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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2020

Open Access 01-12-2020 | Research

Mitigation of helium irradiation-induced brain injury by microglia depletion

Authors: Barrett D. Allen, Amber R. Syage, Mattia Maroso, Al Anoud D. Baddour, Valerie Luong, Harutyun Minasyan, Erich Giedzinski, Brian L. West, Ivan Soltesz, Charles L. Limoli, Janet E. Baulch, Munjal M. Acharya

Published in: Journal of Neuroinflammation | Issue 1/2020

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Abstract

Background

Cosmic radiation exposures have been found to elicit cognitive impairments involving a wide-range of underlying neuropathology including elevated oxidative stress, neural stem cell loss, and compromised neuronal architecture. Cognitive impairments have also been associated with sustained microglia activation following low dose exposure to helium ions. Space-relevant charged particles elicit neuroinflammation that persists long-term post-irradiation. Here, we investigated the potential neurocognitive benefits of microglia depletion following low dose whole body exposure to helium ions.

Methods

Adult mice were administered a dietary inhibitor (PLX5622) of colony stimulating factor-1 receptor (CSF1R) to deplete microglia 2 weeks after whole body helium irradiation (4He, 30 cGy, 400 MeV/n). Cohorts of mice maintained on a normal and PLX5622 diet were tested for cognitive function using seven independent behavioral tasks, microglial activation, hippocampal neuronal morphology, spine density, and electrophysiology properties 4–6 weeks later.

Results

PLX5622 treatment caused a rapid and near complete elimination of microglia in the brain within 3 days of treatment. Irradiated animals on normal diet exhibited a range of behavioral deficits involving the medial pre-frontal cortex and hippocampus and increased microglial activation. Animals on PLX5622 diet exhibited no radiation-induced cognitive deficits, and expression of resting and activated microglia were almost completely abolished, without any effects on the oligodendrocyte progenitors, throughout the brain. While PLX5622 treatment was found to attenuate radiation-induced increases in post-synaptic density protein 95 (PSD-95) puncta and to preserve mushroom type spine densities, other morphologic features of neurons and electrophysiologic measures of intrinsic excitability were relatively unaffected.

Conclusions

Our data suggest that microglia play a critical role in cosmic radiation-induced cognitive deficits in mice and, that approaches targeting microglial function are poised to provide considerable benefit to the brain exposed to charged particles.
Appendix
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Metadata
Title
Mitigation of helium irradiation-induced brain injury by microglia depletion
Authors
Barrett D. Allen
Amber R. Syage
Mattia Maroso
Al Anoud D. Baddour
Valerie Luong
Harutyun Minasyan
Erich Giedzinski
Brian L. West
Ivan Soltesz
Charles L. Limoli
Janet E. Baulch
Munjal M. Acharya
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-020-01790-9

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