Limits...
Irradiation in adulthood as a new model of schizophrenia.

Iwata Y, Suzuki K, Wakuda T, Seki N, Thanseem I, Matsuzaki H, Mamiya T, Ueki T, Mikawa S, Sasaki T, Suda S, Yamamoto S, Tsuchiya KJ, Sugihara G, Nakamura K, Sato K, Takei N, Hashimoto K, Mori N - PLoS ONE (2008)

Bottom Line: A 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.The 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan. iwata@hama-med.ac.jp

ABSTRACT

Background: Epidemiological 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 findings: A 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/significance: The 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.

Show MeSH

Related in: MedlinePlus

Cognitive impairments in the irradiated adult rats.(A) Spatial working memory in the eight-arm radial maze with 30-sec delay. Total number of revisits to arms from which pellets had already been taken, (i.e., working memory error) is represented as mean±SEM. Irradiated rats (n = 17) showed a higher number of working memory errors than control (sham-irradiated) rats (n = 15). (B): In the probe trials of the Morris water maze, spatial reference memory was intact in the irradiated rats (n = 12). Data are given as means±SEM. **p<0.01 as compared with control (sham-irradiated) rats (n = 12).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2386242&req=5

pone-0002283-g007: Cognitive impairments in the irradiated adult rats.(A) Spatial working memory in the eight-arm radial maze with 30-sec delay. Total number of revisits to arms from which pellets had already been taken, (i.e., working memory error) is represented as mean±SEM. Irradiated rats (n = 17) showed a higher number of working memory errors than control (sham-irradiated) rats (n = 15). (B): In the probe trials of the Morris water maze, spatial reference memory was intact in the irradiated rats (n = 12). Data are given as means±SEM. **p<0.01 as compared with control (sham-irradiated) rats (n = 12).

Mentions: In the sensorimotor gating test, two-way ANOVA revealed a significant effect [F (1, 42) = 47.1, p<0.001] of irradiation exposure on prepulse inhibition (PPI) (Figure 5A), while acoustic response amplitude in the two groups was not different (Figure 5B). PPI deficits in irradiated rats were shown at each level of prepulse intensity (72, 76, and 84 dB) (Figure 5A). In the social interaction test, the time spent in social behavior in the irradiated rats was significantly (t = 3.73, df = 10, p = 0.004) lower than that that in the control rats (Figure 6). In the eight-arm radial maze test, the number of working memory errors in the irradiated rats was significantly (t = −3.63, df = 27.3, p = 0.001) higher than that of control rats (Figure 7A). In contrast, the two groups' times in the probe test of a Morris water maze as an index of spatial reference memory were not different (Figure 7B).


Irradiation in adulthood as a new model of schizophrenia.

Iwata Y, Suzuki K, Wakuda T, Seki N, Thanseem I, Matsuzaki H, Mamiya T, Ueki T, Mikawa S, Sasaki T, Suda S, Yamamoto S, Tsuchiya KJ, Sugihara G, Nakamura K, Sato K, Takei N, Hashimoto K, Mori N - PLoS ONE (2008)

Cognitive impairments in the irradiated adult rats.(A) Spatial working memory in the eight-arm radial maze with 30-sec delay. Total number of revisits to arms from which pellets had already been taken, (i.e., working memory error) is represented as mean±SEM. Irradiated rats (n = 17) showed a higher number of working memory errors than control (sham-irradiated) rats (n = 15). (B): In the probe trials of the Morris water maze, spatial reference memory was intact in the irradiated rats (n = 12). Data are given as means±SEM. **p<0.01 as compared with control (sham-irradiated) rats (n = 12).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2386242&req=5

pone-0002283-g007: Cognitive impairments in the irradiated adult rats.(A) Spatial working memory in the eight-arm radial maze with 30-sec delay. Total number of revisits to arms from which pellets had already been taken, (i.e., working memory error) is represented as mean±SEM. Irradiated rats (n = 17) showed a higher number of working memory errors than control (sham-irradiated) rats (n = 15). (B): In the probe trials of the Morris water maze, spatial reference memory was intact in the irradiated rats (n = 12). Data are given as means±SEM. **p<0.01 as compared with control (sham-irradiated) rats (n = 12).
Mentions: In the sensorimotor gating test, two-way ANOVA revealed a significant effect [F (1, 42) = 47.1, p<0.001] of irradiation exposure on prepulse inhibition (PPI) (Figure 5A), while acoustic response amplitude in the two groups was not different (Figure 5B). PPI deficits in irradiated rats were shown at each level of prepulse intensity (72, 76, and 84 dB) (Figure 5A). In the social interaction test, the time spent in social behavior in the irradiated rats was significantly (t = 3.73, df = 10, p = 0.004) lower than that that in the control rats (Figure 6). In the eight-arm radial maze test, the number of working memory errors in the irradiated rats was significantly (t = −3.63, df = 27.3, p = 0.001) higher than that of control rats (Figure 7A). In contrast, the two groups' times in the probe test of a Morris water maze as an index of spatial reference memory were not different (Figure 7B).

Bottom Line: A 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.The 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan. iwata@hama-med.ac.jp

ABSTRACT

Background: Epidemiological 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 findings: A 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/significance: The 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.

Show MeSH
Related in: MedlinePlus