Low-dose-rate ionizing radiation affects innate immunity protein IFITM3 in a mouse model of Alzheimer’s disease

Abstract

Purpose

Although the adverse health risks associated with low-dose radiation (LDR) are highly debated, relevant data on neuronal function following chronic LDR exposure are still lacking.

Materials and Methods

To confirm the effect of chronic LDR on the progression of Alzheimer’s disease (AD), we investigated changes in behavior and neuroinflammation after radiation exposure in wild-type (WT) and 5xFAD (TG) mice, an animal model of AD. WT and TG mice, classified by genotyping, were exposed to low-dose-rate radiation for 112 days, with cumulative doses of 0, 0.1, and 0.3 Gy, then evaluated using the open-field and Y-maze behavioral function tests. Changes in the levels of APP processing- and neuroinflammation-related genes were also investigated.

Results

No apparent change was evident in either non-spatial memory function or locomotor activity, as examined by the Y-maze and open field tests, respectively. Although chronic LDR did not affect the levels of APP processing, gliosis (Iba1 and GFAP), or inflammatory cytokines (IL-1β, IL-6, and TNF-α), the levels of IFN-γ were significantly downregulated in TG mice following LDR exposure. In an additional analysis, we examined the genes related to IFN signaling and found that the levels of interferon induced transmembrane protein 3 (IFITM3) were decreased significantly in TG mice following LDR with 0.1 or 0.3 Gy.

Conclusions

Therefore, this study revealed the possibility that LDR could affect the progression of AD, which may be associated with decreased IFN-related signaling, especially IFITM3. Our findings suggest that further studies are required regarding the potential role of LDR in the progression of AD.

Keywords:

• Low-dose-rate radiation
• IFITM3
• Alzheimer’s disease
• neuroinflammation
• behavioral evaluation

Author contributions

C.G.L. and J.S.K. designed the experiments and analyzed the data. Y.S. and H.J.L. performed the behavioral studies and molecular analyses, and conceived the experiments, analyzed the data, and wrote the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant of the National Research Foundation of Korea [NRF- 2020M2C8A2069337 and NRF-2020R1C1C1006659] funded by the Korean government Ministry of Science and ICT (MSIT) and 50531-2022 funded by KIRAMS.

Notes on contributors

Yeonghoon Son

Yeonghoon Son, D.V.M., Ph.D., is a senior researcher at the Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Republic of Korea.

Chang Geun Lee

Chang Geun Lee, Ph.D., is a senior researcher at the Research Center, Dongnam Institute of Radiological and Medical Sciences, Republic of Korea.

Joong Sun Kim

Joong Sun Kim, D.V.M., Ph.D., is an associate professor at the College of Veterinary Medicine, Chonnam National University, Republic of Korea.

Hae-June Lee

Hae-June Lee, D.V.M., Ph.D., is a principal researcher at the Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Republic of Korea.