2003 Fiscal Year Final Research Report Summary
Correlation between cellular expression of transcription factors and of phosphorylated glutamate receptors in rat basal ganglia
| Project/Area Number |
14570935
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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) University of Miyazaki |
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Principal Investigator |
ISHIDA Yasushi University of Miyazaki, Professor, 医学部, 教授 (20212897)
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| 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)
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| Project Period (FY) |
2002 – 2003
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| Keywords | dopamine / 6-hydroxydopamine / basal ganglia / antisense / oligodeoxynucleotide / transplantation / transcriptional factor / phosphorylated glutamate receptor / immunohistochemistry |
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| 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
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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
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Research Products
(12 results)
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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).
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「研究成果報告書概要(欧文)」より
