2021년 10월 연구원 논문
김현주 연수연구원 (신경과학연구소)
Modulation of Neuroinflammation by Low-Dose Radiation Therapy in an Animal Model of Alzheimer’s Disease
International Journal of Radiation Oncology, Biology, Physics
▸Purpose: Recently, several studies have reported that low-dose radiation therapy (RT) suppresses the release of proinflamma-tory cytokines in inflammatory-degenerative disorders, including Alzheimer disease (AD). AD is the most common cause ofdementia, and neuroinflammation is one of the major contributing factors in AD pathogenesis. Therefore, low-dose RT maybe used clinically for treating AD. However, the appropriate doses, effects, and underlying mechanisms of RT in AD have notbeen determined. In this study, we aimed to determine the appropriate RT dose and schedule for AD treatment and to investi-gate the therapeutic effects and mechanisms of low-dose RT in AD. ▸Methods and Materials: We first determined the proper dose and schedule for RT in late-stage AD using 8- to 9-month-old 5xFamilial AD (5xFAD) mice, a well-known animal model of AD, by comparing the effects of a low total dose with low doseper fraction (LD-LDRT, 5⨉0.6 Gy) with those of a low moderate total dose with conventional dose per fraction (LMD-CDRT, 5⨉2 Gy). ▸Results: LD-LDRT and LMD-CDRT were found to reduce the levels of the proinflammatory cytokines CD54, IL-3, CXCL9/10, and CCL2/4 in the hippocampus of 5xFAD mice. Furthermore, increased microgliosis assessed using Iba-1 and CD68dual immunostaining was significantly reduced by LD-LDRT and LMD-CDRT in the hippocampus of 5xFAD mice. More-over, LD-LDRT and LMD-CDRT decreased the amyloid plaque burden in the hippocampus of 5xFAD mice and attenuatedtheir cognitive impairment; these effects persisted for 4 to 5 weeks. ▸Conclusions: The present study showed that LD-LDRT alleviates cognitive impairments and prevents the accumulation ofamyloid plaques by regulating neuroinflammation in the late stage of AD in 5xFAD mice, with an efficacy equivalent to thatof LMD-CDRT. Furthermore, the findings suggest that compared with LMD-CDRT, LD-LDRT may facilitate accessible andconvenient treatment in clinical trials.