancer inspired the researchers to think differently—perhaps the mechanism for radiation-induced behavioral deficits is different from the accepted mechanism for radiation-induced cancer? 

The team analyzed the energetic and physical properties of the ions associated with behavioral deficits. They concluded that, while low levels of ionizing radiation with lighter ions were not powerful enough to cause detectable damage to cell nuclei or DNA, they were strong enough to damage a different structure within the central nervous system. Based on their calculations, this structure is very small—smaller than a synapse or a nucleus—and has biophysical properties resembling that of a plasma membrane. Plasma membranes are structures made of fatty molecules that form crucial barriers around cells and their internal compartments. 

In combination with these analyses, the researchers had a secondary clue that also pointed to the plasma membrane as a potential radiosensitive target: In a previous study, Straume had uncovered that radiation proved lethal to mouse eggs without causing DNA damage within the nucleus, again indicating an alternative mechanism for radiation-induced biological damage.  Furthermore, the dose-response patterns from the studies in mouse eggs closely resembled those of the studies on behavioral deficits. 

In a recent paper published in Life Sciences in Space Research, the researchers tied these two pieces together and presented their hypothesis positing the plasma membrane as a previously unrecognized target for radiation-induced cognitive and behavioral deficits.

“It’s a paradigm shift away from the nucleus, away from DNA, away from chromosomes, towards something small and thin,” said Wyrobek.

Beyond the broadened understanding of how radiation exposure induces damage in living systems, the finding opens up new questions about how the central nervous system repairs and responds to different kinds of damage—which could have implications for aging and related brain diseases. 

The central nervous system, which includes the brain and spinal cord, is made up of a distributed network of neurons and related cells that all contain plasma membranes. Thus, if the new hypothesis is correct, the targets vulnerable to damage from this specific kind of radiation exposure are widely distributed across the complexity of the central nervous system. This provides a plausible mechanistic explanation for how radiation from lighter ions could impact things as complicated as cognition and behavior. 

“I’d be curious to look at the three-dimensional organization of nervous system cells to see how these radiosensitive targets might be connected,” Wyrobek said. “That could then drive prevention or medical therapies.” 

This study, which was funded by NASA, also could help guide risk assessments for human space travel. Some variability in past radiation data may stem from differences in how humans and rodents respond, but this study suggests that differences in the types of radiation measured—such as ion heaviness—could be a more significant factor for cognitive and behavioral changes.

The work lays a new baseline threshold for which kinds of radiation exposure could prove risky for the central nervous system. Going forward, researchers intend to expand on this work in both rodent and human model systems to more precisely define dose response relationships for different behavioral effects.