• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2003 Fiscal Year Final Research Report Summary

Regulation of hypothalamic-pituitary-adrenal system for stress response by intestinal microbiota

Research Project

Project/Area Number 13470014
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionKyushu University

Principal Investigator

KUBO Chiharu  Kyushu University, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (80117100)

Co-Investigator(Kenkyū-buntansha) KOGA Yasuhiro  Tokai University School of Medicine, Prof., 医学部, 教授 (60170221)
SUDO Nobuyuki  Kyushu University, Graduate School of Medical Sciences, Assoc.Prof., 大学院・医学研究院, 助教授 (60304812)
Project Period (FY) 2001 – 2003
KeywordsIntestinal microbiota / Stress / Hypothalamic-pituitary-adrenal axis / Germ-free mouse
Research Abstract

Indigenous microbiota have several beneficial effects on host physiological functions ; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiological system response. To test the idea that such microbes may affect the development of neural systems that govern endocrine response to stress, we investigated hypothalamic-pituitary-adrenal(HPA) reaction to stress by comparing germfree(GF), specific pathogen free (SPF), and gnotobiotic mice. Plasma ACTH and corticosterone elevation in response to restraint stress was substantially higher in GF mice than in SPF mice, but not by ether stimulus. Moreover, GF mice also exhibited reduced brain-derived neurotrophic factor expression levels in the cortex and hippocampus relative to SPF mice. The exaggerated HPA stress response by GF mice was reversed by reconstitution with Bifidobacterium infantis. In contrast, monoassociation with enteropathogenic Escherichia coli, but not with its mutant strain devoid of the translocated intimin receptor gene, enhanced such a response to stress. Importantly, the enhanced HPA response of GF mice was partially corrected by reconstitution with SPF feces at an early stage, but not by any reconstitution exerted at a later stage, which thus indicates that exposure to microbes at an early developmental stage is required for the HPA system to become fully susceptible to inhibitory neural regulation. These results suggest that commensal microbiota can affect the postnatal development of HPA stress response in mice.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] H.Nukina, N.Sudo, Y.Aiba, et al.: "Restraint stress elevates the plasma interleukin-6 levels in germ-free mice."Journal of Neuroimmunology. 115. 46-52 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Hirayama, N.Sudo, M.Sueyasu, et al.: "Endogenous glucocorticoids inhibit scratching behavior induced by the administration of compound 48/80."European Journal of Pharmacology. 481. 59-65 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Chida, N.Sudo, J.Sonoda, et al.: "Electric foot-shock stress-induced excerbation of alpha-galactosylceramide-triggered apoptosis in the mouse liver."Hepatology. 39. 1131-1140 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Sudo, Y.Chida, Y.Aiba, et al.: "Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice."Journal of Physiology (London). (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nukina, N.Sudo, Y.Aiba, et al.: "Restraint stress elevates the plasma interleukin-6 levels in germ-free mice."Journal of Neuroimmunology. 115. 46-52 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirayama, N.Sudo, M.Sueyasu, et al.: "Endogenous glucocorticoids inhibit scratching behavior induced by the administration of compound 48/80."European Journal of Pharmacology. 481. 59-65 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Chida, N.Sudo, J.Sonoda, et al.: "Electric foot-shock stress-induced excerbation of alpha-galactosylceramide-triggered apoptosis in the mouse liver."Hepatology. 39. 1131-1140 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Sudo, Y.Chida, Y.Aiba, et al.: "Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice."Journal of Physiology(London). (in Press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2005-04-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi