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Correlation between cellular expression of transcription factors and of phosphorylated glutamate receptors in rat basal ganglia

Research Project

Project/Area Number 14570935
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research Institution(Miyazaki Medical College) University of Miyazaki

Principal Investigator

ISHIDA Yasushi  University of Miyazaki, Professor, 医学部, 教授 (20212897)

Co-Investigator(Kenkyū-buntansha) ABE Hiroshi  University of Miyazaki, Assistant, 医学部, 助手 (20344848)
HASHIGUCHI Hiroyuki  University of Miyazaki, Assistant, 医学部, 講師 (40305090)
TAKEDA Ryuichiro  University of Miyazaki, Assistant, 医学部, 助手 (90336298)
NISHIMORI Toshikazu  Miyazaki Medical College, Professor, 医学部, 教授 (20112211)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsdopamine / 6-hydroxydopamine / basal ganglia / antisense / oligodeoxynucleotide / transplantation / transcriptional factor / phosphorylated glutamate receptor / immunohistochemistry / 6-ヒドロキンドーパミン(6-OHDA)
Research Abstract

1)Double immunostaining for Fos and γ-aminobutyric acid (GABA) was used in a previously established animal model of striatal dysfunction to examine whether GABA-immunoreactive neurons in the globus pallidus (GP) and entopeduncular nucleus (EP) are activated to express Fos immunoreactivity by intraperitoneal injection of amphetamine. Striatal efferent activity was suppressed by intrastriatal infusions of antisense oligodeoxynucleotide targeted to the messenger RNA of the immediate early gene, c-fos. This suppression produced robust rotational behavior and an atypical expression of Fos in the ipsilateral GP and EP following amphetamine challenge. Quantitative analysis revealed that a majority of the amphetamine-activated neurons in the GP and EP express GABA. The present results suggest an inhibition by projection neurons of the two nuclei that are regulated by striatal output activity.
2)To elucidate the morphological changes in immunopositive cells of ionotropic glutamate receptors with … More in intrastriatal "developing" grafts of fetal ventral mesencephalon (VM) in 6-hydroxydopamine-lesioned rats, immunohistochemistry was performed to detect cells expressing N-methyl-D-aspartate (NMDA) receptor subunit 1 (NR1), the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits (GluR1, GluR2/3, and GluR4), or tyrosine hydroxylase (TH) in the intrastriatal VM grafts at 1, 4, and 12 weeks following transplantation. The results suggest that the ionotropic glutamate receptors have differential roles during the developmental period of the intrastriatal VM grafts.
3)We studied the PET tracer distributions of ligands for dopamine D_1 receptors ([^<11>C]SCH23390) and D_2 receptors ([^<11>C]raclopride) and of the dopamine precursor analog 6-[^<18>F]fluoro-L-3,4-dihydroxyphenylalanine ([^<18>F]FDOPA) as a measurement of presynaptic dopaminergic function, in the brain after 6-hydroxydopamine lesions of the medial forebrain bundle in rats. The unilateral lesions were confirmed behaviorally by methamphetamine-induced rotation at 2 weeks postlesion, and the brains were analyzed by tissue dissection following i.v. bolus of each tracer at 3 weeks postlesion. [^<11>C]Raclopride, but not [^<11>C]SCH23390, showed a higher accumulation in the striatum on the lesion side compared with that on the non-lesioned (intact) side. On the other hand, a lower accumulation of [^<18>F]FDOPA was found in the striatum and cerebral cortex on the lesion side. Our studies demonstrate upregulation in dopamine D_2 receptors in the striatum and a decrease in FDOPA uptake in both the striatum and cerebral cortex ipsilateral to the 6-hydroxydopamine lesions. Therefore the combination of a D_2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Ishida, Y. et al.: "Amphetamine-induced Fos expression....."Exp.Neurol.. 175. 275-281 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishida, Y. et al.: "Morphological changes in immunopositive....."Brain Res.. 940. 79-85 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishida, Y. et al.: "Conditioned-fear stress increases....."Synapse. 45. 46-51 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishida, Y. et al.: "Fos expression in GABAergic cells....."Synapse. 46. 100-107 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishida, Y. et al.: "Changes in dopamine D2 receptors....."Neurodegenerative Diseases. 1(In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] ISHIDA, Y., DENOVAN-WRIGHT, E., HEBB, M.O., ROBERTSON, H.A.: "Amphetamine-induced Fos expression is evident in γ-aminobutyric acid neurons in the globus pallidus and entopeduncular nucleus in rats treated with intrastriatal c-fos antisense oligodeoxynucleotide."Exp.Neurol.. 175. 275-281 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] ISHIDA, Y., TODAKA, K., HASHIGUCHI, H., TAKEDA, R., MITSUYAMA, Y.NISHIMORI, T.: "Morphological changes in immunopositive cells of ionotropic glutamate receptor subunits during the development of transplanted fetal ventral mesencephalic neurons."Brain Res.. 940. 79-85 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] ISHIDA, Y., HASHIGUCHI, H., TAKEDA, R., ISHIZUKA, Y., MITSUYAMA, Y., KANNAN, H, NISHIMORI, T., NAKAHARA, D.: "Conditioned-fear stress increases Fos expression in brainstem monoaminergic and GABAergic neurons of the locus coeruleus and dorsal raphe nuclei."Synapse. 45(1). 46-51 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] ISHIDA, Y., NAKAHARA, D., HASHIGUCHI, H., NAKAMURA, M., EBIHARA, K., TAKEDA, R., NISHIMORI, T., NIKI, H.: "Fos expression in GABAergic cells and cells immunopositive for NMDA receptors in the inferior and superior colliculi following audiogenic seizures in rats."Synapse. 46(2). 100-107 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] NISHIMORI, T., IKEDA, T., TERAYAMA, R., ISHIDA, Y., NAKAMURA, T., OTAHARA, N.: "Effect of glutamate receptor antagonists on Fos-like immunoreactivity in the dorsal horn following transection of the rat sciatic nerve."Brain Res.. 934(1). 81-86 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] ABE, H., ISHIDA, Y., IWASAKI, T.: "Perirhinal N-methyl-D-aspartate and muscarinic systems participate in object recognition in rats."Neuroscience Letters. 356(3). 191-194 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] ISHIDA, Y., HASHIGUCHI, H., TAKEDA, R., ABE, H., KAWAI, K., MAGATA, Y., SAJI, H.: "Changes in dopamine D_2 and 6-[^<18>F]fluoro-L-3,4-dihydroxyphenylalanine uptake in the striatum and cerebral cortex after 6-hydroxydopamine lesions of the medial forebrain bundle in rats."Neurodegenerative Diseases. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishida, Y. et al.: "Amphetamine-induced Fos expression..."Exp.Neurol.. 175. 275-281 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishida, Y. et al.: "Morphological changes in immunopositive..."Brain Res.. 940. 79-85 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishida, Y. et al.: "Conditioned-fear stress increases..."Synapse. 45(1). 46-51 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishida, Y. et al.: "Fos expression in GABAergic cells..."Synapse. 46(2). 100-107 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishida, Y. et al.: "Changes in dopamine D2 receptors..."Neurodegenerative Diseases. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishimori, T. et al.: "Effect of glutamate receptor..."Brain Res.. 934(1). 81-86 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishida, Y. et al.: "Amphetamine-induced Fos expression is evident in GABA neurons・・・"Exp. Neurol.. 175(1). 275-281 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishida, Y. et al.: "Morphological changes in immunopositive cells of ionotropic・・・"Brain Res.. 940(1-2). 79-85 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishida, Y. et al.: "Conditioned-fear stress increases Fos expression in brainstem・・・"Synapse. 45(1). 46-51 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishimori, T. et al.: "Effect of glutamate receptor antagonists on Fos-like・・・"Brain Res.. 934(1). 81-86 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 武田龍一郎他: "パーキンソン病モデルラットにおける痛覚過敏"Progress in Medicine. 22(11). 2905-2909 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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