What happens to your brain on the way to Mars

Abstract

As NASA prepares for the first manned spaceflight to Mars, questions have surfaced concerning the potential for increased risks associated with exposure to the spectrum of highly energetic nuclei that comprise galactic cosmic rays. Animal models have revealed an unexpected sensitivity of mature neurons in the brain to charged particles found in space. Astronaut autonomy during long-term space travel is particularly critical as is the need to properly manage planned and unanticipated events, activities that could be compromised by accumulating particle traversals through the brain. Using mice subjected to space-relevant fluences of charged particles, we show significant cortical- and hippocampal-based performance decrements 6 weeks after acute exposure. Animals manifesting cognitive decrements exhibited marked and persistent radiation-induced reductions in dendritic complexity and spine density along medial prefrontal cortical neurons known to mediate neurotransmission specifically interrogated by our behavioral tasks. Significant increases in postsynaptic density protein 95 (PSD-95) revealed major radiation-induced alterations in synaptic integrity. Impaired behavioral performance of individual animals correlated significantly with reduced spine density and trended with increased synaptic puncta, thereby providing quantitative measures of risk for developing cognitive decrements. Our data indicate an unexpected and unique susceptibility of the central nervous system to space radiation exposure, and argue that the underlying radiation sensitivity of delicate neuronal structure may well predispose astronauts to unintended mission-critical performance decrements and/or longer-term neurocognitive sequelae.

Fig. 1. Behavioral deficits measured 6 weeks after charged particle exposure.

(A) Performance on a NOR task reveals significant decrements in recognition memory indicated by the reduced discrimination of novelty. (B) Performance on an OiP task shows significant decrements in spatial memory retention, again indicated by a markedly reduced preference to explore novelty. *P = 0.05, **P = 0.01, ***P = 0.001, analysis of variance (ANOVA).

Fig. 2. Reduced dendritic complexity of neurons in the prelimbic layer of the mPFC 8 weeks after HZE particle irradiation.

Digitally reconstructed images of EGFP-positive mPFC neurons before (0 cGy) and after (30 cGy) irradiation showing dendrites (green) and spines (red). Quantification of dendritic parameters (bar charts) shows that dendritic branching and length are significantly reduced after low-dose (5 and 30 cGy) exposure to oxygen (¹⁶O) or titanium (⁴⁸Ti) particles. *P = 0.05, **P = 0.01, ANOVA.

Fig. 3. Reductions in dendritic spine density in the mPFC after HZE particle exposure.

Representative digital images of 3D reconstructed dendritic segments (green) containing spines (red) in unirradiated (top left panel) and irradiated (bottom panels) brains. Dendritic spine number (left bar chart) and density (right bar chart) are quantified in charged particle–exposed animals 8 weeks after exposure. *P = 0.05, **P = 0.01, ANOVA.

Fig. 4. Correlation of spine density with DI.

Dendritic spine density (per 1.3 mm²) is plotted against the corresponding performance of each animal on the OiP task. (A and B) Reduction in spine number after irradiation is correlated with reduced DI for novelty after exposure to 5 or 30 cGy of ¹⁶O (A) or ⁴⁸Ti (B) charged particles. The correlation between spine density and DI is significant for the 30 cGy ⁴⁸Ti data (green circles; P = 0.016).

Fig. 5. Changes in PSD-95 synaptic puncta in the mPFC 6 weeks after exposure to 5 or 30 cGy of ¹⁶O or ⁴⁸Ti charged particles.

Fluorescence micrographs show that irradiation leads to increased expression of PSD-95 puncta (bottom) in mPFC neurons after irradiation compared to controls (top left). Quantified PSD-95 puncta (bar chart) in the mPFC. *P = 0.05, **P = 0.01, ANOVA.