Astronaut in Space
© NASA
Three hundred thousand kilometers from Earth, Apollo 17 astronaut Ron Evans retrieves a film cassette from the spacecraft’s exterior as the mission returns from the moon. Astronauts flying through deep space are more exposed to dangerous cosmic radiation than their counterparts in low-Earth orbit.
Just past the confines of Earth's geomagnetic field, deep space gets downright nasty. There, cosmic radiation from solar flares, supernovae, supermassive black holes and other powerful astrophysical phenomena could spark cancer, vision loss and impaired thinking in future astronauts voyaging to the moon, Mars or beyond.

But a new NASA-funded study published in Brain, Behavior and Immunity makes a bold claim: When exposed to cosmic radiation, women may have an innate biological capacity to stave off associated cognitive declines. A team of researchers at the University of California, San Francisco, (U.C.S.F.) and at Brookhaven National Laboratory found female mice somehow kept clear heads after dangerous doses of radiation whereas males developed obvious cognitive impairment. The group may have also discovered the reason why - which could help create "vaccines" to inoculate humans against radiation's worst effects on the brain.

In the study Brookhaven scientists bombarded an equal number of male and female mice with a potent mix of radioactive particles mimicking those that suffuse deep space - such as high-energy atomic nuclei of oxygen, helium and hydrogen. These particles and others like them ping-pong through the void beyond Earth's protective magnetic bubble, and some are even channeled into the Van Allen Belts-a zone of seething radiation that girdles our globe. Only 24 human beings have ever traversed this treacherous territory: the Apollo astronauts, who sped through the belts en route to the moon. Just how deleterious that radiation bath was for each Apollo voyager remains a matter of contentious debate, but on each trip an astronaut only spent about four hours in the belts, and less than two weeks outside of Earth's geomagnetic field. Astronauts on future missions to deep space may have to contend with much longer exposure times.

The Apollo astronauts were also all men - NASA did not send a woman into space until 1983, when Sally Ride launched into Earth orbit onboard the space shuttle Challenger. And no one at all has ventured back into deep space since the final Apollo mission in 1972. "The type of radiation we're looking at, the astronauts on the International Space Station would be protected from," says lead author Karen Krukowski of U.C.S.F.'s Department of Physical Therapy and Rehabilitation Science.

After exposing the mice to a seven-minute session of simulated cosmic radiation at Brookhaven, researchers at U.C.S.F. monitored the mice for months on end, watching for changes in their physiology, genetics and behavior. The females exhibited no discernible cognitive problems but males displayed clear signs of anxiety as well as diminished socialization, memory and problem solving. "What was most striking to us when we looked at the data is that we saw deficits in the males, and the females were protected in all of them," Krukowski says.

Krukowski and her colleagues hypothesize it could come down to sex-based differences between the activity of microglia-protective cells in the central nervous system that, when activated, can spark inflammation in the surrounding tissue. Previous research has suggested female mice possess fewer numbers of activated microglia than their male counterparts do, potentially offering females more protection against inflammation. As a next step, the U.C.S.F. team is now conducting follow-on experiments, suppressing the activity of microglial cells in new groups of irradiated male and female mice to better understand this potential sex-based difference. With further work, this proposed microglial mechanism might someday be exploited to protect men and women alike on deep-space missions.

But some researchers who were not involved with the work are not buying the study's surprising results. According to Francis Cucinotta, a professor of radiation science at the University of Nevada, Las Vegas, and former chief scientist for NASA's Space Radiation Program, most literature on human exposure to radiation shows sex-blind results. "Humans irradiated for brain cancer treatment at much higher doses don't show much difference between males and females," he says. "For A-bomb survivors in Japan, no brain effects were seen except for in utero exposures." Astronauts on space stations - as well as workers at nuclear power plants - also show no discernible sex-linked differences, he notes. Even if the new results from U.C.S.F. and Brookhaven are independently confirmed, Cucinotta adds, "females are definitely higher for cancer risk due to breast and ovarian cancers from radiation exposure - many human and animal studies show this to be true."

Rebecca Oberley-Deegan, a radiation biologist at the University of Nebraska Medical Center, is similarly skeptical of the new results, saying the male mice may have been predisposed to some of the problems later documented by Krukowski and colleagues. Her criticism draws from known sex-based differences in how mice socialize. "While I think that all the correct tests were run for cognition and that proper controls were in place, the authors have a huge problem in their empirical setup: The male mice were fighting throughout the entire experiment while the female mice were not," she says. "It appears that the male mice fought so much that five died as a result, and they all had wounds throughout the experiment. This is very common and generally only littermate males are housed together because they will not fight." Fighting between males from multiple litters, Oberley-Deegan adds, could cause an increase in anxiety and inflammation. "I would not say that these results show conclusively that males are at more risk in developing radiation damage than females," she says. "I would say this data shows that a stressed-out, wounded animal is more vulnerable to radiation damage."

Krukowski confirms not all of the study's male mice shared kinship, but notes this was accounted for: Littermates were only housed together, and any aggressive mice were singled out for separate housing in a solitary but stimulus-rich habitat. Neither mice that were wounded nor those that died during the experiment were used in the subsequent behavioral analyses.

Even with these and other precautions, however, Krukowski and her team acknowledge the question of how humans react to long sojourns in deep space is so multidimensional that any experiment short of actually mounting such missions must be considered preliminary. "Cosmic radiation exposure is only one obstacle astronauts face during deep-space missions," Krukowski says, pointing to other potential troubles such as sleep deprivation and the physiological effects of spending months or years in microgravity-factors that she and her team intend to eventually study in tandem with radiation's effects. "This is a first step in understanding how cosmic radiation can influence cognitive and behavioral domains."