2000 Fiscal Year Final Research Report Summary
Functional correlations between hypothalamus and splenic sympathetic nervous system under environmental stress and immune response
| Project/Area Number |
10470015
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | kanazaw University |
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Principal Investigator |
SHIMIZU Nobuaki Kanazawa Univ., Fac., Eng., Prof., 工学部, 教授 (50019634)
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| Co-Investigator(Kenkyū-buntansha) |
KATAFUCHI Toshihiko Kyushu Univ., Grad.School of Med.Sci., Associate Prof., 大学院・医学系研究科, 講師 (80177401)
HAYASHI Yoshishige Kanazawa Univ., Fac., Eng., Prof., 工学部, 教授 (60019750)
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| Project Period (FY) |
1998 – 2000
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| Keywords | immobilization stress / 8-OH-DPAT / serotonin / noradrenaline / microdialysis / splenic sympathetic nerve / hypothalamus / frontal cortex |
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| Research Abstract |
Various kinds of stressful stimuli stimulate central sympathetic outflow to peripheral nerve endings, and the autonomic nervous system is thought to serve as a major communication link between the brain and the immune system. The purpose of this research project was to study the possible mechanisms of the hypothalamic function in modulating the peripheral immune system, and verify the direct linkage between the activity of the splenic sympathetic nerve and the cytotoxicity of NK cells in the spleen. To further clarify the functional roles of transmitter substances on the behavioral abnormalities caused by the emotional stress, the effects of immobilization stress on food intake were also investigated.
1) Significant reduction of daily food intake was observed after 2 hr immobilization and injection of methysergide antagonized the immobilization-induced anorexia for 3 hr. Brain microdialysis clarified the immobilization induced serotonin release in the hypothalamus. Injection of 8-OH-DPA
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T itself had no effect on basal release of serotonin, while it significantly blocked the immobilization induced serotonin release in the lateral hypothalamus and stress induced anorexia These results suggest that immobilization-induced anorexia is mediated at least in part through serotonergic mechanisms in the hypothalamus.
2) In vivo microdialysis technique was adopted for chronic monitoring of splenic noradrenaline (NA) release in rats. Immobilization stress caused a rapid increase in the NA release release to about 800% of basal release in conjunction with suppression of NK cell activity in the spleen. Surgical denervation of the splenic sympathetic nerve significantly attenuated the elevated level of NA and also inhibited the immobilization-induced suppressive effect on NK activity. Intracerebroventricular injection of corticotropin releasing factor (2 μg/rat) or intraperitoneal injection of interleukin 1-β ( 50 ng/kg), which suppress the NK activity, significantly increased the splenic NA release. These results suggest that NA has an important role in the control of neuroimmunomodulation in the spleen. Less
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