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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)
阪中 雅広  愛媛大学, 医学部, 教授 (60170601)
楊 麗華  愛媛大学, 医学部, 助手 (50346673)
小西 吉裕  愛媛大学, 医学部, 助手 (90170290)
張 波  愛媛大学, 医学部, 助手 (80325373)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥6,100,000 (Direct Cost: ¥6,100,000)
KeywordsMICROGLIA / ESTOSTERONE / AQUAPORIN / ASTROCYTES / NEURON / APOLIPOPROTEINE / L-Ser / L-Ser / progesterone / アストロサイト / マイクログリア / テストステロン / 性ホルモン受容体 / プロゲステロン / RT-PCR / 脳の性差形成 / アクアポーリン / アンドロゲン / アクアポーリン4 / 細胞の生存率 / タンパク質キナーゼC / 神経細胞
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.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report

Research Products

(36 results)

All Other

All Publications (36 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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [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
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K Mori, A Yokoyama, L Yang, L Yang, N Maeda, N Mitsuda, Junya Tanaka: "L-Serine-mediated release of applipoprotein E and lipids from microglial cells"Experimental Neurology. 185. 220-231 (2004)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2003 Annual Research Report
  • [Publications] F.Gu, R.Hata, K.Toku, L.Yang, Y.-J.Ma, N.Maeda, M.Sakanaka, J.Tanaka: "Testosterone upregulates aquaporin-4 expression in cultured astrocytes"Journal of Neuroscience Research. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.-J.Ma, M.Okamoto, F.Gu, K.Obata, T.Matsumoto, J.Desaki, J.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)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wen T-C, Tanaka J, Hata R, Desaki J, Sato K, Nakata K, et al.: "Erythropoietin protects neurons against chemical hypoxia and cerebral ischemic injury by upregulating Bcl-xL expression"J Neurosci Res.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujita H, Zhang B, Sato K, Tanaka J, Sakanaka M: "Expressions of neuropilin-1, neuropilin-2 and semaphorin 3A mRNA in the rat brain after middle cerebral artery occlusion"Brain Res.. 914. 1-14 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Morita F, Wen T-C, Tanaka J, Hata R, Desaki J, Sato K, et al.: "Protective effect of a prosaposin-derived, 18-mer peptide on slowly progressive neuronal degeneration after brief ischemia"J Cereb Blood Flow Metab.. 21. 1295-1302 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugishita H, Kuwabara Y, Toku K, Furuya S, Hirabayashi Y, et al.: "L-serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate dehydrogenase, an enzyme for L-serine biosynthesis"J Neurosci Res.. 64. 392-401 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-03-31   Modified: 2016-04-21  

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