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

大鼠基底节细胞转录因子与磷酸化谷氨酸受体表达的相关性

• 批准号: 14570935
• 负责人: ISHIDA Yasushi
• 金额: $ 2.24万
• 依托单位: (Miyazaki Medical College) University of Miyazaki
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570935/
• 关键词: dopamine; 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)

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

1)本研究应用Fos和γ-氨基丁酸（GABA）双重免疫染色技术，观察了腹腔注射苯丙胺是否能激活苍白球（GP）和脚内核（EP）内GABA免疫反应阳性神经元表达Fos。纹状体传出活性抑制纹状体内注入的反义寡核苷酸针对即时早期基因，c-fos的信使RNA。这种抑制产生了强大的旋转行为和非典型表达的Fos在同侧GP和EP以下安非他明的挑战。定量分析表明，大多数的安非他明激活的神经元在GP和EP表达GABA。本研究结果提示，纹状体输出活动调节的两个核团的投射神经元的抑制。2）为了阐明离子型谷氨酸受体免疫阳性细胞的形态学变化， ...更多信息 在6-羟基多巴胺损伤的胎鼠腹侧中脑（VM）纹状体内移植物中，用免疫组织化学方法检测N-甲基-D-天冬氨酸（NMDA）受体亚单位1（NR 1）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）受体亚单位（GluR 1，GluR 2/3，和GluR 4），或酪氨酸羟化酶（TH）在纹状体内VM移植后1，4，和12周。结果表明，离子型谷氨酸受体在纹状体内VM移植物的发育过程中具有不同的作用。3）我们研究了多巴胺D_1受体（[^<11>C] SCH 23390）和D_2受体（[^<11>C]雷氯必利）的配体以及多巴胺前体类似物6-[^<18>F]氟-L-3，4-二羟基苯丙氨酸（[^<18>F]FDOPA）的PET示踪分布，作为对大鼠内侧前脑束6-羟基多巴胺损伤后突触前多巴胺能功能的测量。在损伤后2周通过甲基苯丙胺诱导的旋转在行为上确认单侧损伤，并在损伤后3周通过静脉注射每种示踪剂后的组织解剖分析大脑。[^<11>C]雷氯必利（而非[^<11>C] SCH 23390）在病变侧纹状体中的蓄积高于非病变侧（完整侧）。另一方面，<18>在损伤侧的纹状体和大脑皮层中发现较低的[^ F]FDOPA积累。我们的研究表明，在纹状体多巴胺D_2受体的上调和减少FDOPA摄取在纹状体和大脑皮质同侧的6-羟多巴胺损害。因此，D_2受体拮抗剂与FDOPA联合应用可能为评价帕金森病多巴胺耗竭效应提供一种潜在的有用方法。少

项目成果

Ishida, Y. et al.: "Changes in dopamine D2 receptors....."Neurodegenerative Diseases. 1(In press). (2004)

Ishida, Y. 等人：“多巴胺 D2 受体的变化......”神经退行性疾病。

Ishida, Y. et al.: "Morphological changes in immunopositive..."Brain Res.. 940. 79-85 (2002)

Ishida, Y. 等人：“免疫阳性的形态变化……”Brain Res.. 940. 79-85 (2002)

Ishida, Y. et al.: "Morphological changes in immunopositive....."Brain Res.. 940. 79-85 (2002)

Ishida, Y. 等人：“免疫阳性的形态变化......”Brain Res.. 940. 79-85 (2002)

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)

NISHIMORI, T.、IKEDA, T.、TERAYAMA, R.、ISHIDA, Y.、NAKAMURA, T.、OTAHARA, N.：“谷氨酸受体拮抗剂对大鼠横断后背角 Fos 样免疫反应性的影响

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.

ISHIDA, Y.、TODAKA, K.、Hashiguchi, H.、TAKEDA, R.、MITSUYAMA、Y.NISHIMORI, T.：“移植胎儿腹侧中脑神经元发育过程中离子型谷氨酸受体亚基免疫阳性细胞的形态变化。