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11.
GM1 ganglioside is believed to be important in promoting the recovery of neurons from injury. The present study assesses the ability of GM1 to repair or prevent the damage of dopamine neurons caused by the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Treatment of mesencephalic cell cultures with 2.5 μM MPP+ resulted in the loss of 30% of tyrosine hydoxylase (TH) immunoreactive neurons. In contrast, cultures administered 100 μM GM1 ganglioside for 3 days after toxin treatment contained nearly control numbers of TH+ neurons (97%). This reparative effect of GM1 was reflected in parallel increases in TH enzyme activity, dopamine and dopac levels. Cultures sustaining greater insult from higher doses of MPP+ (5.0–10.0 μM) did not benefit from ganglioside treatment, suggesting that rescue by GM1 depended on the degree of initial damage to cells. Moreover, the timing of ganglioside treatment was critical; pretreatment with GM1 alone did not prevent or attenuate the damage caused by subsequent incubation in 2.5 μM MPP+. 相似文献
12.
P. Cumming T. K. Venkatachalam S. Rajagopal M. Diksic A. Gjedde 《Synapse (New York, N.Y.)》1994,17(2):125-128
The blood-brain permeabilities of L-[3H]tyrosine and the tyrosine hydroxylase (TH) inhibitor β-[14C]methyl-para-tyrosine ([14C]AMPT) were determined in rat striatum, a brain region rich in TH activity, and in other brain regions containing relatively little TH activity. In striatum, the unidirectional clearance rate (K1) for L-[3H]tyrosine (6.2 ml hg- ?1 min?1) was significantly greater than the rates for L-[14C]AMPT (2.8 ml hg?1 min?1) and D-[14C]AMPT (0.8 ml hg?1 min?1). The apparent volume of distribution (Vf) for L-[14C]AMPT in striatum (72.5 ± 4.0 ml hg-1) did not differ from the Vf in other brain regions. The homogeneous distribution of L-[14C]AMPT in rat brain indicates that labeled AMPT is unsuitable for the study of TH in vivo by quantitative autoradiography. © 1994 Wiley-Liss, Inc. 相似文献
13.
In order to determine whether the lateral ganglionic eminence (LGE) of the fetal telencephalon is the primary source of striatal precursors in striatal transplants and tissue cultures, cells derived exclusively from the LGE of fetal rat brains were transplanted into the quinolinic-acid-lesioned striatum of adult rats. After 2–3 months they produced grafts that were almost entirely AChE-positive as well as DARPP-32-, TH-, and calbindin-immunoreactive. The grafts were integrated into the host striatum so that host corticofugal fiber tracts interdigitated with graft tissues similar to the way they penetrate the gray matter of the normal striatum. Fast Blue dye injected into the ipsilateral globus pallidus of LGE grafted produced retrogradely labeled neurons within the grafts, but Fluorogold dye injected into the ipsilateral substantia nigra did not. In a separate experiment using DARPP-32-immunohistochemistry as a striatal marker, fetal (E16) and neonatal (P2) rat brains showed DARPP-32 immunoreactivity in the LGE but not in the adjacent medial ganglionic eminence (MGE). In summary, both fetal LGE cells and LGE grafts express specific striatal markers, and LGE grafts integrate into the host striatum and innervate the major striatal efferent target within the host brain. These data suggest that the LGE is the origin of cells committed to striatal phenotypes in the developing brain. 相似文献
14.
应用高压液相色谱(PHLC)对42例阳性精神分裂症患者、25例阴性精神分裂症患者及10例健康正常对照组脑脊液中色氨酸(Trytophan,TRP)和酪氢酸(Tyrosine,Tyr)进行测试,其中TRP/Tyr被作为两者竞争指数,结果提示阳性、阴性精神分裂症患者脑脊液中Tyr显著性降低,而TRP则无显著性变化。但发现阳性精神分裂症患者的TRP/Tyr比值显著高于正常对照组,也显著高于阴性精神分裂症患者,本文结合TRP/Tyr的意义与价值进行了讨论。 相似文献
15.
Summary An esthesioneuroblastoma in a 16-year-old male was studied ultrastructurally and immunohistochemically, using antiserum against tyrosine hydroxylase (TH), a rate-limiting enzyme in the catecholamine-synthesizing pathway. Tumor cells were fairly uniform in appearance, showing scantly cosinophilic cytoplasm and round to oval hyperchromatic nuclei, and were arranged in nests and cords of various sizes. Ultrastructurally, individual tumor cells had well-developed cell organelles including polyribosomes, microtubules, intermediate filaments, centrioles, Golgi apparatus and mitochondria. Secretory-like granules were occasionally found, predominantly in the cell processes. Immunohistochemically, many tumor cells were shown to be immunoreactive for TH. This finding strongly suggested that the present tumor was capable of producing catecholamines and that it might be derived from certain sympathetic neuronal cell nests in the superior nasal cavity. 相似文献
16.
Acute neurite retraction, elicited by diverse agents in several neuronal cell types, has been reported to be inhibited by genistein, a kinase antagonist that is relatively (though not absolutely) selective for tyrosine kinases. It was hypothesized that genistein acts upon ssome final common pathway that integrates multiple extrinsic and intrinsic signals to regulate whether neurites will execute a retraction response (J. Neurochem., 61 (1993) 340–343). To define this pathway in more detail, a quantitative study of NG108-15 cell rapid-onset neurites was carried out as they retract in response to lysophosphatidic acid (LPA, 10 μM). Following the application of LPA, most neurites exhibited early morphologic changes between 0.5 and 1.5 min, followed by progressive shortening and eventual retraction, with 50% of neurites completely retracted by 5 min and 80% gone by 10 min. Genistein did not inhibit the formation of subcortical F-actin, nor its functional competence in several assays. Genistein protected neurites when added at any time prior to the onset of the earliest morphologic changes, but failed to block progression when added to neurites that were already undergoing retraction. These findings imply that the final common pathway (i.e. the critical target(s) for genistein) must be activated late, after the increase in F-actin levels has peaked and just before retraction is initiated. 相似文献
17.
低剂量电离辐射对小鼠免疫器官cAMP和儿茶酚胺含量的影响 总被引:2,自引:0,他引:2
本文报道,75mGy/(12.5mGy/min)单次全身X射线照射后9小时用SRBC免疫C57BL/6小鼠,在免疫后4天和7天脾脏、胸腺和下丘脑cAMP含量均降低;而在免疫后4天脾脏去甲肾上腺素、肾上腺素和酪氨酸含量均增高,免疫后7天肾上腺素含量仍持续增高;当连接γ射线65mGy(0.015mGy/min,6h/d)全身照射小鼠后即刻或29小时后免疫,脾脏和下丘脑cAMP含量也均降低。提示,低剂量 相似文献
18.
丘脑底核高频电刺激对大鼠纹状体多巴胺代谢影响的研究 总被引:3,自引:0,他引:3
目的研究丘脑底核(STN)高频电刺激(HFS)对大鼠纹状体多巴胺(DA)代谢的影响。方法给予正常大鼠一侧STN-HFS,应用微透析观察其对纹状体DA及其代谢产物的影响,应用免疫组化观察其对黑质DA能神经元的影响。结果微透析检测发现刺激侧纹状体DA代谢产物明显增高(P<0.05),DA水平无变化(P>0.05);免疫组化检测发现刺激组和对照组酪氨酸羟化酶(TH)阳性神经元数量无差异(损毁侧分别为24.00±6.81、23.43±5.49,P>0.05)。结论STN-HFS可能通过影响黑质-纹状体DA代谢发挥作用,STN-HFS对黑质DA能神经元可能无保护作用。 相似文献
19.
精神分裂症患者致炎性细胞因子和酪氨酸羟化酶mRNA表达水平的研究 总被引:1,自引:1,他引:0
目的探讨精神分裂症的外周神经免疫机制及其与临床症状的关系。方法检测精神分裂症患者致炎性细胞因子白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF—α)以及酪氨酸羟化酶(TH)的mRNA表达水平,采用逆转录-聚合酶链反应及半定量检测技术,分别检测39例精神分裂症患者(患者组)、25例同胞(同胞组)及30名正常对照(对照组)外周血单个核细胞(PBMC)IL-1β、TNF-α及TH基因表达水平,同时应用阳性和阴性症状量表(PANSS)评定精神分裂症患者临床症状。结果患者组、同胞组及对照组IL-1β的mRNA表达水平分别为1.52±1.01、1.52±1.09和0.74±0.38;TNF—α的mRNA表达水平分别为1.18±0.99、1.01±0.87和0.70±0.29;TH的mRNA表达水平分别为0.55±0.33、0.61±0.32和0.28±0.20。患者组和同胞组的IL-1β、TNF—α、TH的mRNA表达水平均明显高于对照组(P〈0.05或P〈0.01)。患者组IL-1β(r=0.420)、TNF—α(r=0.430)的mRNA表达水平与PANSS的-般病理症状分呈正相关(P〈0.01)。同胞组与对照组合并统计,IL-1β与TNF-α的mRNA表达水平呈正相关(r=0.847,P〈0.01);IL-1β与TH的mRNA表达水平呈正相关(r=0.666,P〈0.01)。患者组仅IL-1β与TNF—α的mRNA表达水平呈正相关(r=0.942,P〈0.01)。结论精神分裂症患者PBMC细胞TH、IL-1β和TNF—α的mRNA表达水平高于正常,且与精神分裂症的-般病理症状显著相关。 相似文献
20.
Jordi Ortiz Lawrence W. Fitzgerald Maura Charlton Sarah Lane Louis Trevisan Xavier Guitart William Shoemaker Ronald S. Duman Eric J. Nestler 《Synapse (New York, N.Y.)》1995,21(4):289-298
In previous studies, we have demonstrated that chronic administration of morphine or cocaine produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing actions of these and other drugs of abuse. Since this neural pathway is also implicated in the reinforcing actions of ethanol, it was of interest to determine whether chronic ethanol exposure results in similar biochemical adaptations. Indeed, as seen for chronic morphine and cocaine treatments, we show here that chronic ethanol treatment increased levels of tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, and decreases levels of neurofilament protein immunoreactivity, in the VTA. Also like morphine and cocaine, ethanol increases levels of cyclic AMP-dependent protein kinase activity in the NAc. These actions of ethanol required long-term exposure to the drug, and were in most cases not seen in the substantia nigra or caudate-putamen, components of the nigrostriatal dopamine system studied for comparison. Altered levels of tyrosine hydroxylase in catecholaminergic cells frequently reflect altered states of activation of the cells. Moreover, increasing evidence indicates that ethanol produces many of its acute effects on the brain by regulating NMDA glutamate and GABA receptors. We therefore examined the influence of chronic ethanol treatment on levels of expression of specific glutamate and GABA receptor subunits in the VTA. It was found that long-term, but not short-term, ethanol exposure increased levels of immunoreactivity of the NMDARl subunit, an obligatory component of NMDA glutamate receptors, and of the Glu Rl subunit, a component of many AMPA glutamate receptors; but at the same time, long-term ethanol exposure decreased immunoreactivity levels of the α1 subunit of the GABAA receptor complex. These changes are consistent with an increased state of activation of VTA neurons inferred from the observed increase intyrosine hydroxylase (TH) expression. These results demonstrate that chronic ethanol exposure results in several biochemical adaptations in the mesolimbic dopamine system, which may underlie prominent changes in the structural and functional properties of this neural pathway related to alcohol abuse and alcoholism. © 1995 Wiley-Liss, Inc. 相似文献