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


ABSTRACT: Alzheimer's disease (AD) is the most common cause of dementia. The neuropathological features of AD include amyloid-? (A?) 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 A? accumulation and A?-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 A?-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 A? 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 A?1-42 (2 ?M) after single irradiation (1 Gy). In BV-2 microglial cells exposed to A? and/or LMDIR, LMDIR therapy significantly inhibited the production of pro-inflammatory molecules and activation of the nuclear factor-kappa B (NF-?B) 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.

SUBMITTER: Kim S 

PROVIDER: S-EPMC7279400 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Kim Sujin S   Nam Yunkwon Y   Kim Chanyang C   Lee Hyewon H   Hong Seojin S   Kim Hyeon Soo HS   Shin Soo Jung SJ   Park Yong Ho YH   Mai Han Ngoc HN   Oh Sang-Muk SM   Kim Kyoung Soo KS   Yoo Doo-Han DH   Chung Weon Kuu WK   Chung Hyunju H   Moon Minho M  

International journal of molecular sciences 20200523 10


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  ...[more]

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