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2003 Fiscal Year Final Research Report Summary

The role of sex steroid on the generation of sex differences in the brain development with special attention to androgen.

Research Project

Project/Area Number 13470335
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionEhime University

Principal Investigator

TANAKA Junya  EHIME UNIV., MEDICINE, PROFESSOR, 医学部, 教授 (70217040)

Co-Investigator(Kenkyū-buntansha) HAPA Ryuji  EHIME UNIV., MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (90258153)
YOKOYAMA Masayoshi  EHIME UNIV., MEDICINE, PROFESSOR, 医学部, 教授 (50116993)
Project Period (FY) 2001 – 2003
KeywordsMICROGLIA / ESTOSTERONE / AQUAPORIN / ASTROCYTES / NEURON / APOLIPOPROTEINE / L-Ser / L-Ser
Research Abstract

1)Microglia and astrocytes were found to express receptors for androgen as revealed by RT-PCR study.
2)Based on comprehensive experiments with RT-PCR technique, testosterone was found to increase the expression of mRNA encoding aquaporin 4 in astrocytes. Not only testosterone but progesterone and dehydrotestosterone also upregulated the expression of aquaporin 4 at both mRNA and protein level. Protein kinase C (PKC) activator phorbol ester abolished the testosterone-induced increase of aquaporin 4. This suggests that the action of androgen is dependent on the action of PKC.
3) Microglia of mesodermal origin have prosperities resembling monocytes/macrophages. We have found that microglia possess a nature as a multipotential neural stem cells. By incubating microglial cells in culture medium containing 70% serum, the cells came to have a nature as undifferentiated stem cells. The stem-like microglia differentiated into neurons or oligodendrocytes after they were transferred into serum-free medium. Testosterone enhanced the transformation of microglial cells into cells with neuroectodermal phenotypes through the undifferentiated cells. Furthermore, testosterone altered the expression pattern of mRNAs encoding GFAP.
4)Microglial cells were found to produce and release lipoproteins containing apolipoprotein E, cholesterol, phospholipids and triglycerides in the presence of L-Ser. Testosterone elicited inhibitory effects on the release of lipoproteins by microglial cells.

  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] K Mori, A Yokoyama, L Yang, L Yang, N Maeda, N Mitsuda, Junya Tanaka: "L-Serine-mediated release of apolipoprotein E and lipids from microglial cells."Experimental Neurology. 185. 220-231 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A Yokoyama, L Yang, S Itoh, K Mori, Junya Tanaka: "Microglia, a potential source of neurons, astrocytes, and oligodendrocytes."Glia. 45. 96-104 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y Kuwabara, A Yokoyama, L Yang, K Toku, K Mori, I Takeda, T Shigekawa, B Zhang, N Maeda, M Sakanaka, Junya Tanaka: "Two populations of microglial cells isolated from rat primary mixed glial cultures."Journal of Neuroscience Research. 73. 22-30 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] F Gu, R Hata, K Toku, L Yang, Y-J Ma, N Maeda, M Sakanaka, Junya Tanaka: "Testosterone upregulates aquaporin-4 expression in cultured astrocytes."Journal of Neuroscience Research. 72. 709-715 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y-J Ma, M Okamoto, F Gu, K Obata, T Matsumoto, J Desaki, Junya Tanaka, M Sakanaka: "Neuronal distribution of EHSH1/inetrsection, a molecular linker between clathrin-mediated endocytosis and signaling pathways."Journal of Neuroscience Research. 71. 468-477 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Ohkubo, Y.-D.Lee, A.Morishima, T.Terasaka, S.Kikkawa, M.Tohyama, M.Sakanaka, J.Tanaka, N.Maeda, M.P.Vitek, N.Mitsuda: "Apolipoprotein E and reelin ligands modulate tau phosphorylation through an apolipoprotein E receptor/disabled-a/glycogen synthase kinase-3b cascade."FASEB Journal. (Internet Journal). 10.1096/fj.02-0434fje (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Mori, E.Ozaki, B.Zhang, L.Yang A.Yokoyama, I.Takeda, N.Maeda, M.Sakanaka, J.Tanaka: "Effects of norepinephrine on rat cultured microglial cells that express α1, α2, β1 and β2 adrenergic receptors."Neuropharmacology. 43. 1026-1034 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wen T-C, Tanaka J, Hata R, Desaki J, Sato K, Nakata K, Ma Y-J, Sakanaka M: "Erythropoietin protects neurons against chemical hypoxia and cerebral ischemic injury by upregulating Bcl-xL expression."Journal of Neuroscience Research. 67. 795-803 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhang B, Yang L, Konishi Y, Maeda N, Sakanaka M, Tanaka J.: "Suppressive effects of phosphodiesterase type IV inhibitors on rat cultured microglial cells : Comparison with other types of cAMP-elevating agents."Neuropharmacology. 42. 262-269 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroki Sugishita, Yasuhide Kuwabara, Kazuko Toku, Lisa Doi, Lihua Yang, Junya Mitoma, Shigeki Furuya, Yoshio Hirabayashi, Nobuji Maeda, Masahiro Sakanaka, Junya Tanaka: "L-Serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate dehydrogenase, an enzyme for L-serine biosynthesis."Journal of Neuroscience Research. 64. 392-401 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K Mon, A Yokoyama, L Yang, L Yang, N Maeda, N Mitsuda, Junya Tanaka: "L-Serine-mediated release of apolipoprotein E and lipids from microglial cells."Experimental Neurology. 185. 220-231 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A Yokoyama, L Yang, S Itoh, K Mori, Junya Tanaka: "Microglia, a potential source of neurons, astrocytes, and oligodendrocytes."Glia. 45. 96-104 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y Kuwabara, A Yokoyama, L Yang, K Toku, K Mori, I Takeda, T Shigekawa, B Zhang, N Maeda, M Sakanaka, Junya Tanaka: "Two populations of microglial cells isolated from rat primary mixed glial cultures."Journal of Neuroscience Research. 73. 22-30 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] F Gu, R Hata, K Toku, L Yang, Y-J Ma, N Maeda, M Sakanaka, Junya Tanaka: "Testosterone upregulates aquaporin-4 expression in cultured astrocytes."Journal of Neuroscience Research. 72. 709-715 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y-J Ma, M Okamoto, F Gu, K Obata, T Matsumoto, J Desaki, Junya Tanaka, M Sakanaka: "Neuronal distribution of EHSH1/inetrsection, a molecular linker between clathrin-mediated endocytosis and signaling pathways."Journal of Neuroscience Research. 71. 468-477 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Ohkubo, Y.-D.Lee, A.Morishima, T.Terasaka, S.Kikkawa, M.Tohyama, M.Sakanaka, J.Tanaka, N.Maeda, M.P.Vitek, N.Mitsuda: "Apolipoprotein E and reelin ligands modulate tau phosphorylation through an apolipoprotein E receptor/disabled-a/glycogen synthase kinase-3b cascade."FASEB Journal. 10.1096/fj(Internet Journal). 02fje-0434fje (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Mon, E.Ozaki, B.Zhang, L.Yang, A.Yokoyama, I.Takeda, N.Maeda, M.Sakanaka, J.Tanaka: "Effects of norepinephrine on rat cultured microglial cells that express α1,α2,β1 and β2 adrenergic receptors."Neuropharmacology. 43. 1026-1034 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wen T-C, Tanaka J, Hata R, Desaki J, Sato K, Nakata K, Ma Y-J, Sakanaka M: "Erythropoietin protects neurons against chemical hypoxia"Journal of Neuroscience Research. 67. 795-803 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhang B, Yang L, Konishi Y, Maeda N, Sakanaka M, Tanaka J.: "Suppressive effects of phosphodiesterase type IV inhibitors on rat cultured microglial cells : Comparison with other types of cAMP-elevating agents."Neuropharmacology. 42. 262-269 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroki Sugishita, Yasuhide Kuwabara, Kazuko Toku, Lisa Doi, Lihua Yang, Junya Mitoma, Shigeki Furuya, Yoshio Hirabayashi, Nobuji Maeda, Masahiro Sakanaka, Junya Tanaka: "L-Serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate dehydrogenase, an enzyme for L-serine biosynthesis."Journal of Neuroscience Research. 64. 392-401 (2001)

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

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Published: 2005-04-19  

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