AGING AND 6 HYDROXYDOPAMINE NEUROTOXICITY

衰老与 6 羟多巴胺神经毒性

• 批准号: 6887738
• 负责人: WAYNE A CASS
• 金额: $ 18.1万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6887738
• 关键词: 6 hydroxydopamine; Parkinson' s disease; aging; amphetamines; chordate locomotion; corpus striatum; disease /disorder model; dopamine; high performance liquid chromatography; immunocytochemistry; laboratory rat; microdialysis; neuropharmacology; neurotoxicology; neurotrophic factors; potassium ion; substantia nigra; tyrosine 3 monooxygenase

DESCRIPTION: (Verbatim from the Applicant's Abstract) The nigrostriatal dopamine (DA) system of the brain plays a major role in the control of movement. A gradual loss of nigrostriatal DA neurons occurs during normal aging in humans, and many elderly persons display one or more of the signs of Parkingson's disease without having the disease. This may indicate that these people have a greater than normal loss of nigrostriatal DA. An animal model of aging with a partial loss of DA neurons (ICV injection of 6-hydroxydopamine, 6-OHDA) is currently being developed by the applicant. The experiments in the present proposal will use this model to determine the extent of spontaneous recovery of presynaptic dopaminergic functioning in young, middle-aged and aged rats. In addition, the effects of the potent dopaminergic factor glial cell line-derived neurotrophic factor (GDNF) will also be examined in this model. It is hypothesized that the nigrostriatal DA system in aged rats will have a reduced capacity to recover from the neurotoxic effects of 6-OHDA compared to young rats. It is further hypothesized that GDNF will be less effective in aged animals compared to young animals both in its ability to protect against 6-OHDA and to promote recovery after the lesion. The first specific aim will examine spontaneous recovery in young (4 months old) middle-aged (14 months old), and aged (24 months old) male and female Fischer-344 rats following partial bilateral lesions with 6-OHDA. Locomotor activity, basal levels and evoked overflow of DA and its metabolites in the striata (as measured with microdialysis), and tyrosine hydroxylase immunohistochemistry studies will be carried out at several time points after the lesion to determine extent of recovery. Post-mortem measurements of tissue monoamines will be analyzed as well. The second specific aim will evaluate the ability of GDNF to prevent or reduce 6-OHDA-induced changes in locomotor activity and presynaptic dopaminergic function in the three age groups, while the third specific aim will examine the ability of GDNF to promote behavioral and neurochemical recovery from the lesion in the three age groups. The results of these experiments will help determine if the nigrostriatal DA system of the aging brain has the same capacity to recover from a neurotoxic insult as that of younger animals, and will begin to evaluate age-related differences in response of nigrostriatal DA neurons to neurotrophic factors.

描述：（摘自申请人摘要）黑质纹状体

项目成果

Progress in understanding basal ganglia dysfunction as a common target for methamphetamine abuse and HIV-1 neurodegeneration.

在理解基底神经节功能障碍作为甲基苯丙胺滥用和 HIV-1 神经变性的共同目标方面取得的进展。

• DOI: 10.2174/157016207780636515
• 发表时间: 2007
• 期刊: Current HIV research
• 影响因子: 1
• 作者: Theodore,Shaji;Cass,WayneA;Nath,Avindra;Maragos,WilliamF
• 通讯作者: Maragos,WilliamF

Inflammation and age-related iron accumulation in F344 rats.

• DOI: 10.2174/1874609810801020112
• 发表时间: 2008-06
• 期刊: Current aging science
• 作者: Randy L. Hunter;Mei Liu;D. Choi;W. Cass;G. Bing

Involvement of cytokines in human immunodeficiency virus-1 protein Tat and methamphetamine interactions in the striatum.

细胞因子参与人类免疫缺陷病毒 1 蛋白 Tat 和纹状体中甲基苯丙胺的相互作用。

• DOI: 10.1016/j.expneurol.2006.01.009
• 发表时间: 2006
• 期刊: Experimental neurology.
• 作者: Theodore,Shaji;Cass,WayneA;Maragos,WilliamF
• 通讯作者: Maragos,WilliamF

Inhibition of tumor necrosis factor-alpha signaling prevents human immunodeficiency virus-1 protein Tat and methamphetamine interaction.

抑制肿瘤坏死因子-α 信号传导可防止人类免疫缺陷病毒 1 蛋白 Tat 与甲基苯丙胺相互作用。

• DOI: 10.1016/j.nbd.2006.05.005
• 发表时间: 2006
• 期刊: Neurobiology of disease
• 影响因子: 6.1
• 作者: Theodore,Shaji;Cass,WayneA;Nath,Avindra;Steiner,Joseph;Young,Kristie;Maragos,WilliamF
• 通讯作者: Maragos,WilliamF

Intrastriatal lipopolysaccharide injection induces parkinsonism in C57/B6 mice.

• DOI: 10.1002/jnr.22012
• 发表时间: 2009-06
• 期刊: JOURNAL OF NEUROSCIENCE RESEARCH
• 影响因子: 4.2
• 作者: Hunter, Randy L.;Cheng, Baohua;Choi, Dong-Young;Liu, Mei;Liu, Shuwei;Cass, Wayne A.;Bing, Guoying
• 通讯作者: Bing, Guoying