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Open AccessArticle

Neuroprotective and Anti-Inflammatory Effects of Low–Moderate Dose Ionizing Radiation in Models of Alzheimer’s Disease

1
Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Korea
2
Department of Core Research Laboratory, Medical Science Research Institute, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea
3
Department of Occupational Therapy, Konyang University, Daejeon 35365, Korea
4
Department of Radiation Oncology, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea
5
Department of Clinical Pharmacology and Therapeutics, Kyung Hee University School of Medicine, Seoul 02447, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(10), 3678; https://doi.org/10.3390/ijms21103678
Received: 30 April 2020 / Revised: 15 May 2020 / Accepted: 21 May 2020 / Published: 23 May 2020
Alzheimer’s disease (AD) is the most common cause of dementia. The neuropathological features of AD include amyloid-β (Aβ) deposition and hyperphosphorylated tau accumulation. Although several clinical trials have been conducted to identify a cure for AD, no effective drug or treatment has been identified thus far. Recently, the potential use of non-pharmacological interventions to prevent or treat AD has gained attention. Low-dose ionizing radiation (LDIR) is a non-pharmacological intervention which is currently being evaluated in clinical trials for AD patients. However, the mechanisms underlying the therapeutic effects of LDIR therapy have not yet been established. In this study, we examined the effect of LDIR on Aβ accumulation and Aβ-mediated pathology. To investigate the short-term effects of low–moderate dose ionizing radiation (LMDIR), a total of 9 Gy (1.8 Gy per fraction for five times) were radiated to 4-month-old 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD, and then sacrificed at 4 days after last exposure to LMDIR. Comparing sham-exposed and LMDIR-exposed 5XFAD mice indicated that short-term exposure to LMDIR did not affect Aβ accumulation in the brain, but significantly ameliorated synaptic degeneration, neuronal loss, and neuroinflammation in the hippocampal formation and cerebral cortex. In addition, a direct neuroprotective effect was confirmed in SH-SY5Y neuronal cells treated with Aβ1–42 (2 μM) after single irradiation (1 Gy). In BV-2 microglial cells exposed to Aβ and/or LMDIR, LMDIR therapy significantly inhibited the production of pro-inflammatory molecules and activation of the nuclear factor-kappa B (NF-κB) pathway. These results indicate that LMDIR directly ameliorated neurodegeneration and neuroinflammation in vivo and in vitro. Collectively, our findings suggest that the therapeutic benefits of LMDIR in AD may be mediated by its neuroprotective and anti-inflammatory effects. View Full-Text
Keywords: Alzheimer’s disease; low-moderate dose ionizing radiation; radiotherapy; 5XFAD mice; neurodegeneration; neuroinflammation Alzheimer’s disease; low-moderate dose ionizing radiation; radiotherapy; 5XFAD mice; neurodegeneration; neuroinflammation
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Kim, S.; Nam, Y.; Kim, C.; Lee, H.; Hong, S.; Kim, H.S.; Shin, S.J.; Park, Y.H.; Mai, H.N.; Oh, S.-M.; Kim, K.S.; Yoo, D.-H.; Chung, W.K.; Chung, H.; Moon, M. Neuroprotective and Anti-Inflammatory Effects of Low–Moderate Dose Ionizing Radiation in Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 3678.

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