Abstract:
:To define the molecular mechanisms underlying amphetamine (AMPH) neurotoxicity, primary cultures of dopaminergic neurons were examined for drug-induced changes in dopamine (DA) distribution, oxidative stress, protein damage, and cell death. As in earlier studies, AMPH rapidly redistributed vesicular DA to the cytoplasm, where it underwent outward transport through the DA transporter. DA was concurrently oxidized to produce a threefold increase in free radicals, as measured by the redox-sensitive dye dihydroethidium. Intracellular DA depletion using the DA synthesis inhibitor alpha-methyl-p-tyrosine or the vesicular monoamine transport blocker reserpine prevented drug-induced free radical formation. Despite these AMPH-induced changes, neither protein oxidation nor cell death was observed until 1 and 4 days, respectively. AMPH also induced an early burst of free radicals in a CNS-derived dopaminergic cell line. However, AMPH-mediated attenuation of ATP production and mitochondrial function was not observed in these cells until 48 to 72 hours. Thus, neither metabolic dysfunction nor loss of viability was a direct consequence of AMPH neurotoxicity. In contrast, when primary cultures of dopaminergic neurons were exposed to AMPH in the presence of subtoxic doses of the mitochondrial complex I inhibitor rotenone, cell death was dramatically increased, mimicking the effects of a known parkinsonism-inducing toxin. Thus, metabolic stress may predispose dopaminergic neurons to injury by free radical-promoting insults such as AMPH.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Lotharius J,O'Malley KLdoi
10.1002/1531-8249(200101)49:1<79::aid-ana11>3.0.cokeywords:
subject
Has Abstractpub_date
2001-01-01 00:00:00pages
79-89issue
1eissn
0364-5134issn
1531-8249journal_volume
49pub_type
杂志文章abstract::Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high-prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium-prevalence) and Sardinia (high-prevalence), we ascertained 216 pairs from 3...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20683
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:Huntington disease (HD) is an inherited neurodegenerative disease caused by the mutant huntingtin gene (mHTT), which harbors expanded CAG repeats. We previously reported that the brain vessel density is higher in mice and patients with HD than in controls. The present study determines whether vascular functio...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24428
更新日期:2015-08-01 00:00:00
abstract::Recently, the mutation causing early-onset generalized torsion dystonia has been identified as a GAG deletion in the gene for an adenosine triphosphate-binding protein named torsinA. We describe a German family with 5 clinically affected individuals carrying this mutation. In at least 4 of the 5 patients, the disease ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410440119
更新日期:1998-07-01 00:00:00
abstract::Three-dimensional (volume) magnetic resonance angiography is a noninvasive technique that images the intracranial and cervical arterial vasculature without contrast agents. Twenty-four children with strokes had combined parenchymal magnetic resonance imaging and magnetic resonance angiography 1 day to 4 years after ac...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410290603
更新日期:1991-06-01 00:00:00
abstract::Nineteen diabetic patients, 12 type I (insulin-dependent) and 7 type II (late-onset, non-insulin-dependent), underwent nocturnal polygraphic monitoring after a daytime medical evaluation that included tests of vagal responses and, in 6 patients, pulmonary function and hypercapnic and hypoxic responses. Five lean type ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410170415
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abstract::The pharmacokinetics of levodopa (L-dopa) in plasma and in cisternal and lumbar cerebrospinal fluid (CSF) were studied in Rhesus monkeys that were given 2- to 3-hour intravenous infusions of L-dopa. Steady-state L-dopa concentrations in cisternal CSF correlated well with plasma levels, and yielded a CSF:plasma ratio o...
journal_title:Annals of neurology
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doi:10.1002/ana.410270507
更新日期:1990-05-01 00:00:00
abstract::A recent controlled clinical trial suggested a role for amantadine as a treatment for pathological gambling in patients with Parkinson disease (PD). Analyzing data from a large cross-sectional study of impulse control disorders (ICDs) in PD, amantadine use (n = 728), vs no amantadine use (n = 2,357), was positively as...
journal_title:Annals of neurology
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doi:10.1002/ana.22164
更新日期:2010-12-01 00:00:00
abstract:OBJECTIVE:To evaluate the efficacy and safety of BHT-3009 in relapsing-remitting multiple sclerosis (MS) and to confirm that BHT-3009 causes immune tolerance. METHODS:BHT-3009 is a tolerizing DNA vaccine for MS, encoding full-length human myelin basic protein. Relapsing-remitting MS patients were randomized 1:1:1 into...
journal_title:Annals of neurology
pub_type: 杂志文章,随机对照试验
doi:10.1002/ana.21370
更新日期:2008-05-01 00:00:00
abstract::The reported inverse association between the S18Y variant of the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene and Parkinson's disease (PD) has strong biological plausibility. If confirmed, genetic association of this variant with PD may support molecular targeting of the UCHL1 gene and its product as a therape...
journal_title:Annals of neurology
pub_type: 杂志文章,meta分析
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更新日期:2004-04-01 00:00:00
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journal_title:Annals of neurology
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doi:10.1002/ana.410370306
更新日期:1995-03-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25167
更新日期:2018-03-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350716
更新日期:1994-01-01 00:00:00
abstract::The aim of this study was to evaluate the use of functional magnetic resonance imaging as an alternative to intraoperative electrocortical stimulation mapping for the localization of critical language areas in the temporoparietal region. We investigated several requirements that functional magnetic resonance imaging m...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10117
更新日期:2002-03-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20474
更新日期:2005-05-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.22669
更新日期:2012-04-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410340417
更新日期:1993-10-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20291
更新日期:2004-12-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10403
更新日期:2003-01-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150216
更新日期:1984-02-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
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更新日期:1996-03-01 00:00:00
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更新日期:2001-06-01 00:00:00
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journal_title:Annals of neurology
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更新日期:1993-02-01 00:00:00
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journal_title:Annals of neurology
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更新日期:1985-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/ana.10549
更新日期:2003-05-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
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更新日期:2010-12-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410280403
更新日期:1990-10-01 00:00:00
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journal_title:Annals of neurology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1997-06-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410100410
更新日期:1981-10-01 00:00:00
abstract::Three young adults with intractable complex partial seizures were studied by electroencephalography, magnetoencephalography, and electrocorticography. Interictal electroencephalographic (EEG) spikes for each patient were grouped according to their morphological characteristics and distribution across channels. Mapping...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410220311
更新日期:1987-09-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410250217
更新日期:1989-02-01 00:00:00