Mitigation of helium irradiation-induced brain injury by microglia depletion

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 a...

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Bibliographic Details
Published in:	Journal of neuroinflammation Vol. 17; no. 1; pp. 159 - 18
Main Authors:	Allen, Barrett D, Syage, Amber R, Maroso, Mattia, Baddour, Al Anoud D, Luong, Valerie, Minasyan, Harutyun, Giedzinski, Erich, West, Brian L, Soltesz, Ivan, Limoli, Charles L, Baulch, Janet E, Acharya, Munjal M
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 19-05-2020 BioMed Central BMC
Subjects:	Alpha particles Animal cognition Animals Behavior Brain Brain - radiation effects Brain injury Care and treatment Cognition Cognitive ability Cognitive disorders Cognitive Dysfunction - etiology Cognitive function Colony-stimulating factor Cortex (frontal) Cosmic background radiation Cosmic radiation Cosmic Radiation - adverse effects Diet Dosimetry Electrophysiology Excitability Glial stem cells Health aspects Helium Helium - toxicity Hippocampus Inflammation Laboratories Male Mice Microglia Neural stem cells Oxidative stress Physiological aspects PLX5622 Post-irradiation Postsynaptic density proteins Radiation injuries Radiation Injuries, Experimental - pathology Risk factors Space irradiation Synaptic density United States United States > US Neuron morphology Space irradiation Electrophysiology Inflammation Spine density Cognitive function PSD-95 Cosmic radiation PLX5622 Microglia
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Summary:	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. 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 ( He, 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. 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. 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.
ISSN:	1742-2094 1742-2094
DOI:	10.1186/s12974-020-01790-9