How does space flight affect the brain?

June 12, 2018

Written by: Sarah Reitz

Space has been called the “final frontier”, with government agencies and private companies alike clamoring to learn more about our solar system and beyond. While there are no doubt an endless number of things to study and explore about our universe, one of the more critical questions is how does space travel and extended time spent in space affect our brain? With manned missions to Mars planned for the 2030s by NASA, and even earlier by SpaceX, understanding the effects of space on the brain has become an even more pressing concern. This is in part because any injuries or negative health effects that occur in space, where the closest help is millions of miles away, could have severe consequences for the safety of the mission and the other voyagers. Space is an environment entirely unlike Earth, so it is understandable that our brains — which have adapted and evolved for Earth’s atmosphere — may suffer unintended consequences of long-term exposure to such drastically foreign conditions. But before we can try to prevent these negative outcomes, we first have to understand exactly what these effects are.

The effects of microgravity
One of the major environmental challenges faced during space travel is microgravity. While we sometimes hear that outer space has zero gravity, this is slightly misleading; there are always some slight gravitational effects in space, though they are substantially weaker (0.000001 G) than we experience on Earth (1 G). While microgravity allows astronauts to effortlessly float from one end of the space station to the other, studies have shown that the brain experiences some less-fun side effects. At the subcellular level, a lack of gravity affects both the interior organization of a cell’s organelles as well as its cytoskeletal structures¹. Since these all play crucial roles in multiple biosynthetic pathways, a spatial shift of these structures may have negative consequences on important processes like DNA replication and protein transport. Given that a number of neurons release proteins called neuropeptides as a way to communicate with each other, impairing protein transport may severely impair neuronal communication in the brain.

Additionally, exposure to microgravity may increase oxidative stress in neurons. Oxidative stress occurs when toxic byproducts produced from normal cellular processes build up faster than the cell can get rid of them, which can lead to cell damage or even cell death. Researchers found that neurons in the hippocampus, an area involved in memory processing, of mice exposed to 7 days of microgravity-like conditions had decreased levels of eleven important proteins². This may be caused by the impairment of protein production and transport pathways mentioned earlier. One of the proteins that was decreased after microgravity exposure was Synuclein β, which helps to prevent abnormally formed proteins from aggregating in neurons, where they could cause serious damage. You may have heard of the effects of abnormal protein aggregation in neurons before: this phenomenon occurs in both Parkinson’s and Alzheimer’s disease. Given that exposure to only 7 days of microgravity was enough to decrease Synuclein β in the hippocampus, it is entirely possible that longer exposures (like during months-long flights to reach Mars) may have even more severe effects on neuronal health in this region, leading to cognitive and memory impairments.

On a larger scale, a different study examined the effects of microgravity on overall brain structure and volume. Since only trained astronauts can actually go to space currently, the researchers in this study had to simulate microgravity in their volunteers (who were not astronauts) by keeping them on bedrest with their head tilted -6 degrees downwards for 30 days³. This downward tilt is currently the most accurate way to recreate many of the effects the body experiences in true microgravity⁴. By comparing MRI images taken before and after the 30 days of “microgravity”, they found significant losses of gray matter (or cell body) volume in the hippocampus, frontal lobes, insula, and parahippocampal gyrus. A separate group of researchers who had volunteers complete 70 days of the same head-down bedrest also found the same results⁵. Interestingly, when they imaged the volunteers 12 days after bed rest had ended, the decreases in gray matter were still present. What is even more concerning is that these areas are involved in memory, judgement, awareness, and decision-making — all things that are critical to maintain on space missions. Additionally, the first group found abnormalities within white matter tracts of the brain (which consist of axons, allowing different areas of the brain to communicate with each other) that mirror the abnormalities seen at early stages of Alzheimer’s disease and mild cognitive impairment.

The effects of radiation
Microgravity is not the only thing that people will have to worry about during space travel. Another large concern is exposure to radiation. On Earth, our atmosphere protects us from the worst of space radiation, but as we leave Earth’s atmosphere and travel through space that protection disappears. We already know from radiation therapies used to treat cancer that radiation can have damaging side effects, but now we are beginning to get a better glimpse of what effects space-level doses of radiation have on the brain. To put this into perspective, astronauts are commonly exposed to radiation in space that is equivalent to having anywhere between 150 and 6,000 chest x-rays!

Numerous studies have examined how space-relevant doses of radiation affect neuronal structure in mice. One structure they have been studying are called dendritic spines, which receive incoming signals from other neurons and help to transmit signals to the neuronal cell body. The studies show that the number of dendritic spines on neurons in multiple regions of the brain are significantly reduced nearly 6 weeks after radiation exposure. Additionally, dendritic complexity of neurons in the hippocampus and cortex was significantly decreased after radiation, and more immature dendritic spines were found.  The reduction in dendritic spines may result in reduced neuronal communication and responsivity. It appears that this may be the case, because animals that had the largest reduction in dendritic spines in the hippocampus also had the most significant memory impairments when they were tested after radiation exposure⁶.

These cognitive impairments have been found in multiple studies as well. Mice exposed to just one instance of space-relevant levels of radiation show decreases in both hippocampal-based and cortical-based cognitive abilities. These include things like deficits in recognition, episodic memory, and cognitive flexibility, as well as increased anxiety and depression⁷. Alarmingly, these cognitive deficits were still present when the mice were examined a full year later. This means that even an acute exposure to radiation could have long-lasting or even permanent impacts on a wide range of cognitive abilities.

How can we combat these effects?
As more research uncovers the mechanisms behind the neural consequences of exposure to microgravity and radiation, the possibility of designing therapies to prevent or treat these effects becomes more feasible. In fact, this is already beginning to happen! A study showed that cosmic radiation increased levels of methylated DNA, an epigenetic DNA modification which effectively silences expression of that DNA. This increase in DNA methylation was correlated with impairments in memory. Knowing this, scientists administered treatments to inhibit DNA methylation either before or after exposure to radiation, and found that both treatments prevented the increase in methylated DNA and, arguably more excitingly, prevented the cognitive deficits⁸. Although this is just a single example, it shows that there is huge potential for avoiding many of the negative neural effects of space travel. With scientists working every day on these problems, it’s likely that this will just be one of many breakthroughs in space neuroscience. With the possibility of deep space exploration by humans inching closer and closer to reality, it is critical that we understand how space affects our brain so that we can develop ways to protect our astronauts and ensure that they are as healthy as possible both during their mission and after they return to Earth.

Image References

Cover Image: Image from NASA Image and Video Library, NASA ID iss035e037030 (images-assets.nasa.gov/image/iss035e037030/iss035e037030~orig.jpg)

Figure 1: Image from Li et al. Effect of simulated microgravity on human brain gray matter and white matter — evidence from MRI (2015) PLoS One 10(8):e0135835. (CC BY 4.0)

References

1. He J, Zhang X, Gao Y, Li S, Sun Y. Effects of altered gravity on the cell cycle, actin cytoskeleton and proteome in Physarum polycephalum (2008) Acta Astronautica. 63:915–22.
2. Sarkar P et al. Proteomic analysis of mice hippocampus in simulated microgravity environment (2006) J Proteome Res 5(3):548-553
3. Li et al. Effect of simulated microgravity on human brain gray matter and white matter — evidence from MRI (2015) PLoS One 10(8):e0135835
4. Hargens AR & Vico L. Long-duration bed rest as an analog to microgravity (1985) J Appl Physiol 120(8):891-903
5. Koppelmans et al. Brain plasticity and sensorimotor deterioration as a function of 70 days head down tilt bed rest (2017) PLoS One 12(8):e0182236
6. Parihar VK et al. Cosmic radiation exposure and persistent cognitive dysfunction (2016) Sci Rep 6:34774
7. Parihar VK, Pasha J, Tran KK, Craver BM, Acharya MM, Limoli CL. Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation (2015) Brain Struct Funct. 220(2):1161-71.
8. Acharya MM et al. Epigenetic determinants of space radiation-induced cognitive dysfunction (2017) Sci Rep 7:4285