| Project/Area Number |
12670947
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
ISHIDA Yasushi Miyazaki Medical College, Associate Professor, 医学部, 助教授 (20212897)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMORI Toshikazu Miyazaki Medical College, Professor, 医学部, 教授 (20112211)
HAMAGUCHI Hiroyuki Miyazaki Medical College, Assistant, 医学部, 助手 (40305090)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | dopamine / 6-hydroxydopamine / basal ganglia / microdialysis / antisense oligbdeoxynucleotide / transplantation / transcriptional factor / immunohistochemistry / 6-ヒドロキシドパミン(6-OHDA) |
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| Research Abstract |
1) We examined whether L-DOPA, might increase production of hydroxyl radicals in intact and dopamine-denervated rat striatum. Salicylate trapping combined with in vivo microdialysis provided measurements of 2, 3-dihydroxybenzoic acid (2, 3-DHBA) as a marker of hydroxyl radical production. The results indicated that repeated administration of high dose L-DOPA increased production of hydroxyl radicals in dopamine-denervated striatum.
2) 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
… More
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.
3) To elucidate the morphological changes in immunopositive cells of ionotropic glutamate receptors within 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 (GluRl, 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. Less
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