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Modulation of Neuroinflammation by Low-Dose Radiation Therapy in an Animal Model of Alzheimer's Disease.
Yang, Eun-Jeong; Kim, Hyunju; Choi, Yunjung; Kim, Hak Jae; Kim, Jin Ho; Yoon, Jeongmin; Seo, Young-Seok; Kim, Hye-Sun.
Afiliação
  • Yang EJ; Department of Pharmacology and Biomedical Sciences, Seoul National University, College of Medicine, Seoul, Republic of Korea; Neuroscience Research Center, Seoul National University, College of Medicine, Seoul, Republic of Korea.
  • Kim H; Department of Pharmacology and Biomedical Sciences, Seoul National University, College of Medicine, Seoul, Republic of Korea; Neuroscience Research Center, Seoul National University, College of Medicine, Seoul, Republic of Korea.
  • Choi Y; Department of Pharmacology and Biomedical Sciences, Seoul National University, College of Medicine, Seoul, Republic of Korea.
  • Kim HJ; Department of Radiation Oncology, Seoul National University, College of Medicine, Seoul, Republic of Korea; Department of Radiation Oncology, Seoul National University College of Medicine & Hospital, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic
  • Kim JH; Department of Radiation Oncology, Seoul National University, College of Medicine, Seoul, Republic of Korea.
  • Yoon J; Department of Radiation Oncology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates; Department of Global Operations and Business Development, Seoul National University Hospital, Seoul, Republic of Korea.
  • Seo YS; Department of Radiation Oncology, Chungbuk National University Hospital, Seowon-gu, Cheongju, Korea. Electronic address: newbranch78@gmail.com.
  • Kim HS; Department of Pharmacology and Biomedical Sciences, Seoul National University, College of Medicine, Seoul, Republic of Korea; Neuroscience Research Center, Seoul National University, College of Medicine, Seoul, Republic of Korea; Seoul National University Bundang Hospital, Seongnam, Sungnam, Bundang
Int J Radiat Oncol Biol Phys ; 111(3): 658-670, 2021 11 01.
Article em En | MEDLINE | ID: mdl-34144146
PURPOSE: Recently, several studies have reported that low-dose radiation therapy (RT) suppresses the release of proinflammatory cytokines in inflammatory-degenerative disorders, including Alzheimer disease (AD). AD is the most common cause of dementia, and neuroinflammation is one of the major contributing factors in AD pathogenesis. Therefore, low-dose RT may be used clinically for treating AD. However, the appropriate doses, effects, and underlying mechanisms of RT in AD have not been determined. In this study, we aimed to determine the appropriate RT dose and schedule for AD treatment and to investigate 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 5x Familial AD (5xFAD) mice, a well-known animal model of AD, by comparing the effects of a low total dose with low dose per 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 CD68 dual immunostaining was significantly reduced by LD-LDRT and LMD-CDRT in the hippocampus of 5xFAD mice. Moreover, LD-LDRT and LMD-CDRT decreased the amyloid plaque burden in the hippocampus of 5xFAD mice and attenuated their 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 of amyloid plaques by regulating neuroinflammation in the late stage of AD in 5xFAD mice, with an efficacy equivalent to that of LMD-CDRT. Furthermore, the findings suggest that compared with LMD-CDRT, LD-LDRT may facilitate accessible and convenient treatment in clinical trials.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Idioma: En Ano de publicação: 2021 Tipo de documento: Article