2005 Fiscal Year Final Research Report Summary
Role of sensory neurons to gender difference in the responses against stress.
| Project/Area Number |
16591810
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
UCHIBA Mitsuhiro Kumamoto University, University Hospital, Instructor, 医学部附属病院, 助手 (90315292)
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| Co-Investigator(Kenkyū-buntansha) |
OKAJIMA Kenji Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (60152295)
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| Project Period (FY) |
2004 – 2005
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| Keywords | gender / CGRP / sensory neurons / gastric mucosal injury / knockout mouse / activated leukocyte / denervation |
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| Research Abstract |
Sensory neurons play a critical role in reducing stress-induced gastric mucosal injury by releasing calcitonin gene-related peptide (CGRP) through an increase in gastric mucosal levels of prostacyclin (PGI2). Since estrogen enhances the nerve growth factor-mediated CGRP production in sensory neurons, we hypothesized that stress-induced gastric mucosal injury occurs less in females than in males. Gastric ulcer index (UI), gastric myeloperoxidase (MPO) activity, gastric tissue levels of CGRP and 6-keto-PGF1α, a stable metabolite of PGI2, were determined in male and female wild-type (CGRP+/+) mice, CGRP knockout (CGRP-/-) mice and Wistar rats subjected to stress. Results : UI and MPO activities were lower and gastric tissue levels of 6-keto-PGF1α were higher in females than in males in CGRP+/+ mice, while there were no such gender differences in CGRP-/- mice. Gastric tissue levels of CGRP in rats were significantly higher in females than in males. Gender differences seen in CGRP+/+ mice were also observed in rats, but they were eliminated by pretreatment with capsazepine (CPZ), a vanilloid receptor antagonist, and by ovariectomy (OVX) in female rats. Reversal of gender differences by OVX was not observed in estradiol-treated female rats. Levels of CGRP mRNA in dorsal root ganglion neurons isolated from female rats were decreased by OVX and these decreases were reversed by estradiol replacement. in conclusions, estrogen-mediated increases in CGRP levels in sensory neurons might contribute to reduce stress-induced gastric mucosal injury by attenuating inflammatory responses. This might at least partly explain the gender difference observed in the development of stress-induced gastric mucosal injury in rodents.
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