DOPAMINE NERVES SUPRESS HYDROXYL RADICAL FORMATION IN NE

多巴胺神经抑制 NE 中羟基自由基的形成

• 批准号: 6024167
• 负责人: RICHARD M KOSTRZEWA
• 金额: $ 8.98万
• 依托单位: EAST TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-10 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6024167
• 关键词: 6 hydroxydopamine; Parkinson's disease; antioxidants; autooxidation; dihydroxyphenylalanine; dopamine; experimental brain lesion; hydroxyl radical; laboratory rat; microdialysis; neuropathology; neuroprotectants; neurotoxins; newborn animals; occipital lobe /cortex; pathologic process; quinones; salicylate; substantia nigra; tyrosine analog

DESCRIPTION: (Verbatim from the Applicant's Abstract) Dopamine (DA) is the catecholamine most easily auto-oxidized to reactive o-quinones and is most involved in generation of other reactive oxygen species (ROS), of which hydroxyl radical (OH) is the most reactive. It is for this reason that DA is suspect as an autotoxin, over time, destroys DA nerves, including substantia nigra pars compacta, resulting in Parkinson's disease. Counter to this view of DA as an autotoxin, they found that basal OH in neostriatum was low when DA innervation of neostriatum was intact, but that OH increased several fold if DA innervation suppresses OH generation in the neostriatum. Various degrees of DA-denervation of neostriatum (15-99%) first will be produced by giving 6-hydroxydopamine to neonatal rats. In adulthood an in vivo microdialysis probe will be implanted, with the probe tip residing in neostriatum; and salicylate will be included in microdialysates as a spin trap for OH, detected with HPLC/EC as 2,5-dihydroxybenzoic acid and 2,3-DHBA. To eliminate other ontogenetic processes as factors associated with increased OH formation in DA-denervated rats, the neostriatum of one group of rats will be unilaterally denervated at 8-10 wk by 7-OHDA injected into Snpc. To test that DA per se is involved, a group of rats will be DA depleted with a-methyl-p-tyrosine. Other experiments to test the role of DA primarily as an anti-oxidant include 1) effect of subchronic L-DOPA treatment on OH; 2) direct inhibition of OH formation by DA microdialysates; 3) mediation of OH generation by glutamic acid in DA-denervated neostriatum. Microdialysates (extraneuronal compartment) and whole striatum (mainly intraneuronal compartment) will be analyzed in all studies, to assess DA effects in each compartment and verify completeness of DA-denervation. Findings should validate or refute the hypothesis that DA innervation is primarily neuroprotectant and suppressive of OH in neostriatum.

描述：（逐字摘自申请人摘要）多巴胺（DA）是

项目成果

Amphetamine-induced enhancement of neostriatal in vivo microdialysate dopamine content in rats, quinpirole-primed as neonates.

安非他明诱导大鼠新生纹状体体内微透析液多巴胺含量的增加，并在新生儿时给予喹吡罗。

• 发表时间: 2001
• 期刊: Polish journal of pharmacology.
• 作者: Nowak,P;Brus,R;Kostrzewa,RM
• 通讯作者: Kostrzewa,RM

Ontogenetic quinpirole treatments fail to prime for D2 agonist-enhancement of locomotor activity in 6-hydroxydopamine-lesioned rats.

个体发生喹吡罗治疗未能引发 D2 激动剂增强 6-羟基多巴胺损伤大鼠的运动活性。

• DOI: 10.1007/bf03033153
• 发表时间: 2003
• 期刊: Neurotoxicity research
• 影响因子: 3.7
• 作者: Brus,Ryszard;Kostrzewa,RichardM;Nowak,Przemysław;Perry,KenW;Kostrzewa,JohnP
• 通讯作者: Kostrzewa,JohnP

Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review.

• DOI: 10.1007/bf03033166
• 发表时间: 2003-01-01
• 期刊: NEUROTOXICITY RESEARCH
• 影响因子: 3.7
• 作者: Kostrzewa, RM;Segura-Aguilar, J
• 通讯作者: Segura-Aguilar, J

Proposed animal model of severe Parkinson's disease: neonatal 6-hydroxydopamine lesion of dopaminergic innervation of striatum.

拟议的严重帕金森病动物模型：纹状体多巴胺能神经支配的新生儿 6-羟基多巴胺损伤。

• DOI: 10.1007/978-3-211-45295-0_43
• 发表时间: 2006
• 期刊: Journal of neural transmission. Supplementum
• 作者: Kostrzewa,RM;Kostrzewa,JP;Brus,R;Kostrzewa,RA;Nowak,P
• 通讯作者: Nowak,P

Amino acids in neurobiology: neuroprotective and neurotoxic aspects of amino acids involved in neurotransmission and neuromodulation -- general introduction.

神经生物学中的氨基酸：参与神经传递和神经调节的氨基酸的神经保护和神经毒性方面——一般介绍。

• DOI: 10.1007/s007260200027
• 发表时间: 2002
• 期刊: Amino acids
• 影响因子: 3.5
• 作者: Kretschmer,BD;Schmidt,WJ;Kostrzewa,RM;Marschitz-Herra,M
• 通讯作者: Marschitz-Herra,M