Antiparkinsonian Efficacy of Guanosine in Rodent Models of Movement Disorder

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

doi:10.3389/fphar.2017.00700

Cited by 18 publications

(17 citation statements)

References 52 publications

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“…In addition, guanosine potentiated contralateral rotations induced by L-DOPA in unilaterally 6-hydroxydopamine (6-OHDA)-injured rats and displayed antidyskinetic efficacy in the L-DOPA-induced dyskinesia (LID) animal model. These results support the potential usefulness of guanosine in PD management, including its capacity to reduce dyskinesia when used in combination with L-DOPA (Massari et al, 2017 ).…”

Section: Neurotrophic and Neuroprotective Effects Of Gbpssupporting

confidence: 77%

Neuromodulatory Effects of Guanine-Based Purines in Health and Disease

Tasca

Lanznaster

Oliveira

et al. 2018

Front. Cell. Neurosci.

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The function of guanine-based purines (GBPs) is mostly attributed to the intracellular modulation of heteromeric and monomeric G proteins. However, extracellular effects of guanine derivatives have also been recognized. Thus, in the central nervous system (CNS), a guanine-based purinergic system that exerts neuromodulator effects, has been postulated. The thesis that GBPs are neuromodulators emerged from in vivo and in vitro studies, in which neurotrophic and neuroprotective effects of these kinds of molecules (i.e., guanosine) were demonstrated. GBPs induce several important biological effects in rodent models and have been shown to reduce seizures and pain, stabilize mood disorder behavior and protect against gliomas and diseases related with aging, such as ischemia or Parkinson and Alzheimer diseases. In vitro studies to evaluate the protective and trophic effects of guanosine, and of the nitrogenous base guanine, have been fundamental for understanding the mechanisms of action of GBPs, as well as the signaling pathways involved in their biological roles. Conversely, although selective binding sites for guanosine have been identified in the rat brain, GBP receptors have not been still described. In addition, GBP neuromodulation may depend on the capacity of GBPs to interact with well-known membrane proteins in glutamatergic and adenosinergic systems. Overall, in this review article, we present up-to-date GBP biology, focusing mainly on the mechanisms of action that may lead to the neuromodulator role of GBPs observed in neurological disorders.

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Section: Neurotrophic and Neuroprotective Effects Of Gbpssupporting

confidence: 77%

Neuromodulatory Effects of Guanine-Based Purines in Health and Disease

Tasca

Lanznaster

Oliveira

et al. 2018

Front. Cell. Neurosci.

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“…However, induction of oxidative stress, increased formation of the proinflammatory cytokines, mitochondrial dysfunction and induction of apoptosis are suggested as precipitating factorsfor PD[26].In the present study, 6-OHDA injection induced significant decrease in the striatal dopamine and total swim score associated with significant increase in the catalepsy score compared to the control group. This was in the same line with Beppe et al[27] and Massari et al[28] who reported that 6-OHDA induces loss of the dopaminergic neurons in the substantia nigra leading to decreased striatal dopamine. Zeng et al[5] suggested that the alteration of the behavioral tests induced by 6-OHDA can be attributed to disruption of the balance between the glutamatergic and GABAergic activities in the brain.…”

supporting

confidence: 89%

Effect of metformin and indole-3-carbinol on a rat model of Parkinson’s disease induced by 6-hydroxydopamine

Borg

Kabel

Abdel-Kareem

2020

BESPS

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Parkinson's disease (PD) is a motor system disorder caused by factors that lead to depletion of dopamine from the dopaminergic neurons in the substantia nigra. Mechanisms of PD include mitochondrial dysfunction, oxidative stress and neuroinflammation. Metformin is an old antidiabetic drug that has recently been shown to offer protective effects against many types of cancer, cardiovascular and neurodegenerative diseases. Indole-3-carbinol (I3C) is a phytochemical derived from the cruciform vegetables. Recently, I3C was proven to have antioxidant, anti-inflammatory and neuroprotective properties. The aim of this work was to study the effect of metformin and/or I3C on 6-hydroxydopamine (6-OHDA)-induced PD in rats. Sixty male Wistar rats were divided into 6 equal groups: Control; 6-OHDA, metformin + 6-OHDA; I3C + 6-OHDA; carboxymethyl cellulose + 6-OHDA and metformin + I3C + 6-OHDA group. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), transforming growth factor beta1 (TGF-β1), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GR), mitochondrial complex 1 activity, total swim score and catalepsy score were measured. The striatum was subjected to immunohistochemical examination. The combination between metformin and I3C induced significant increase in striatal SOD, GR, mitochondrial complex 1 activity and dopamine with significant decrease in striatal TNF-α, IL-6, TGF-β1, MDA and nuclear factor kappa-B expression with significant improvement in catalepsy and total swim scores better than the groups that received either I3C or metformin alone. So, metformin/I3C combination may represent a beneficial therapeutic modality for amelioration of 6-OHDAinduced PD in rats..

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“…and/or VU0255035 (10 mg/kg, i.p.) was administered, and 1.5 h later, catalepsy was measured as described previously (Massari et al, 2017;Taura et al, 2017). Briefly, using a stopwatch with a cutoff time of 120 s, the duration of an abnormal upright posture was measured, in which the forepaws of the mouse were placed on a horizontal wooden bar (0.6-cm diameter) that was located 4.5 cm above the floor.…”

Section: Horizontal Bar Testmentioning

confidence: 99%

“…was administered 1.5 h before the test and 22 ± 2 h after reserpine treatment. The tremulous jaw movements (TJMs) were measured with handoperated counters, as described previously (Massari et al, 2017). Briefly, the mice were placed individually in a glass cylinder (13-cm diameter) and allowed to habituate for 10 min.…”

Section: Tremulous Jaw Movementsmentioning

confidence: 99%

Striatal Dopamine D2-Muscarinic Acetylcholine M1 Receptor–Receptor Interaction in a Model of Movement Disorders

et al. 2020

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor control deficits, which is associated with the loss of striatal dopaminergic neurons from the substantia nigra. In parallel to dopaminergic denervation, there is an increase of acetylcholine within the striatum, resulting in a striatal dopaminergiccholinergic neurotransmission imbalance. Currently, available PD pharmacotherapy (e.g., prodopaminergic drugs) does not reinstate the altered dopaminergic-cholinergic balance. In addition, it can eventually elicit cholinergic-related adverse effects. Here, we investigated the interplay between dopaminergic and cholinergic systems by assessing the physical and functional interaction of dopamine D 2 and muscarinic acetylcholine M 1 receptors (D 2 R and M 1 R, respectively), both expressed at striatopallidal medium spiny neurons. First, we provided evidence for the existence of D 2 R-M 1 R complexes via biochemical (i.e., co-immunoprecipitation) and biophysical (i.e., BRET 1 and NanoBiT R ) assays, performed in transiently transfected HEK293T cells. Subsequently, a D 2 R-M 1 R co-distribution in the mouse striatum was observed through doubleimmunofluorescence staining and AlphaLISA R immunoassay. Finally, we evaluated the functional interplay between both receptors via behavioral studies, by implementing the classical acute reserpine pharmacological animal model of experimental parkinsonism. Reserpinized mice were administered with a D 2 R-selective agonist (sumanirole) and/or an M 1 R-selective antagonist (VU0255035), and alterations in PD-related behavioral tasks (i.e., locomotor activity) were evaluated. Importantly, VU0255035 (10 mg/kg) potentiated the antiparkinsonian-like effects (i.e., increased locomotor activity and decreased catalepsy) of an ineffective sumanirole dose (3 mg/kg). Altogether, our data suggest the existence of putative striatal D 2 R/M 1 R heteromers, which might be a relevant target to manage PD motor impairments with fewer adverse effects.

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Antiparkinsonian Efficacy of Guanosine in Rodent Models of Movement Disorder

Cited by 18 publications

References 52 publications

Neuromodulatory Effects of Guanine-Based Purines in Health and Disease

Neuromodulatory Effects of Guanine-Based Purines in Health and Disease

Effect of metformin and indole-3-carbinol on a rat model of Parkinson’s disease induced by 6-hydroxydopamine

Striatal Dopamine D2-Muscarinic Acetylcholine M1 Receptor–Receptor Interaction in a Model of Movement Disorders

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