Grant-in-Aid for Scientific Research (A)
|Allocation Type||Single-year Grants |
|Research Institution||Tokyo Medical and Dental University |
HIROKAWA Katsuiku Tokyo Medical and Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (00014093)
KITAGAWA Masanobu Tokyo Medical and Dental University, Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助教授 (10177834)
IKEDA Toru Tokyo Medical and Dental University, Graduate School, Lecturer, 大学院・医歯学総合研究科, 講師 (00211029)
UTSUYAMA Masanori Tokyo Medical and Dental University, Graduate School, Assistant, 大学院・医歯学総合研究科, 助手 (70167287)
|Project Period (FY)
2000 – 2003
Completed (Fiscal Year 2003)
|Budget Amount *help
¥33,950,000 (Direct Cost: ¥29,900,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2003: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2002: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2001: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2000: ¥16,400,000 (Direct Cost: ¥16,400,000)
|Keywords||Brain / Immune system / Cytokine / Cytokine receptors / Infection / Thymus / GMF / Immunological restoration. / Glia Maturation Factor β / T細胞分化 / 老化 / ストレス / 複合感染 / LPS / リステリア菌 / インフルエンザウイルス|
Immune system works as major defense corps against infection and at the same time collaborates with neuro-endocrine systems to play a pivotal role in the maintenance of internal environment. The neuro-endocrine system mainly influences the immunological functions through various hormones and autonomic nerves and the immune system mainly affects the neuro-endocrine functions through various cytokines. The present, study reports 8 results, as followings, mainly focusing on the neuro-endocrine-immune interaction with aging.
1. HypothaLamus is not only a center for endocrine system but also controls thymic functions. The early decline of thymic function is partly under the control of hypothalamic function.
2. LPS injection was employed as an infection model, causing cytokine production and expression of cytokine receptors in the immune system. The study revealed that various cytokine receptors were expressed in the brain after LPS injection and the pattern of expression was different by the
type of cytokines and age of mice. The results partly explain the difference in clinical signs between young and elderly people at the time of infection.
3.'The lvels of various monoamines in the brain were depressed in rats under chronic stress. An immunosuppressive drug, cyclosporine A enhanced the levels of monoamines and acted like anti-depressant.
4. Glia factor β (GMFβ) is known to play a role in the maturation of glia in the brain. The present study reyealed that GMFβ was also produced by thymic epithelial cells and played an important role in CD4 T cell differentiation. GMFβ is another common factor between the brain and the immune system.
5. Diethylstilbestrol, a synthetic estrogen, influences the immune system at a very low dose, but the effect is different by age and sex of mice, and dose of hormone. The results again suggest the endocrine-immune interaction is not monotonous and changes by age and sex.
6. Immunological restoration can be observed by administration or feeding of Japanese herbal medicine and the effect is especially prominent in aged mice.
7. Methods of immunological restoration in the elderly animals are composed of two types. One is stimulation of pre-existent immune cells by various stimulants. The other is implantation of young or active cells/tissues. Several methods were introduced considering human application.
8. Japanese herbal medicines are effective in the restoration of immune functions of aged animals. The study revealed, that one of them is also effective in the improvement of monoamine levels in the brain of aged mice (unpublished data). Less