title: Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice.
abstract: The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with (11)C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice.
authors.affiliation: Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tanaka
authors.forename: Bin
authors.initials: B
authors.lastname: Ji
authors.forename: Maiko
authors.initials: M
authors.lastname: Ono
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Fang
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Kouichi
authors.initials: K
authors.lastname: Maruyama
authors.forename: Nakako
authors.initials: N
authors.lastname: Izumi-Nakajima
authors.forename: Nasrin
authors.initials: N
authors.lastname: Begum
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
authors.forename: Akira
authors.initials: A
authors.lastname: Fujimori
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Uehara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakajima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ono
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nenoi
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology*; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008137:Longitudinal Studies; D008569:Memory Disorders / Q000209:etiology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology* / Q000503:physiopathology*; D065853:Spatial Learning / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D014965:X-Rays
keywords: Alzheimer's disease; Alzheimer's disease-like pathogenesis; Morris water maze test; low dose; mice; total-body X-irradiation
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