New Drug Prevents Memory Impairment in Mice Exposed to Simulated Deep Space Radiation

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A team of neuroscientists from the University of California, San Francisco, and Loma Linda University has identified the first potential treatment for the brain damage caused by exposure to galactic cosmic rays.

Novel drugs could one day protect astronauts on deep-space missions from dangerous cosmic radiation. Image credit: Jonny Lindner.

Novel drugs could one day protect astronauts on deep-space missions from dangerous cosmic radiation. Image credit: Jonny Lindner.

The next era of human exploration will be as challenging as it is exciting. As we seek to explore planets beyond our own, both the distances traversed and the difficulties faced during the voyage will be new to humankind.

Long space missions, such as the upcoming Mars journey, require a clear understanding of the effects of space exposure on the mental and physical functional capabilities of astronauts.

The psychological stressors that astronauts face during space travel are powerful and varied, including social isolation, altered sleep patterns, and physical space limitations. This is coupled with the direct impact of the adverse environment of space, which includes exposure to galactic cosmic rays (protons, helium nuclei, and high charge and energy nuclei).

Astronauts on deep-space missions will be exposed to levels of cosmic radiation estimated to be 1,000 times higher than what we experience on Earth or even in the International Space Station’s orbit.

University of California, San Francisco Professor Susanna Rosi and co-authors have conducted NASA-funded research for the past four years to understand how cosmic radiation may affect astronauts’ brains.

The researchers have previously found that exposing mice to simulated cosmic radiation causes problems with memory, social interactions, and anxiety, and has linked these symptoms of radiation exposure to activation of cells called microglia — part of the brain’s immune system.

Activated microglia drive brain inflammation similar to what is seen in neurodegenerative disorders such as Alzheimer’s disease, and also seek out and consume synapses, the information-bearing connections between brain cells.

In the new study, the scientists exposed mice for a day to a dose of radiation comparable to what they might experience in deep space. The experiments were conducted at NASA’s Space Radiation Laboratory.

A week later, after being shipped back to the team’s lab, some of the mice were treated for 15 days with a drug called PLX5622.

The irradiated animals initially displayed no cognitive deficits, but after three months they began showing signs of memory impairment.

Normally, when the researchers place mice in a room with a familiar and an unfamiliar object, the animals spend more time exploring the new object. But mice that had been exposed to space radiation three months earlier explored the two objects equally — presumably because they didn’t remember having seen one of the objects just the day before.

Remarkably, the animals that had been treated with PLX5622 soon after being exposed to radiation performed just like healthy mice on the memory task.

The study authors examined the animals’ brains and showed that while the brains of untreated mice were full of activated microglia and had lost significant numbers of synapses, the brains of treated mice looked just like normal.

“By forcing the brain to replace irritable, radiation-exposed microglia with new, healthy microglia, the drug had allowed the animals avoid the cognitive consequences of radiation,” they said.

“This is really neat evidence, first that rebooting the brain’s microglia can protect cognitive function following radiation exposure, and second that we don’t necessarily need to treat immediately following the radiation exposure for the drug to be effective,” Professor Rosi said.

“Similar compounds to PLX5622 are already in clinical trials for multiple forms of human cancer, which suggests that the new findings could soon be translated to human use,” the scientists said.

“Beyond spaceflight, these compounds could potentially be used to prevent cognitive impairments following cancer radiation therapy, or in age-related cognitive impairment — which has also been linked to microglia-driven brain inflammation.”

The study was published in the May 18 issue of the journal Scientific Reports.

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Karen Krukowski et al. 2018. Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits. Scientific Reports 8, article number: 7857; doi: 10.1038/s41598-018-26039-7