PLoS ONE (May 2008)

Irradiation in adulthood as a new model of schizophrenia.

  • Yasuhide Iwata,
  • Katsuaki Suzuki,
  • Tomoyasu Wakuda,
  • Norihito Seki,
  • Ismail Thanseem,
  • Hideo Matsuzaki,
  • Takayoshi Mamiya,
  • Takatoshi Ueki,
  • Sumiko Mikawa,
  • Takeshi Sasaki,
  • Shiro Suda,
  • Shigeyuki Yamamoto,
  • Kenji J Tsuchiya,
  • Genichi Sugihara,
  • Kazuhiko Nakamura,
  • Kohji Sato,
  • Nori Takei,
  • Kenji Hashimoto,
  • Norio Mori

DOI
https://doi.org/10.1371/journal.pone.0002283
Journal volume & issue
Vol. 3, no. 5
p. e2283

Abstract

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BackgroundEpidemiological studies suggest that radiation exposure may be a potential risk factor for schizophrenia in adult humans. Here, we investigated whether adult irradiation in rats caused behavioral abnormalities relevant to schizophrenia.Methodology/principal findingsA total dose of 15-Gy irradiation in six fractionations during 3 weeks was exposed to the forebrain including the subventricular zone (SVZ) and subgranular zone (SGZ) with male rats in the prone position. Behavioral, immunohistochemical, and neurochemical studies were performed three months after fractionated ionizing irradiation. Three months after fractionated ionizing irradiation, the total numbers of BrdU-positive cells in both the SVZ and SGZ zones of irradiated rats were significantly lower than those of control (sham-irradiated) rats. Hyperactivity after administration of the dopaminergic agonist methamphetamine, but not the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine, was significantly enhanced in the irradiated rats although spontaneous locomotion in the irradiated rats was significantly lower than that of controls. Behavioral abnormalities including auditory sensory gating deficits, social interaction deficits, and working memory deficits were observed in the irradiated rats.Conclusion/significanceThe present study suggests that irradiation in adulthood caused behavioral abnormalities relevant to schizophrenia, and that reduction of adult neurogenesis by irradiation may be associated with schizophrenia-like behaviors in rats.