Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or 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, Tetsuya Ono, Mitsuru Nenoi

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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 11C-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.

Original languageEnglish
Pages (from-to)84-96
Number of pages13
JournalJournal of radiation research
Volume55
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • Alzheimer's disease
  • Alzheimer's disease-like pathogenesis
  • Morris water maze test
  • low dose
  • mice
  • total-body X-irradiation

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

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