Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits

Karen Krukowski,Austin Chou,Mary Campbell-Beachler,Tamako Jones,Xi Feng,Katherine Grue,Kristen Sacramento,Gregory Nelson,Maria Serena Paladini,Susanna Rosi,Lara-Kirstie Riparip

doi:10.1038/s41598-018-26039-7

Abstract

Microglia are the main immune component in the brain that can regulate neuronal health and synapse function. Exposure to cosmic radiation can cause long-term cognitive impairments in rodent models thereby presenting potential obstacles for astronauts engaged in deep space travel. The mechanism/s for how cosmic radiation induces cognitive deficits are currently unknown. We find that temporary microglia depletion, one week after cosmic radiation, prevents the development of long-term memory deficits. Gene array profiling reveals that acute microglia depletion alters the late neuroinflammatory response to cosmic radiation. The repopulated microglia present a modified functional phenotype with reduced expression of scavenger receptors, lysosome membrane protein and complement receptor, all shown to be involved in microglia-synapses interaction. The lower phagocytic activity observed in the repopulated microglia is paralleled by improved synaptic protein expression. Our data provide mechanistic evidence for the role of microglia in the development of cognitive deficits after cosmic radiation exposure.

Highlights

Microglia are the main immune component in the brain that can regulate neuronal health and synapse function
In the last decade research has started to focus on how galactic cosmic rays (GCR) can impact the central nervous system (CNS), with much effort devoted to developing mitigating factors that could prevent or rescue the loss of cognitive functions
For the first time we show that a brief microglia depletion after charged particle radiation exposure completely prevents memory deficits measured more than 90 + days later

Summary

Introduction

Microglia are the main immune component in the brain that can regulate neuronal health and synapse function. 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 behavioral and synaptic alterations observed previously correspond with a modified inflammatory response[4] and enhanced microglia activation up to 12 months after exposure[9,12] Taken together, these studies suggest that GCR exposure can impact both neuronal and microglial cell function when radiation-induced cognitive deficits are measured. In line with these results, we and others have shown that microglia depletion at the time of radiation can prevent cognitive decline and dendritic spine loss in the hippocampus after brain only irradiation[17,18]

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