Neuronal nitric oxide synthase inhibition attenuates the development of L-DOPA-induced dyskinesia in hemi-Parkinsonian rats

Takuma, Kazuhiro; Tanaka, Teruhisa; Takahashi, Tsuyoshi; Hiramatsu, Naoki; Ota, Yuki; Ago, Yukio; Matsuda, Takehisa

doi:10.1016/j.ejphar.2012.03.008

Cited by 31 publications

(29 citation statements)

References 38 publications

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“…In addition, other data have shown the potential role of GABAergic striatal interneurons expressing somatostatin, neuropeptide Y, NADPH diaphorase and NOS in compensation for dopamine loss in experimental or idiopathic PD (Ibáñez-Sandoval et al, 2010). Recent results have demonstrated that nNOS inhibition attenuates the development of L-DOPA-induced dyskinesia in hemi-parkinsonian rats (Takuma et al, 2012), thus confirming the pathogenic effects of nNOS. Moreover, new findings have provided further evidence of an anti-dyskinetic effect of NOS inhibitors.…”

Section: Neurotoxicitymentioning

confidence: 60%

Why is nitric oxide important for our brain?

Džoljić¹,

Grbatinić²,

Kostić³

2015

Functional Neurology

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SummaryThe freely diffusible gaseous compound nitric oxide (NO) has been shown to be an important messenger in many organ systems throughout the body, and particularly in the central nervous system (CNS). The importance of NO as an intermediary in cell communication in the brain is highlighted by the fact that the excitatory amino acid glutamate, the most abundant CNS neurotransmitter, is an initiator of the reaction that forms NO. Because of its numerous physiological and pathophysiological roles, the impact of NO on clinical medicine is developing. NO can act as a "double-edged sword" and it has been demonstrated that clarification of the dual effect of NO might have implications for clinical medicine, and could lead to the emergence of therapeutic opportunities. Accordingly, NO was proclaimed "Mole cule of the Year" in 1992 by the journal Science, while discovery of the pathways and roles of NO was acknowledged with the Nobel Prize in 1998. Additionally, the ubiquity of NO in the CNS implies that drugs designed to modify the biological activity of NO may have distinct effects. Thus, further clinical applications of NO, of its analogs or of newly developed NOS inhibitors are forthcoming. The therapeutic challenge would be to succeed in manipulating the NO pathways selectively.

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Section: Neurotoxicitymentioning

confidence: 60%

Why is nitric oxide important for our brain?

Džoljić¹,

Grbatinić²,

Kostić³

2015

Functional Neurology

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“…Cyclin-dependent kinase 5 (Cdk5) has been implicated in the pathogenesis of LIDs, which is known to increase the expression of Cdk5 receptor [140]. To this effect, the Cdk5 inhibitor roscovitine has been tested in 6-OHDA-lesioned rat model for its efficacy against LIDs and found that roscovotine can reduce the apomorphine-induced rotations in PD rats, but fails to decrease LIDs [141].…”

Section: Cyclin-dependent Kinase 5 Antagonistsmentioning

confidence: 99%

“…Using unilateral 6-OHDA lesioned rats to examine the effect of nitric oxide synthase (NOS) inhibitors in preventing LIDs, the nonselective NOS inhibitor, N(G)-nitro-l-arginine methyl ester, and nNOS inhibitor 7-nitroindazole have been found to ameliorate the development of LIDs, but the inducible NOS inhibitor aminoguanidine does not show such effect [140].…”

Section: Nitric Oxide Synthase Inhibitorsmentioning

confidence: 99%

“…Modulation of DA, glutamate,adenosine, and other systems has been explored in various animal models of LIDs [129][130][131][132][133][134][135][136][137][138][139][140][141][142][143][144][145].…”

Section: Therapeutic Strategies For Lids In Animal Models Of Pdmentioning

confidence: 99%

“…Daily use of levodopa manifests some changes in signaling molecules, including ΔFosB, phospho-DARPP32, and phosoho-GluA1AMPA receptor subunits, and also increases nitric oxide production in the striatum [140]. Using unilateral 6-OHDA lesioned rats to examine the effect of nitric oxide synthase (NOS) inhibitors in preventing LIDs, the nonselective NOS inhibitor, N(G)-nitro-l-arginine methyl ester, and nNOS inhibitor 7-nitroindazole have been found to ameliorate the development of LIDs, but the inducible NOS inhibitor aminoguanidine does not show such effect [140].…”

Section: Nitric Oxide Synthase Inhibitorsmentioning

confidence: 99%

See 2 more Smart Citations

Animal Models of Parkinson's Disease: A Gateway to Therapeutics?

Sayana

Jankovic

2014

Neurotherapeutics

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Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.

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l-DOPA-induced dyskinesia in Parkinson's disease: Are neuroinflammation and astrocytes key elements?

Del‐Bel

Bortolanza

Pereira

et al. 2016

Synapse

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Inflammation in Parkinson's disease (PD) is a new concept that has gained ground due to the potential of mitigating dopaminergic neuron death by decreasing inflammation. The solution to this question is likely to be complex. We propose here that the significance of inflammation in PD may go beyond the nigral cell death. The pathological process that underlies PD requires years to reach its full extent. A growing body of evidence has been accumulated on the presence of multiple inflammatory signs in the brain of PD patients even in very late stages of the disease. Because neuron-microglia-astrocyte interactions play a major role in the plasticity of neuronal response to l-DOPA in post-synaptic neurons, we focused this review on our recent results of l-DOPA-induced dyskinesia in rodents correlating it to significant findings regarding glial cells and neuroinflammation. We showed that in the rat model of PD/l-DOPA-induced dyskinesia there was an increased expression of inflammatory markers, such as the enzymes COX2 in neurons and iNOS in glial cells, in the dopamine-denervated striatum. The gliosis commonly seem in PD was associated with modifications in astrocytes and microglia that occur after chronic treatment with l-DOPA. Either as a cause, consequence, or promoter of progression of neuronal degeneration, inflammation plays a role in PD. The key aims of current PD research ought to be to elucidate (a) the time sequence in which the inflammatory factors act in PD patient brain and (b) the mechanisms by which neuroinflammatory response contributes to the collateral effects of l-DOPA treatment.

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Neuronal nitric oxide synthase inhibition attenuates the development of L-DOPA-induced dyskinesia in hemi-Parkinsonian rats

Cited by 31 publications

References 38 publications

Why is nitric oxide important for our brain?

Why is nitric oxide important for our brain?

Animal Models of Parkinson's Disease: A Gateway to Therapeutics?

l-DOPA-induced dyskinesia in Parkinson's disease: Are neuroinflammation and astrocytes key elements?

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