著者

Yosuke Kameno Katsuaki Suzuki Tomoyasu Wakuda Kiyokazu Takebayashi Keiko Iwata Kenji J. Tsuchiya Hideo Matsuzaki Shu Takagai Yasuhide Iwata Kazuhiko Nakamura Norio Mori

出版者

Japan Brain Science society

雑誌

脳科学誌 (ISSN:13415301)

巻号頁・発行日

vol.36, pp.32-45, 2011-03-30 (Released:2017-06-01)

参考文献数

32

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Leukemia inhibitory factor-receptor (LIFR) is known to play a major role in neurogenesis promotions and stem cell self-renewal via binding to their ligands, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF). We hypothesized that LIFR may also play a role in the pathogenesis of schizophrenia. To test this, we performed clinical and animal studies. First, we measured the mRNA levels of LIFR, LIF and CNTF in peripheral lymphocytes from drug-naive patients with schizophrenia (n=22) and from age-and gender- matched healthy controls (n=44) using quantitative real-time RT-PCR. Levels of LIFR mRNA in patients with schizophrenia were significantly lower than those of controls. Expression of LIF mRNA was below the detectable level in both patients and controls. Levels of CNTF mRNA were similar between patients and controls. Second, we evaluated behavioral features in heterozygous LIFR knockout (LIFR^<+/->) mice, in which adult neurogenesis is known to be altered. Interestingly, LIFR^<+/-> mice showed dopaminergic hypersensitivity, which was shown by exacerbated methamphetamine-induced hyperlocomotion, compared to wildtype mice. These findings appear to support our hypothesis and suggest that LIFR may play a role in dopaminergic hypersensitivity.

著者

Yasuhide Iwata Shigeyuki Yamamoto Ikuo Tooyama Shu Takagai Kiyokazu Takebayashi Norio Mori

出版者

Japan Brain Science society

雑誌

脳科学誌 (ISSN:13415301)

巻号頁・発行日

vol.37, pp.16-27, 2011 (Released:2017-06-01)

参考文献数

31

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The numbers of brain tumors survivors who receive whole-brain irradiation (WBI) develop progressive cognitive dysfunction. WBI-induced decrease in neurogenesis in hippocampus is involved in the delayed cognitive impairment. Considerable data suggests that the continuous suppression of neurogenesis may be due to the activated microglia. To clarify the mechanisms of the radiation-induced deficits in cognitive function, we studied an early response of the hippocampal proliferating cells to the WBI. Adult cynomolgus monkeys received fractionated WBI with the total dose of 15Gy and 30Gy. The animals were administrated with BrdU to label proliferating cells five days after the WBI and sacrificed on the next day. The density of proliferating cells in the hippocampus was significantly increased (ANOVA, F=23, df=2, 9, p=0.0003). Comparing to the sham-irradiation, proliferation were elevated by 6.3 and 12.6 times with 15Gy and 30Gy, respectively. However, there is no BrdU (+) cells co-labeled with Iba1, which is a marker of microglia. The radiation-induced cell proliferation in the hippocampus may play a contributory role in the pathogenesis of late delayed cognitive dysfunction after the WBI.