Abstract:
:The development of reliable biological markers of nigrostriatal degeneration has important implications from both experimental and clinical viewpoints, since such biomarkers could be used for diagnostic and monitoring purposes in models of parkinsonism as well as in Parkinson's disease patients. In this study, levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in the cerebrospinal fluid (CSF) of normal and parkinsonian squirrel monkeys in order to assess their reliability as indicators of nigrostriatal injury. In particular, we tested the hypothesis that these measurements may become more accurate by inhibiting catecholamine-O-methyltransferase (COMT) activity and therefore blocking the conversion of DOPAC to homovanillic acid. Oral administration of the COMT inhibitor tolcapone (2 doses of 15 mg/kg each with a 4-h interval) significantly reduced enzyme activity in the monkey brain. Tolcapone treatment enhanced CSF DOPAC concentrations in unlesioned animals (by approximately four times) as well as monkeys rendered parkinsonian after severe nigrostriatal dopaminergic injury caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Importantly, however, COMT inhibition greatly magnified the differences in CSF DOPAC levels between control and parkinsonian monkeys, since MPTP-induced DOPAC depletion was 35% in the absence vs >60% in the presence of tolcapone. Thus, tolcapone administration enhances the detection of DOPAC in the CSF and, by doing so, improves the reliability of CSF DOPAC as a marker of nigrostriatal degeneration.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Thiffault C,Langston JW,Di Monte DAdoi
10.1016/s0014-4886(03)00140-7keywords:
subject
Has Abstractpub_date
2003-09-01 00:00:00pages
173-9issue
1eissn
0014-4886issn
1090-2430pii
S0014488603001407journal_volume
183pub_type
杂志文章abstract::Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns. GMH causes neurological sequelae such as cerebral palsy, post-hemorrhagic hydrocephalus, and mental retardation. Despite this, there is no standardized animal model of spontaneous GMH using newborn rats to depict the condit...
journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
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更新日期:1984-08-01 00:00:00
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journal_title:Experimental neurology
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1996.0060
更新日期:1996-04-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1998.6948
更新日期:1998-12-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2003.08.018
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
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journal_title:Experimental neurology
pub_type: 杂志文章,评审
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更新日期:2014-08-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2003.09.007
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(84)90192-4
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.10.020
更新日期:2012-01-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2011.05.005
更新日期:2011-08-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(85)90044-5
更新日期:1985-10-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.1996.0070
更新日期:1996-04-01 00:00:00
abstract::Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disorder. AD is mostly a sporadic disorder and its main risk factor is age, but mutations in three genes that promote the accumulation of the amyloid-β (Aβ42) peptide revealed the critical role of amyloid precursor protein ...
journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2015.05.013
更新日期:2015-12-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章,评审
doi:10.1016/j.expneurol.2007.09.002
更新日期:2008-02-01 00:00:00
abstract::The age-dependent effects of sympathetic superior cervical ganglionectomy on smooth muscle alpha-adrenoceptor contractile responses were investigated in Müller's muscle in the superior eyelid of the Sprague-Dawley rat. Ganglionectomies in juvenile (32 days) and adult (70 days) rats produced sustained sympathetic dener...
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pub_type: 杂志文章
doi:10.1016/0014-4886(86)90031-2
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2002.7863
更新日期:2002-04-01 00:00:00
abstract::The effect of proximal nerve crush on regeneration after unrepaired nerve transection was studied in feline cutaneous nerves. Delays between the initial transection and the subsequent nerve crush varied between 0 (immediate crush) and 13 months. A survival time of 6 to 12 months after the crush was allowed for regener...
journal_title:Experimental neurology
pub_type: 杂志文章
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abstract::Little is known about the morphological effects of alcoholism on the developing adolescent brain and its consequences into adulthood. We studied here the relationship between two neurotransmitter systems (the serotoninergic and nitrergic) and the astrocytic and neuronal cytoskeleton immediately and long after drinking...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2006.03.001
更新日期:2006-08-01 00:00:00
abstract::Nerve growth factor (NGF) enhances neuronal survival during injury to the mature central and peripheral nervous systems, but its potential as a neuroprotective factor in the enteric nervous system (ENS) has not been examined. We used the trinitrobenzene sulfonic acid (TNBS)-induced model of colitis to examine if NGF-s...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2004.10.003
更新日期:2005-02-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(86)90255-4
更新日期:1986-12-01 00:00:00
abstract::Discovery of new central nervous system (CNS) acting therapeutics has been slowed down by the lack of useful applicable biomarkers of disease or drug action often due to inaccessibility of relevant human CNS tissue and cell types. In recent years, non-neuronal cells, such as astrocytes, have been reported to play a hi...
journal_title:Experimental neurology
pub_type: 临床试验,杂志文章
doi:10.1016/j.expneurol.2011.09.002
更新日期:2011-12-01 00:00:00
abstract::The longitudinal distributions of both phrenic and medial gastrocnemius motoneurons were quantitatively studied in the cat spinal cord. Both populations of motoneurons were retrogradely labeled by applying horseradish peroxidase (HRP) to the cut central ends of the appropriate peripheral nerves. The longitudinal posit...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/0014-4886(84)90089-x
更新日期:1984-12-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2000.7451
更新日期:2000-09-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2015.06.023
更新日期:2015-09-01 00:00:00
abstract::The distribution and relative intrafascicular contribution of myelin fibers derived from spinal segments L-4 to L-6 were analyzed in adult rat sciatic nerve and its main branches, using 200-kDa neurofilament subunit immunodetection in previously injured nerve sections in the L-4 or L-5 spinal branch or both. These bra...
journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1006/exnr.2001.7806
更新日期:2002-02-01 00:00:00