Elimination of microglia improves cognitive function following cranial irradiation
Open accessAbstract
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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Microglial depletion strategies can restore similar multicellular deficits and rescue impaired cognitive performance in mouse models of CRCI.
“For example, microglial depletion strategies can restore similar multicellular deficits and rescue impaired cognitive performance in mouse models of CRCI (Acharya et al., 2016; Gibson et al., 2019),”
From Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation (2022) · cites this paper as Acharya et al., 2016
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- Authors
- Acharya, M. M., Green, K. N., Allen, B. D., Najafi, A. R., Syage, A., Minasyan, H., Le, M. T., Kawashita, T., Giedzinski, E., Parihar, V. K., West, B. L., Baulch, J. E., & Limoli, C. L.
- Affiliations
- University of California, Irvine (US)
- Plexxikon (United States) (US)
- Corresponding author
- Acharya, Munjal M.
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-08-12
- Volume
- 6
- Issue
- 1
- Pages
- 31545-31545
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4981848
- OpenAlex
- W2507620027
- Cited by
- 259
- References
- 37
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 28 · 2023: 15 · 2022: 30 · 2021: 31 · 2020: 41 · 2019: 30 · 2018: 25 · 2017: 18
- FWCI
- 13.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR001414, KL2TR001416, AG016573, AG00538)
- University of California, Irvine (P50AG016573)
- National Institute on Aging (P01AG000538, AG-016573, AG 00538, P50AG016573, T32AG000096)
- National Institute of Neurological Disorders and Stroke (NS089575, R01NS074388, R01NS089575, R01NS083801)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- microglia depletion, cranial irradiation, radiation-induced cognitive dysfunction, CSF1R inhibition, PLX5622, microglial activation, neuroinflammation, medial prefrontal cortex, hippocampus, learning and memory, neuroprotection
- MeSH terms
- Animals, Behavior, Animal, Brain Neoplasms, Cognition, Hippocampus, Male, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Cranial Irradiation, Microglia, Mice
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