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Zinc functions in the central nervous system

Research Project

Project/Area Number 09672241
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

TAKEDA Atsushi  University of Shizuoka School of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (90145714)

Co-Investigator(Kenkyū-buntansha) 岡田 昌二  静岡県立大学, 薬学部, 教授 (40046256)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordszinc / essential trace element / brain / hippocampus / learning / epilepsy / glutamatergic neuron / neurological disease / 扁桃体 / 生体微量金属 / 神経調節因子 / 神経変性 / 生体必須微量金属 / 嗅覚 / 脳機能 / 亜鉛含有ニューロン
Research Abstract

The brain barrier system, i.e., the blood-brain and blood-cerebrospinal fluid barriers, is important for zinc homeostasis in the brain. Zinc was supplied to the brain via both the barriers. A large portion of zinc serves as zinc metalloproteins in neurons and glial cells. Approximately 10% of the total zinc in the brain, probably ionic zinc, exists in the synaptic vesicles, and may serve as an endogenous neuromodulator in synaptic neurotransmission. The presence of zinc-containing neurons, a subclass of glutamatergic neurons, that sequester zinc in the presynaptic vesicles and release it in a calcium-and impulse-dependent manner has been demonstrated in the brain, especially in the limbic system such as hippocampus and amygdala. Dietary zinc deprivation affected zinc homeostasis in the brain. Vesicular zinc-enriched regions, i.e., the hippocampus, was responsive to dietary zinc deprivation, which caused learning impairment and olfactory dysfunction. The learning impairment was recovered by feeding with zinc-adequate diet. Olfactory recognition was also reversibly disturbed by the chelation of zinc released from amygdalar neuron terminals. Moreover, zinc homeostasis in the brain was affected by seizure in El (epilepsy) mice. The susceptibility to epileptic seizure, which may decrease vesicular zinc, was also enhanced by zinc deficiency. Therefore, zinc homeostasis in the brain is closely related to brain functions. Vesicular zinc may be involved in regulation of excitatory neurotransmission via glutamate. Even in adult animals and probably adult humans, adequate zinc supply is important for brain functions and prevention of neurological diseases.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Atsushi Takeda et al.: "Zinc distribution in the brain of Nagase analbuminemicrat and enlargement of the ventricular system."Brain Research. 769. 193-195 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda et al.: "Zinc transport in the rat olfactory system."Neuroscience Letters. 225. 69-71 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda et al.: "Role of zinc released by stimulation in rat amygdala."Journal of Neuroscience Research. 57. 405-410 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda et al.: "Release of zinc from the brain of El (epilepsy) mice during seizure induction."Brain Research. 828. 174-178 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda et al.: "Relationship between brain zinc metabolism and transient learning impairment of adult rats fed zinc-deficient diet."Brain Research. 859. 352-357 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda: "Movement of zinc and its functional significance in the brain."Brain Research Review. 34. 137-148 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda et al.: "Metallothionein IV"Birkhauser (Basel, Switzerland). 5 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 武田厚司: "バイオメタル-生体調節の多彩な役割と病態-"黒船印刷(静岡). 26 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Mayumi Kawai and Shoji Okada: "Zinc distribution in the brain of Nagase analbuminemic rat and enlargement of the ventricular system."Brain Res.. 769. 193-195 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jinko Sawashita, Atsushi Takeda and Shoji Okada: "Change of zinc distribution in rat brain with increasing age."Dev.Brain Res.. 102. 295-298 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Kazuhiko Goto and Shoji Okada: "Zinc depletion suppresses tumor growth in mice."Biol.Trace Elem.Res.. 59. 23-30 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Miho Ohnuma, Jinko Sawashita and Shoji Okada: "Zinc transport in the rat olfactory system."Neurosci.Lett.. 225. 69-71 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Kazuhiko Goto, Tetsu Sato, Haruna Tamano and Shoji Okada: "Zinc-specific response in metallothionein induction in liver of tumor-bearing mice."J.Trace Elem.Exp.Med.. 10. 243-248 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Harumi Hisada, Shoji Okada, John E.Mata, Patric L.Iversen and Manuchair Ebadi: "Tumor cell growth is inhibited by suppressing metallothionein-I synthesis."Cancer Lett.. 116. 145-149 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Shioji Ishiwatari and Shoji Okada: "In vivo stimulation-induced release of manganese in rat amygdala."Brain Res.. 811. 147-151 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Yuka Kodama, Miho Ohhuma and Shoji Okada: "Zinc transport from the striatum and substantia nigra."Brain Res.Bull.. 47. 103-106 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Harumi Hisada, Atsushi Takeda, Mai Suzuki, Shoji Okada, John E.Mata, Patric L.Iversen and Manuchair Ebadi: "In vivo growth inhibition of leukemia P388 by metallothionein-I antisense oligodeoxyribonucleotide."J.Trace Elem.Exp.Med.. 11. 1-4 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Jinko Sawashita and Shoji Okada: "Manganese concentration in rat brain : manganese transport from the peripheral tissues."Neurosci.Lett.. 242. 45-48 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Attila Devenyi and James R.Connor: "Evidence for non-transferrin mediated uptake and release of iron and manganese in glia cell cultures from hypotransferrinemic mice."J.Neurosci.Res.. 51. 454-462 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Yuka Kodama, Shioji Ishiwatari and Shoji Okada: "Manganese transport in the neural circuit in rat CNS."Brain Res.Bull.. 45. 149-152 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Jinko Sawashita, Sachiyo Takefuta and Shoji Okada: "Distribution of zinc in the substantia nigra of rats treated with 6-hydroxydopamine."Biol.Trace Elem.Res.. 61. 71-78 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Jinko Sawashita, Sachiyo Takefuta and Shoji Okada: "Role of zinc released by stimulation in rat amygdala."J.Neurosci.Res.. 57. 405-410 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Sachiyo Takefuta, Hiromi Ijiro, Shoji Okada and Naoto Oku: "109Cd transport in rat brain."Brain Res.Bull.. 49. 453-457 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Tomoyuki Hanajima, Hiromi Ijiro, Atsushi Ishige, Susumu Iizuka, Shoji Okada, Naoto Oku: "Release of zinc from the brain of El (epilepsy) mice during seizure induction."Brain Res.. 828. 174-178 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Yuka Kodama and Shoji Okada: "Metallothionein induction in rat brain after intrastriatal injection of zinc and cadmium salts."J.Health Sci.. 45. 20-23 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Shioji Ishiwatari and Shoji Okada: "Manganese uptake into rat brain during development and aging."J.Neurosci.Res.. 56. 93-98 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Mai Suzuki, Shoji Okada and Naoto Oku: "65Zn localization in rat brain after intracerebroventricular injection of 65Zn-histidine"Brain Res.. 863. 241-244 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Sachiyo Takefuta, Shoji Okada and Naoto Oku: "Relationship between brain zinc metabolism and transient learning impairment of adult rats fed zinc-deficient diet."Brain Res.. 859. 352-357 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Naoki Sotogaku, Naoto Oku and Atsushi Takeda: "Manganese concentration in mouse brain after intravenous injection."J.Neurosci.Res.. 61. 350-356 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Haruna Tamano, Shuichi Enomoto, Emi Igasaki, Naoto Oku, Norio Itoh, Tomoki Kimura, Keiichi Tanaka and Atsushi Takeda: "Hepatic zinc response via metallothionein induction after tumor transplantation."Biochem.Biophys.Res.Commun.. 270. 1140-1143 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Mai Suzuki, Shoji Okada and Naoto Oku: "Influence of histidine on zinc transport into rat brain."J.Health Sci.. 46. 209-213 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda, Shioji Ishiwatari and Shoji Okada: "Influence of transferrin on manganese uptake in rat brain."J.Neurosci.Res.. 59. 542-552 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda: "Movement of zinc and its functional significance in the brain."Brain Res.Rev.. 34. 137-148 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Takeda et al.: "Movement of zinc and its functional significance in the brain"Brain Research Review. 34. 137-148 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "Relationship between brain zinc metabolism and transient learning impairment of adult rats fed zinc-deficient diet."Brain Research. 859. 352-357 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "^<65>Zn localization in rat brain after intracerebroventricular injection of ^<65>Zn-histidine."Brain Research. 863. 241-244 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "Influence of histidine on zinc transport into rat brain."Journal of Health Science. 46. 209-213 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "Influence of transferrin on manganese uptake in rat brain."Journal of Neuroscience Research. 59. 542-552 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Naoki Sotogaku et al.: "Manganese concentration in mouse brain after intravenous injection."Journal of Neuroscience Research. 61. 350-356 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "Role of zinc released by stimulation in rat amygdala"Journal of Neuroscience Research. 57. 405-410 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "Release of zinc from the brain of El(epilepsy)mice during seizureinduction"Brain Research. 828. 174-178 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Atsushi Takeda et al.,: "Manganese optake into rat brain during development and aging"Journal of Neuroscience Research. 56. 93-98 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "^<109>Cd transport in rat brain"Brain Research Bulletin. 49. 453-457 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "Metallothionein induction in rat brain after intrastriata1 injection of zinc and cadmium Salts"Journal of Health Science. 45. 20-23 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 武田厚司: "脳栄養としてのミネラル"FOOD Style 21. 3. 23-27 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "Metallothionein IV"C.D.Klaassen ed.,Birkhauser. 5 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Atsushi Takeda et al.,: "Zinc transport from the striatum and substantia nigra" Brain Research Bulletin. 47. 103-106 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Atsushi Takeda et al.,: "Distribution of zinc in the substantia nigra of rats treated with 6-hydroxyclopamine" Biological Trace Element Research. 61. 71-78 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Atsushi Takeda et al.,: "Zinc depletion suppresses tumor growth in mice" Biological Trace Element Research. 59. 23-29 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 武田厚司: "脳における微量金属の動態と役割に関する研究" Biomedical Research on Trace Elements. 9. 1-11 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Atsushi Takeda et al.,: "In vivo stimulation-induced release of manganese in rat amygdala" Brain Research. 811. 147-151 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Atsushi Takeda et al.,: "Manganese concentration in rat brain : manganese transport from the peripheral tissues" Nearoscience Letters. 242. 45-48 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 武田厚司: "脳におけるバイオメタルの動態と役割" 山口正義編 黒船出版, 26 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Atsushi Takeda, et al.: "Zinc transport in the rat olfactory system" Neurosci.Lett.225. 69-71 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Atsushi Takeda, et al.: "Tumor cell growth is inhibited by suppressing metallothionein-I synthesis" Cancer Lett.116. 145-149 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Jinko Sawashita, et al.: "Change of zinc distribution in rat brain with increasing age" Dev.Brain Res.102. 295-298 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Atsushi Takeda, et al.: "Zinc distribution in the brain of Nagase analbumiremic rat and enlargement of the ventricular system" Brain Res.769. 193-195 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Atsushi Takeda et al.: "Zinc-specific response in metallothionein induction in liver of twnor-bearing mice" J.Trace Elem.Exp.Med.10. 243-248 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 武田厚司: "においの情報伝達と亜鉛" aromatopia. 6. 36-38 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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