L-DOPA treatment from the viewpoint of neuroprotection

Ogawa, Norio; Asanuma, Masato; Miyazaki, Ikuko; Díaz-Corrales, Francisco J.; Miyoshi, Katsuhiko

doi:10.1007/s00415-005-4006-7

Cited by 27 publications

(11 citation statements)

References 102 publications

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“…It is well known that long-term treatment of levodopa in patients with PD causes various adverse side effects such as wearing-off phenomenon, dyskinesia, psychiatric symptom, and so on (Ahlskog and Munenter 2001;Ogawa et al 2005). Interestingly, a recent double-blind controlled study in Japan reported that an adjunctive treatment with zonisamide to levodopa can improve all the cardinal symptoms of PD (Murata 2004;Murata et al 2007).…”

Section: Discussionmentioning

confidence: 95%

A Novel Anti-Parkinsonian Agent, Zonisamide, Attenuates MPTP-Induced Neurotoxicity in Mice

et al. 2009

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Zonisamide, an anti-convulsant drug, has recently been shown to exert beneficial effects in Parkinson's disease (PD). However, actual pathophysiological mechanism underlying the anti-parkinsonian effect of zonisamide remains uncertain. Here we tested exactly the neuroprotective effect of zonisamide against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. We observed that zonisamide attenuated MPTP-induced dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) depletion in the striatum and reduced the loss of tyrosine hidroxylase (TH) positive neurons and the increase of glial fibrillary acidic protein (GFAP) positive astrocytes in the striatum and substantia nigra after 5 days. Our Western blot analysis study also showed that zonisamide can prevent the decrease of TH protein levels and increase of GFAP protein levels in the striatum 5 days after MPTP treatment. In the present study, on the other hand, zonisaimde treatment showed no significant changes of the striatal dopamine, DOPAC, and HVA content in the striatum of normal mice after 1 day, as compared to the vehicle-treated group. Furthermore, zonisamide produced a significant increase of the TH protein levels in the striatum after 1 day, as compared to vehicle-treated group. In contrast, zonisamide showed no significant changes of the GFAP protein levels in the striatum after 1 day, as compared to vehicle-treated group. These results show that anticonvulsant drug, zonisamide, has the neuroprotective effect in the MPTP model of PD in mice. Our study also demonstrates that the neuroprotective effect of zonisamide against dopaminergic cell damage may be mediated by the elevation of TH activity on dopaminergic system after MPTP treatment in mice. Our findings suggest that zonisamide may offer a new approach for the treatment of PD.

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Section: Discussionmentioning

confidence: 95%

A Novel Anti-Parkinsonian Agent, Zonisamide, Attenuates MPTP-Induced Neurotoxicity in Mice

et al. 2009

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“…It is a well known fact that long-term treatment of ʟ-dopa in PD patients causes various adverse side effects such as wearing-off, dyskinesia, psychiatric symptoms, and so on [44,45]. A recent study has demonstrated that treatment with a SSRI fluoxetine significantly suppressed ʟ-dopa-induced rotational behavior in 6-hydroxydopamine (6-OHDA)-treated rats with 5-HT 1A R-dependent manner [46].…”

Section: Discussionmentioning

confidence: 99%

Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson’s disease

et al. 2014

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BackgroundMirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson’s disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD.ResultsMale C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively.ConclusionOur results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment.

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“…Although there is not a cure for the disease, the most used and cheaper treatment for PD continues to be Levodopa, frequently accompanied by carbidopa or benserazide (Singer, 2012; Ossig and Reichmann, 2013). However, about 40% of patients developed motor fluctuations and dyskinesias after 4 to 6 years of treatment (Ogawa et al, 2005; Fernandez, 2012), demonstrating that further pharmacological research is needed in order to counterbalance these side effects.…”

Section: Introductionmentioning

confidence: 99%

Astrocytic modulation of blood brain barrier: perspectives on Parkinsonâ€™s disease

Cabezas

Ávila

González

et al. 2014

Front. Cell. Neurosci.

378

262

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The blood–brain barrier (BBB) is a tightly regulated interface in the Central Nervous System (CNS) that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson’s Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the ECs and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson’s disease (PD) and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

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L-DOPA treatment from the viewpoint of neuroprotection

Cited by 27 publications

References 102 publications

A Novel Anti-Parkinsonian Agent, Zonisamide, Attenuates MPTP-Induced Neurotoxicity in Mice

A Novel Anti-Parkinsonian Agent, Zonisamide, Attenuates MPTP-Induced Neurotoxicity in Mice

Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson’s disease

Astrocytic modulation of blood brain barrier: perspectives on Parkinsonâ€™s disease

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