Low-dose total-body carbon-ion irradiations induce early transcriptional alteration without late Alzheimer's disease-like pathogenesis and memory impairment in mice

Bing Wang, Kaoru Tanaka, Bin Ji, Maiko Ono, Yaqun Fang, Yasuharu Ninomiya, Kouichi Maruyama, Nakako Izumi-Nakajima, Nasrin Begum, Makoto Higuchi, Akira Fujimori, Yoshihiko Uehara, Tetsuo Nakajima, Tetsuya Suhara, Mitsuru Nenoi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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 carbon-ion 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.

Original languageEnglish
Pages (from-to)915-926
Number of pages12
JournalJournal of Neuroscience Research
Volume92
Issue number7
DOIs
Publication statusPublished - 2014 Jul

Keywords

  • Alzheimer's disease-like pathogenesis
  • Behavioral impairment
  • Carbon-ion irradiation
  • Gene expression
  • Hippocampi

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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