title: Low-dose total-body carbon-ion irradiations induce early transcriptional alteration without late Alzheimer's disease-like pathogenesis and memory impairment in mice.
abstract: The cause and risk factors of Alzheimer's disease (AD) are largely unknown. Studies on possible radiation-induced AD-like pathogenesis and behavioral consequences are important because humans are exposed to ionizing radiation (IR) from various sources. It was reported that total-body irradiations (TBI) at 10 cGy of low linear energy transfer (LET) X-rays to mice triggered acute transcriptional alterations in genes associated with cognitive dysfunctions. However, it was unknown whether low doses of IR could induce AD-like changes late after exposure. We reported previously that 10 cGy X-rays induced early transcriptional response of several AD-related genes in hippocampi without late AD-like pathogenesis and memory impairment in mice. Here, further studies on two low doses (5 or 10 cGy) of high LET carbonion irradiations are reported. On expression of 84 AD-related genes in hippocampi, at 4 hr after TBI, 5 cGy induced a significant upregulation of three genes (Abca1, Casp3, and Chat) and 10 cGy led to a marked upregulation of one gene (Chat) and a downregulation of three genes (Apoe, Ctsd, and Il1α), and, at 1 year after TBI, one gene (Il1α) was significantly downregulated in 10 cGy-irradiated animals. Changes in spatial learning ability and memory and induction of AD-like pathogenesis were not detected by in vivo brain imaging for amyloid-β peptide accumulation and by immunohistochemical staining of amyloid precursor protein, amyloid-β protein, tau, and phosphorylated tau protein. These findings indicate that low doses of carbon-ion irradiations did not cause behavioral impairment or AD-like pathological change in mice.
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: Mitsuru
authors.initials: M
authors.lastname: Nenoi
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002244:Carbon / Q000009:adverse effects*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000528:radiation effects; D018499:Linear Energy Transfer; D008279:Magnetic Resonance Imaging; D018782:Maze Learning / Q000528:radiation effects; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; D002244:Carbon