Mitochondrial Complex Inhibitors Preferentially Damage Substantia Nigra Dopamine Neurons in Rat Brain Slices

Bywood, Petra Teresia; Johnson, Stephen M.

doi:10.1006/exnr.2002.8044

Cited by 45 publications

(18 citation statements)

References 50 publications

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“…Furthermore, Milusheva and coworkers (2003) showed that oxidative stress can lead to a flood of non-synaptic noradrenaline from cytoplasmic stores, which consequently provides an additional source of highly reactive free radicals if combined with mitochondrial dysfunction (caused by rotenone) and thus initiating a fatal self-amplifying cycle leading to neuronal degeneration. However, in in vitro studies, it has been shown that rotenone preferentially kills dopaminergic neurons in the SN, whereas noncatechominergic neurons, such as those in the perifornical nucleus, were more resistant to rotenone toxicity (Bywood & Johnson, 2003). In addition to these effects on PD related areas of the BG, we found that specifically the dopaminergic amacrine cells of the retina are degenerating as a result of the chronic rotenone application.…”

Section: The Density Of Retinal Da-ergic Cells Is Decreased In Rotenomentioning

confidence: 59%

A rat model of Parkinsonism shows depletion of dopamine in the retina

Biehlmaier

Alam

Schmidt

2007

Neurochemistry International

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A rat model of Parkinsonism shows depletion of dopamine in the retina AbstractThe retinal dopamine (DA) deficiency is an important feature of the pathogenesis in Parkinson's disease (PD) visual dysfunction. Systemic inhibition of complex I (rotenone) in rats has been proposed as a model of PD. In this study, we investigated whether systemic inhibition of complex I can induce impairment of DA-ergic cells in the retina, similar to the destruction of retinal cells found in PD patients. Rotenone (2.5mg/kg i.p., daily) was administered over 60 days. Neurochemically, rotenone treated rats showed a depletion of DA in the striatum and substantia nigra (SN). In addition, the number of retinal DA-ergic amacrine cells was significantly reduced in the rotenone treated animals. This study is the first one giving highlight towards a deeper understanding of systemic complex I inhibition (rotenone as an environmental toxin) and the connection between both, DA-ergic degeneration in the nigrostriatal pathway, and in the DA-ergic amacrine cells of the retina.Retinal degeneration in a rotenone PD model This study is the first one giving highlight towards a deeper understanding of systemic complex I inhibition (rotenone as an environmental toxin) and the connection between both, DA-ergic degeneration in the nigrostriatal pathway, and in the DA-ergic amacrine cells of the retina.

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Section: The Density Of Retinal Da-ergic Cells Is Decreased In Rotenomentioning

confidence: 59%

A rat model of Parkinsonism shows depletion of dopamine in the retina

Biehlmaier

Alam

Schmidt

2007

Neurochemistry International

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“…Similarly, mitochondrial dysfunction (e.g. uncoupling of mitochondrial complexes I and III; (Bywood & Johnson 2003) has been indicated as an important pathway in the pathophysiology of PD. However, it is debatable whether the high oxidative burden and mitochondrial function are causative factors since these are not specific for dopaminergic neurons in SN pc .…”

Section: Proposed Mechanisms Of Pesticide-induced Pdmentioning

confidence: 99%

In vitrodopaminergic neurotoxicity of pesticides: a link with neurodegeneration?

Heusinkveld

Berg

Westerink

2014

Veterinary Quarterly

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“…Animal models of PD which employed complex I inhibitors such as MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) or rotenone [47] also reveal the differential vulnerability of complex I. This deficiency of complex I activity may reasonably be attributed to the mtDNA depletion as an increase in deleted mtDNA occurs in the striatum in PD and in senescence [48].…”

Section: Mitochondrial Dna Depletion Altered the Expression Of Mnsod mentioning

confidence: 99%

Metabolic and Antioxidant System Alterations in an Astrocytoma Cell Line Challenged with Mitochondrial DNA Deletion

2007

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Oxidative stress can induce mitochondrial dysfunction, mitochondrial DNA (mtDNA) depletion, and neurodegeneration, although the underlying mechanisms are poorly understood. The major mitochondrial antioxidant system that protects cells consists of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx) and glutathione (GSH). To investigate the putative adaptive changes in antioxidant enzyme protein expression and targeting to mitochondria as mtDNA depletion occurs, we progressively depleted U87 astrocytoma cells of mtDNA by chronic treatment with ethidium bromide (EB, 50 ng/ml). Cellular MnSOD protein expression was markedly increased in a time-related manner while that of GPx showed time-related decreases. The mtDNA depletion also altered targeting or subcellular distribution of GPx, suggesting the importance of intact mtDNA in mitochondrial genome-nuclear genome signaling/communication. Cellular NADP(+)-ICDH activity also showed marked, time-related increases while their GSH content decreased. Thus, our findings suggest that interventions to elevate MnSOD, GPx, NADP(+)-ICDH, and GSH levels may protect brain cells from oxidative stress.

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Mitochondrial Complex Inhibitors Preferentially Damage Substantia Nigra Dopamine Neurons in Rat Brain Slices

Cited by 45 publications

References 50 publications

A rat model of Parkinsonism shows depletion of dopamine in the retina

A rat model of Parkinsonism shows depletion of dopamine in the retina

In vitrodopaminergic neurotoxicity of pesticides: a link with neurodegeneration?

Metabolic and Antioxidant System Alterations in an Astrocytoma Cell Line Challenged with Mitochondrial DNA Deletion

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