Elimination of microglia improves cognitive function following cranial irradiation

Elimination of microglia improves cognitive function following cranial irradiation

Cranial irradiation for the treatment of brain cancer elicits progressive and severe cognitive dysfunction that is associated with significant neuropathology. Radiation injury in the CNS has been linked to persistent microglial activation, and we find upregulation of pro-inflammatory genes even 6 we...

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Bibliographic Details
Published in:Scientific reports Vol. 6; no. 1; p. 31545
Main Authors: Acharya, Munjal M., Green, Kim N., Allen, Barrett D., Najafi, Allison R., Syage, Amber, Minasyan, Harutyun, Le, Mi T., Kawashita, Takumi, Giedzinski, Erich, Parihar, Vipan K., West, Brian L., Baulch, Janet E., Limoli, Charles L.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 12-08-2016
Nature Publishing Group
Subjects:
14/19
631/154/555
631/67/1059/485
64/60
82/51
Cancer
Central nervous system
Cognitive ability
Colony-stimulating factor
Cortex (frontal)
Diet
Hippocampus
Humanities and Social Sciences
Inflammation
Irradiation
Learning
Memory
Microglia
multidisciplinary
Neuroprotection
Post-irradiation
Science
Science (multidisciplinary)
Skull
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Summary:Cranial irradiation for the treatment of brain cancer elicits progressive and severe cognitive dysfunction that is associated with significant neuropathology. Radiation injury in the CNS has been linked to persistent microglial activation, and we find upregulation of pro-inflammatory genes even 6 weeks after irradiation. We hypothesize that depletion of microglia in the irradiated brain would have a neuroprotective effect. Adult mice received acute head only irradiation (9 Gy) and were administered a dietary inhibitor (PLX5622) of colony stimulating factor-1 receptor (CSF1R) to deplete microglia post-irradiation. Cohorts of mice maintained on a normal and PLX5662 diet were analyzed for cognitive changes using a battery of behavioral tasks 4–6 weeks later. PLX5622 treatment caused a rapid and near complete elimination of microglia in the brain within 3 days of treatment. Irradiation of animals given a normal diet caused characteristic behavioral deficits designed to test medial pre-frontal cortex (mPFC) and hippocampal learning and memory and caused increased microglial activation. Animals receiving the PLX5622 diet exhibited no radiation-induced cognitive deficits, and exhibited near complete loss of IBA-1 and CD68 positive microglia in the mPFC and hippocampus. Our data demonstrate that elimination of microglia through CSF1R inhibition can ameliorate radiation-induced cognitive deficits in mice.
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ISSN:2045-2322
2045-2322
DOI:10.1038/srep31545