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

1)在已建立的纹状体功能障碍动物模型中，采用Fos和γ-氨基丁酸双重免疫组织化学染色方法，观察注射苯丙胺后苍白球(GP)和内侧脚核(EP)内GABA免疫反应神经元是否被激活以表达Fos免疫反应。纹状体内注射针对即刻早期基因c-fos信使RNA的反义寡核苷酸可抑制纹状体传出活动。这种抑制产生了强健的旋转行为和苯丙胺攻击后同侧GP和EP中Fos的非典型表达。定量分析表明，苯丙胺激活的神经元在GP和EP中大部分表达GABA。本研究结果提示，受纹状体输出活动调节的两个核团的投射神经元对…有抑制作用。2)阐明嗜离子谷氨酸受体免疫阳性细胞的形态变化在6-羟基多巴胺损伤的大鼠胚胎腹侧中脑(VM)纹状体内“发育”移植物中，用免疫组织化学方法检测移植后1、4、12周纹状体内移植物中N-甲基-D-天冬氨酸(N-甲基-D-天冬氨酸)受体1亚单位、α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate受体亚单位(GluR1、GluR2/3和GluR4)或酪氨酸羟化酶(TH)的表达。3)研究了多巴胺D_1受体([^&lt；11&gt；C]SCH23390)和D_2受体([^&lt；11&gt；C]雷洛普利)配体和多巴胺前体类似物6-[^&lt；18&gt；F]fluoro-L-3，4-dihydroxyphenylalanine([^&lt；18&gt；F]FDOPA)作为突触前多巴胺能功能的测量，在大鼠前脑束内侧6-羟基多巴胺损毁后的脑内。损伤后2周通过甲基苯丙胺诱导的旋转行为证实单侧损伤，并在静脉注射后进行脑组织解剖分析。在损伤后3周注射每种示踪剂。[^&lt；11&gt；C]雷洛必利，而不是[^&lt；11&gt；C]SCH23390，在患侧纹状体内的蓄积高于非损侧(健侧)。另一方面，[FDOPA]在患侧纹状体和大脑皮层的积聚较少。我们的研究表明，纹状体多巴胺D_2受体表达上调，而与6-羟基多巴胺损伤同侧的纹状体和大脑皮质的FDOPA摄取减少。因此，D_2拮抗剂和FDOPA的结合可能为评估多巴胺耗竭对帕金森病的影响提供一种潜在的有用的方法。较少

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