In vivo trapping of hydroxyl free radicals in the striatum utilizing intracranial microdialysis perfusion of salicylate: effects of MPTP, MPDP+, and MPP+

Obata, Toshio; Chiueh, Chuang C.

doi:10.1007/bf01245361

Cited by 108 publications

(42 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several of these compounds can also inhibit Complex I, further affecting energy impairment (67). Although the present studies have emphasized the role of intracellular DA in neurotoxicity, in vivo studies have established that MPP ϩ -mediated efflux of DA also generates extracellular hydroxyl radicals (17). Indeed, DA can be toxic both in vitro (31,73) and in vivo (74,75).…”

Section: Role Of Dopamine In Mppmentioning

confidence: 82%

“…However, MPP ϩ does affect other processes. For example, MPP ϩ rapidly induces DA release and subsequent formation of hydroxyl radicals both in vivo and in vitro (12)(13)(14)(15)(16)(17). Because the timing of this process is comparable with exocytosis (18), the deleterious effects of extracellular DA oxidation may actually precede mitochondrial dysfunction, which occurs more slowly (6,19).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Parkinsonism-inducing Drug 1-Methyl-4-phenylpyridinium Triggers Intracellular Dopamine Oxidation

Lotharius

O’Malley

2000

Journal of Biological Chemistry

292

179

View full text Add to dashboard Cite

Section: Role Of Dopamine In Mppmentioning

confidence: 82%

mentioning

confidence: 99%

The Parkinsonism-inducing Drug 1-Methyl-4-phenylpyridinium Triggers Intracellular Dopamine Oxidation

Lotharius

O’Malley

2000

Journal of Biological Chemistry

292

179

View full text Add to dashboard Cite

“…Obata and Chiueh (1992) have used the technique of microdialysis to demonstrate in vivo that MPDP + (1-methyl-4-phenyl-2,3-dihydropyridinium ion, a further MPTP metabolite) as well as MPP + on intrastriatal application are briefly able to potentiate dopamine liberation from dopaminergic neurons in the rat, and indirectly that there was a brief production of hydroxyl free radicals, as evidenced by the reaction products formed with salicylic acid. In in vitro investigations using ESR (electron spin resonance) spectroscopy it could be shown that superoxide free radicals are formed during the metabolism of MPTP (e.g.…”

Section: The Mechanism Of the Neurotoxic Actionmentioning

confidence: 99%

Animal models of Parkinson's disease: An empirical comparison with the phenomenology of the disease in man

Gerlach

Riederer

1996

J. Neural Transmission

442

221

View full text Add to dashboard Cite

Animal models are an important aid in experimental medical science because they enable one to study the pathogenetic mechanisms and the therapeutic principles of treating the functional disturbances (symptoms) of human diseases. Once the causative mechanism is understood, animal models are also helpful in the development of therapeutic approaches exploiting this understanding. On the basis of experimental and clinical findings. Parkinson's disease (PD) became the first neurological disease to be treated palliatively by neurotransmitter replacement therapy. The pathological hallmark of PD is a specific degeneration of nigral and other pigmented brainstem nuclei, with a characteristic inclusion, the Lewy body, in remaining nerve cells. There is now a lot of evidence that degeneration of the dopaminergic nigral neurones and the resulting striatal dopamine-deficiency syndrome are responsible for its classic motor symptoms akinesia and bradykinesia. PD is one of many human diseases which do not appear to have spontaneously arisen in animals. The characteristic features of the disease can however be more or less faithfully imitated in animals through the administration of various neurotoxic agents and drugs disturbing the dopaminergic neurotransmission. The cause of chronic nigral cell death in PD and the underlying mechanisms remain elusive. The partial elucidation of the processes underlie the selective action of neurotoxic substances such as 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has however revealed possible molecular mechanisms that give rise to neuronal death. Accordingly, hypotheses concerning the mechanisms of these neurotoxines have been related to the pathogenesis of nigral cell death in PD. The present contribution starts out by describing some of the clinical, pathological and neurochemical phenomena of PD. The currently most important animal models (e.g. the reserpine model, neuroleptic-induced catalepsy, tremor models, experimentally-induced degeneration of nigrostriatal dopaminergic neurons with 6-OHDA, methamphetamine, MPTP, MPP+, tetrahydroisoquinolines, beta-carbolines, and iron) critically reviewed next, and are compared with the characteristic features of the disease in man.

show abstract

“…and MPP ϩ (3). MPTPinduced hydroxyl radical formation in the striatum and substantia nigra of the mouse has been shown in vivo (4); in addition, MPP ϩ alone promotes reactive oxygen species (ROS) formation (5)(6)(7).…”

Section: Parkinson's Disease (Pd)mentioning

confidence: 99%

The Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Induces Apoptosis in Mouse Nigrostriatal Glia

Serra

Sciola

Delogu

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Swiss mice were given 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 25 mg/kg/day, for 5 consecutive days and killed at different days after MPTP discontinuance. Decreases in striatal tyrosine hydroxylase activity and levels of dopamine and its metabolites were observed 1 day after MPTP discontinuance. Ascorbic acid and glutamate levels had increased, dehydroascorbic acid and GSH decreased, whereas catabolites of highenergy phosphates (inosine, hypoxanthine, xanthine, and uric acid) were unchanged. In addition, gliosis was observed in both striatum and substantia nigra compacta (SNc). Sections of SNc showed some terminal deoxynucleotidyl transferase-mediated 2-deoxyuridine 5-triphosphate nick end labeling (TUNEL)-positive cells. Neurochemical parameters of dopaminergic activity showed a trend toward recovery 3 days after MPTP discontinuance. At this time point, TUNEL-positive cells were detected in SNc; some of them showed nuclei with neuronal morphology. A late (days 6 -11) increase in striatal dopamine oxidative metabolism, ascorbic acid oxidative status, and catabolites of high-energy phosphates were observed concomitant with nigral neuron and nigrostriatal glial cell apoptotic death, as revealed by TUNEL, acridine orange, and Hoechst staining, and transmission electron microscopy. These data suggest that MPTP-induced activation/apoptotic death of glial cells plays a key role in the sequential linkage of neurochemical and cellular events leading to dopaminergic nigral neuron apoptotic death. Parkinson's disease (PD)1 is characterized by a selective loss of neurons in the substantia nigra compacta (SNc) and significant diminution of neostriatal content of dopamine and its major acidic metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Consequently, the functioning of the nigrostriatal dopaminergic system is impaired. Although cellular and molecular pathways leading to neuronal death in PD are still unknown, major biochemical processes such as oxidative stress and impaired energy metabolism are involved (for review, see Ref.

show abstract

In vivo trapping of hydroxyl free radicals in the striatum utilizing intracranial microdialysis perfusion of salicylate: effects of MPTP, MPDP+, and MPP+

Cited by 108 publications

References 27 publications

The Parkinsonism-inducing Drug 1-Methyl-4-phenylpyridinium Triggers Intracellular Dopamine Oxidation

The Parkinsonism-inducing Drug 1-Methyl-4-phenylpyridinium Triggers Intracellular Dopamine Oxidation

Animal models of Parkinson's disease: An empirical comparison with the phenomenology of the disease in man

The Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Induces Apoptosis in Mouse Nigrostriatal Glia

Contact Info

Product

Resources

About