Systemic administration of antioxidants does not protect mice against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)

Martinovits, Giora; Melamed, Eldad; Cohen, Oren S.; Rosenthal, J; Uzzan, Anat

doi:10.1016/0304-3940(86)90602-6

Cited by 71 publications

(28 citation statements)

References 21 publications

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“…The possible protective effect of pretreatment with vitamin E in experimental models of parkinsonism induced by MPTP or 6-hydroxydopamine is not proven (Baldessarini et al, 1986;Cadet et al, 1989;Martinovits et al, 1986;Perry et al, 1985Perry et al, , 1987Yong et al, 1986), although vitamin E deficiency in mice does increase the susceptibility to MPTP-induced neurotoxicity in the substantia nigra (Adams et al, 1990;Odunze et al, 1990). In addition, possitron emission tomography studies with lSF-dopa have shown subclinical nigrostriatal damage in patients with chronic deficiency of vitamin E (Dexter et al, 1994).…”

Section: Discussionmentioning

confidence: 95%

Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Parkinson's disease

Molina

Bustos

Jiménez‐Jiménez

et al. 1997

J. Neural Transmission

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We compared CSF and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 34 patients with Parkinson's disease (PD) and 47 controls. CSF and serum vitamin E levels were correlate. The mean CSF and serum vitamin E levels, and the CSF/serum ratio of PD patients did not differ significantly between the groups. There was no influence of antiparkinsonian therapy on CSF vitamin E levels. CSF vitamin E levels did not correlate with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. These results suggest that CSF vitamin E concentrations are unrelated with the risk for PD.

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Section: Discussionmentioning

confidence: 95%

Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Parkinson's disease

Molina

Bustos

Jiménez‐Jiménez

et al. 1997

J. Neural Transmission

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“…that MPTP lowers glutathione in dopamine neurons, or that glutathione and antioxidants protect from the neurotoxicity of MPTP. These reports could not be confirmed in subsequent studies [35,36]. Perhaps the most decisive evidence against the oxidative stress hypothesis has come from the demonstration [37] that anti-oxidants do not protect dopamine neurons in culture from MPP ÷…”

Section: The Oxidative Stress Hypothesismentioning

confidence: 94%

Mechanism of the neurotoxicity of MPTP

1990

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This review summarizes advances in our understanding of the biochemical events which underlie the remarkable neurotoxic action of MPTP (1-methyl-4-phenyl-l-l,2,3,6-tetrahydropyridine) and the parkinsonian symptoms it causes in primates. The initial biochemical event is a two-step oxidation by monoamine oxidase B in glial cells to MPP + (1-methyl-4-phenylpyridinium). A large number of MPTP analogs substituted in the aromatic (but not in the pyridine) ring are also oxidized by monoamine oxidase A or B, is in some cases faster than any previously recognized substrate. Alkyl substitution at the Z-position changes MPTP, a predominantly B type substrate, to an A substrate. Following concentration in the dopamine neurons by the synaptic system, which has a high affinity for the carrier, MPP + and its positively charged neurotoxic analogs are further concentrated by the electrical gradient of the inner membrane and then more slowly penetrate the hydrophobic reaction site on NADH dehydrogenase. Both of the latter events are accelerated by the tetraphenylboron anion, which forms ion pairs with MPP + and its analogs. Mitochondrial damage is now widely accepted as the primary cause of the MPTP induced death of the nigrostriatal cells. The molecular target of MPP ÷, its neurotoxic product, is NADH dehydrogenase. Recent experiments suggest that the binding site is at or near the combining site of the classical respiratory inhibitors, rotenone and piericidin A.Monoamine oxidase; MPTP (l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine); Neurotoxin; NADH dehydrogenase

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“…Demyelination was induced unilaterally by direct single injection of 3 ll of 0.01% ethidium bromide in sterile 0.9% saline (Sim et al 2000) at the rate of 1 ll/min into the right dentate gyrus of hippocampal formation, using appropriate stereotaxic coordinates (AP = -2.8; ML = ?1.8; DV = ?2.5) (Paxinos and Watson 2006). Animals in experimental groups received 100 mg/kg vitamin E (DSM Nutritional Products, Village-Neuf, France) (Martinovits et al 1986;Offen et al 2001;Cinthia et al 2009) or 5 lg/kg vitamin D3 (DSM Nutritional Products, Village-Neuf, France) (Garcion et al 2003) for 2, 7, or 28 days post lesion. Soybean oil (Hayes et al 2004) as the vehicle of vitamins E and D3 was used as control.…”

Section: Gliotoxin Injection and Treatmentsmentioning

confidence: 99%

Vitamins E and D3 Attenuate Demyelination and Potentiate Remyelination Processes of Hippocampal Formation of Rats Following Local Injection of Ethidium Bromide

et al. 2009

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Cognitive deficits have been observed in patients with multiple sclerosis (MS) due to hippocampal insults. Antioxidant vitamins D and E are suggested for patients suffering from neurodegenerative diseases like MS, while their mechanisms of action are not well understood. Here, we have tried to study the effects of these vitamins on demyelination, cell death, and remyelination of rat hippocampus following local ethidium bromide (EB) injection. Animals received 100 mg/kg vitamin E or 5 microg/kg of vitamin D3 for 2, 7, or 28 days. The extent of demyelination, myelin staining intensity, and expression of myelin basic protein and caspase-3 were investigated using histological and immunoblotting verification. Administration of EB alone caused demyelination, cell death, and afterward an endogenous repair. Vitamins E and D3 reduced the EB-induced damage and increased the endogenous remyelination of hippocampus. Although the anti-apoptotic effect of these vitamins and protection against demyelination were predictable based on their antioxidant effect, our results indicated the positive effect of vitamins E and D3 on process of remyelination by endogenous progenitor cells and supported their possible therapeutic effects in the context of demyelinating diseases like MS.

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Systemic administration of antioxidants does not protect mice against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)

Cited by 71 publications

References 21 publications

Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Parkinson's disease

Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Parkinson's disease

Mechanism of the neurotoxicity of MPTP

Vitamins E and D3 Attenuate Demyelination and Potentiate Remyelination Processes of Hippocampal Formation of Rats Following Local Injection of Ethidium Bromide

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