Molecular and cellular alterations of the brain in microgravity simulated conditions

Microgravity induces various physiological changes in the brain of astronauts such as fluid shifts and increased intracranial pressure. These alterations can lead to spaceflight-associated neuro-ocular syndrome (SANS), which is characterised by vision deterioration. The brain undergoes several changes as a result of microgravity such as an upward shift in the skull, increases in cerebrospinal fluid (CSF) volume, and grey and white matter volume changes. The impact of this cephalad fluid shift on astronaut cognition remains poorly understood, however cognitive health is crucial in determining mission success during spaceflight. The exact pathophysiological mechanisms of these changes are not fully elucidated, highlighting the need to understand the underlying molecular mechanisms in order to develop counter measurements to maintain cognitive and ophthalmologic health in astronauts. In this work we have analysed the effect of microgravity on several molecular and cellular processes in the brain. Hereto, we used the hindlimb unloading (HLU) mouse model, which mimics the effects of microgravity. We compared HLU mice to control mice and analysed the expression of the water channel protein aquaporin-4 (AQP4), which plays an important role in cerebrospinal fluid dynamics. While the total expression of AQP4 in the brain of mice subjected to simulated microgravity remained unchanged, we observed a trend towards increased AQP4 polarisation in perivascular astrocytic end feet. This finding suggests the potential involvement of AQP4 in fluid dynamics under microgravity conditions. Additionally, we analysed neuronal and synaptic density, and observed a decrease in neuronal density the motor cortex region associated with hind limb movement and in the hippocampus, a region associated with learning and memory formation. These changes could reflect either neuronal loss, or brain tissue deformation as a result of interstitial fluid shifts. Synaptic density remained unaltered. Lastly, we analysed the effect of simulated microgravity on microglia, the resident immune cells of the central nervous system. We observed no quantitative differences, however morphological indications suggest an increased priming of microglia towards activation in simulated microgravity. Overall, our data suggest a possible involvement of AQP4 in brain fluid dynamics and altered neuronal density in conditions of microgravity.