Antiparkinsonian Efficacy of Guanosine in Rodent Models of Movement Disorder.

Caio M Massari,Marc López-Cano,Víctor Fernández-Dueñas,Francisco Ciruela,Fabiana Núñez,Carla I Tasca

doi:10.3389/fphar.2017.00700

Abstract

Guanosine (GUO) is a guanine-based purine nucleoside with important trophic functions and promising neuroprotective properties. Although the neuroprotective effects of GUO have been corroborated in cellular models of Parkinson’s disease (PD), its efficacy as an antiparkinsonian agent has not been fully explored in PD animal models. Accordingly, we evaluated the effectiveness of GUO in reversing motor impairments in several rodent movement disorder models, including catalepsy, tremor, and hemiparkinsonism. Our results showed that orally administered GUO antagonized reserpine-mediated catalepsy, reduced reserpine-induced tremulous jaw movements, and potentiated the number of contralateral rotations induced by L-3,4-dihydroxyphenylalanine in unilaterally 6-hydroxidopamine-lesioned rats. In addition, at 5 and 7.5 mg/kg, GUO inhibited L-DOPA-induced dyskinesia in rats chronically treated with a pro-dopaminergic agent. Overall, we describe the therapeutic potential of GUO, which may be effective not only for reversing parkinsonian motor impairments but also for reducing dyskinesia induced by treatment for PD.

Highlights

Parkinson’s disease (PD) is a neurodegenerative condition of the central nervous system (CNS) characterized by bradykinesia, tremor, and rigidity (Poewe and Mahlknecht, 2009)
Adverse effects appear with the long consumption of dopaminergic drugs (Huot et al, 2013), among which dyskinesia - L-DOPA-induced dyskinesia (LID)- is one of most often reported and most likely to impede normal life
We assessed the ability of GUO to reduce reserpineinduced tremulous jaw movements (TJMs), a parameter known to ameliorate by antiparkinsonian drugs (Collins-Praino et al, 2011)

Summary

Introduction

Parkinson’s disease (PD) is a neurodegenerative condition of the central nervous system (CNS) characterized by bradykinesia, tremor, and rigidity (Poewe and Mahlknecht, 2009). The disorder, which is secondary to the loss of dopamine neurons in the substantia nigra, affects approximately 1% of the population over the age of 65 years (Meissner et al, 2011). Since the 1970s, the main therapeutic approach has consisted of administrating L-3,4-dihydroxyphenylalanine (L-DOPA) or other dopamine receptor agonists, aiming to reestablish normal function in the affected dopaminergic signaling circuitry (Poewe, 2009). Adverse effects appear with the long consumption of dopaminergic drugs (Huot et al, 2013), among which dyskinesia - L-DOPA-induced dyskinesia (LID)- is one of most often reported and most likely to impede normal life. Antiparkinsonian drugs are even classified clinically based on their probability of inducing dyskinesia, and it has been shown that rotating these drugs can diminish the appearance of these adverse motor effects. Novel agents are clearly needed to improve the management of PD (Schapira et al, 2006)

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