Effect of l-DOPA on nitric oxide production in striatum of freely mobile mice

Itokawa, Kaori; Ohkuma, Aya; Araki, Nobuhito; Tamura, Naotoshi; Shiota, Kunio

doi:10.1016/j.neulet.2006.03.064

Cited by 17 publications

(5 citation statements)

References 7 publications

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“…Hitherto, the study of NO in the effects of L-DOPA has produced conflicting results. Despite the fact that early evidence failed to reveal any L-DOPA-modulation of striatal NO levels [190,191], a recent microdialysis study showed increased production of NO 3 although with no changes in either NO 3 or total NO in mice striatum after L-DOPA administration [192].…”

Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 97%

Nitric Oxide Modulation of the Basal Ganglia Circuitry: Therapeutic Implication for Parkinson's Disease and Other Motor Disorders

Pierucci

Galati

Valentino

et al. 2011

CNSNDDT

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Several recent studies have emphasized a crucial role for the nitrergic system in movement control and the pathophysiology of the basal ganglia (BG). These observations are supported by anatomical evidence demonstrating the presence of nitric oxide synthase (NOS) in all the basal ganglia nuclei. In fact, nitrergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high expression of nitric oxide (NO)-producing neurons, with the striatum having the greatest number, together with important NO afferent input. In this paper, the distribution of NO in the BG nuclei will be described. Furthermore, evidence demonstrating the nitrergic control of BG activity will be reviewed. The new avenues that the increasing knowledge of NO in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. For example, inhibition of striatal NO/guanosine monophosphate signal pathway by phosphodiesterases seems to be effective in levodopa-induced dyskinesia. However, the results of experimental studies have to be interpreted with caution given the complexities of nitrergic signalling and the limitations of animal models. Nevertheless, the NO system represents a promising pharmacological intervention for treating Parkinson's disease and related disorders.

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Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 97%

Nitric Oxide Modulation of the Basal Ganglia Circuitry: Therapeutic Implication for Parkinson's Disease and Other Motor Disorders

Pierucci

Galati

Valentino

et al. 2011

CNSNDDT

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“…Brain infusion or i.p. injection of the drug increased the levels of OH À and NO in substantia nigra and the striatum (Golembiowska et al, 2008;Itokawa et al, 2006;Smith et al, 1994;but see Camp et al, 2000), and potentiated neurotoxic effects caused by exogenous 6-OHDA (Naudin et al, 1995). Treatment with L-DOPA for 7-28 days also increased the endogenous production of 6-OHDA in the striatum (Maharaj et al, 2005).…”

Section: Animal Studiesmentioning

confidence: 99%

l-DOPA: A scapegoat for accelerated neurodegeneration in Parkinson's disease?

Lipski

Nisticò

Berretta

et al. 2011

Progress in Neurobiology

103

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“…Pre-clinical in vivo studies have shown that L-DOPA can damage dopaminergic neurons due to oxidative stress and perhaps through other mechanisms [8, 9]. Studies have shown that direct intraniagral infusion of L-DOPA in rats results in reduced dopaminergic neuron numbers [10] whilst other studies have demonstrated that L-DOPA increases the levels of nitric oxide in the substantia nigra and striatum [11, 12]. In contrast, many in vitro studies have shown that L-DOPA may be neuroprotective through decreased lipid peroxidation [13, 14].…”

Section: Introductionmentioning

confidence: 99%

Proteome analysis reveals roles of L-DOPA in response to oxidative stress in neurons

et al. 2014

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BackgroundParkinson’s disease (PD) is the second most common neurodegenerative movement disorder, caused by preferential dopaminergic neuronal cell death in the substantia nigra, a process also influenced by oxidative stress. L-3,4-dihydroxyphenylalanine (L-DOPA) represents the main treatment route for motor symptoms associated with PD however, its exact mode of action remains unclear. A spectrum of conflicting data suggests that L-DOPA may damage dopaminergic neurons due to oxidative stress whilst other data suggest that L-DOPA itself may induce low levels of oxidative stress, which in turn stimulates endogenous antioxidant mechanisms and neuroprotection.ResultsIn this study we performed a two-dimensional gel electrophoresis (2DE)-based proteomic study to gain further insight into the mechanism by which L-DOPA can influence the toxic effects of H2O2 in neuronal cells. We observed that oxidative stress affects metabolic pathways as well as cytoskeletal integrity and that neuronal cells respond to oxidative conditions by enhancing numerous survival pathways. Our study underlines the complex nature of L-DOPA in PD and sheds light on the interplay between oxidative stress and L-DOPA.ConclusionsOxidative stress changes neuronal metabolic routes and affects cytoskeletal integrity. Further, L-DOPA appears to reverse some H2O2-mediated effects evident at both the proteome and cellular level.

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Effect of l-DOPA on nitric oxide production in striatum of freely mobile mice

Cited by 17 publications

References 7 publications

Nitric Oxide Modulation of the Basal Ganglia Circuitry: Therapeutic Implication for Parkinson's Disease and Other Motor Disorders

Nitric Oxide Modulation of the Basal Ganglia Circuitry: Therapeutic Implication for Parkinson's Disease and Other Motor Disorders

l-DOPA: A scapegoat for accelerated neurodegeneration in Parkinson's disease?

Proteome analysis reveals roles of L-DOPA in response to oxidative stress in neurons

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