Dataset Information

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]

PMID: 32456197

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Project description:Following nuclear accidents and the increasing use of radionuclides, environmental radiation radiological protection is a source of major concern, particularly in the context of low doses. Ionizing radiation (IR) may lead to genetic mutations, chromosomal rearrangements and epigenetic modifications. The present study focuses on the in vivo effects of low to moderate doses of IR on zebrafish early embryonic development. The effects of IR on the transcriptome were studied at the shield stage (6 hours post-fertilization, hpf) and at dose rates from 50 mGy/h to 0.005 mGy/h. The effects on the methylome by whole genome bisulfite sequencing were investigated at the same stage and at dose rates of 50 mGy/h and 5 mGy/h.IR exposure impacted the expression of genes involved in germ layers specification during gastrulation of zebrafish embryos. Moreover, changes in mitochondrial energetic metabolism were detected at all dose rates. Different transcriptomic responses were observed between groups irradiated at the two highest dose rates, 50 mGy/h and 5 mGy/h and those irradiated at the three lower dose rates. However, the transcriptomic analysis revealed an impact of IR on development, neurogenesis and muscular development at 50 mGy/h, 5 mGy/h and 0.5 mGy/h. The global level of methylation was not changed after exposure to IR, and no widespread changes in transposable elements were detected. Rather, we observed that IR induced loci specific demethylation in the promoter of genes involved in development, neurogenesis and myogenesis. Interestingly, this promoter hypomethylation was equally associated with a change in gene expression. In this study, both DMR and gene expression analysis pointed toward a specific deregulation of genes involved in development, neurogenesis and myogenesis. The modification of the methylation pattern in promoters of genes involved in central nervous system development and muscle development seems to be responsible of transcriptomic changes. This study confirms previous results obtained at later developmental stages, showing that neurogenesis and muscle development were also impacted at 50 mGy/h, 5 mGy/h and 0.5 mGy/h with phenotypic alterations in terms of muscle histology and swimming behaviour. This suggests that early developmental perturbations are predictive of functional defects at later developmental stages.

Dataset Information

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

Publications

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

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