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L-DOPA induced dyskinesia

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https://www.readbyqxmd.com/read/27902448/rasgrp1-promotes-amphetamine-induced-motor-behavior-through-a-rhes-interaction-network-rhesactome-in-the-striatum
#1
Neelam Shahani, Supriya Swarnkar, Vincenzo Giovinazzo, Jenny Morgenweck, Laura M Bohn, Catherina Scharager-Tapia, Bruce Pascal, Pablo Martinez-Acedo, Kshitij Khare, Srinivasa Subramaniam
The striatum of the brain coordinates motor function. Dopamine-related drugs may be therapeutic to patients with striatal neurodegeneration, such as Huntington's disease (HD) and Parkinson's disease (PD), but these drugs have unwanted side effects. In addition to stimulating the release of norepinephrine, amphetamines, which are used for narcolepsy and attention-deficit/hyperactivity disorder (ADHD), trigger dopamine release in the striatum. The guanosine triphosphatase Ras homolog enriched in the striatum (Rhes) inhibits dopaminergic signaling in the striatum, is implicated in HD and L-dopa-induced dyskinesia, and has a role in striatal motor control...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27882828/morinda-citrifolia-mitigates-rotenone-induced-striatal-neuronal-loss-in-male-sprague-dawley-rats-by-preventing-mitochondrial-pathway-of-intrinsic-apoptosis
#2
S Narasimhan Kishore Kumar, Jayakumar Deepthy, Uthamaraman Saraswathi, Mohan Thangarajeswari, Sathyamoorthy Yogesh Kanna, Pannerselvam Ezhil, Periandavan Kalaiselvi
OBJECTIVES: Parkinson disease (PD) is a neurodegenerative disorder affecting mainly the motor system, as a result of death of dopaminergic neurons in the substantia nigra pars compacta. The present scenario of research in PD is directed to identify novel molecules that can be administered individually or co-administered with L-Dopa to prevent the L-Dopa-Induced Dyskinesia (LID) like states that arise during chronic L-Dopa administration. Hence, in this study, we investigated whether Morinda citrifolia has therapeutic effects in rotenone-induced Parkinson's disease (PD) with special reference to mitochondrial dysfunction mediated intrinsic apoptosis...
November 24, 2016: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/27864045/influence-of-chronic-l-dopa-treatment-on-immune-response-following-allogeneic-and-xenogeneic-graft-in-a-rat-model-of-parkinson-s-disease
#3
Ludivine S Breger, Korbinian Kienle, Gaynor A Smith, Stephen B Dunnett, Emma L Lane
Although intrastriatal transplantation of fetal cells for the treatment of Parkinson's disease had shown encouraging results in initial open-label clinical trials, subsequent double-blind studies reported more debatable outcomes. These studies highlighted the need for greater preclinical analysis of the parameters that may influence the success of cell therapy. While much of this has focused on the cells and location of the transplants, few have attempted to replicate potentially critical patient centered factors...
November 15, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27859864/l-dopa-induced-dyskinesia-and-neuroinflammation-do-microglia-and-astrocytes-play-a-role
#4
Anna R Carta, Giovanna Mulas, Mariza Bortolanza, Terence Duarte, Elisabetta Pillai, Gilberto Fisone, Rita Vozari Raisman, Elaine Del Bel
In Parkinson's disease (PD), L-DOPA therapy leads to the emergence of motor complications including L-DOPA-induced dyskinesia (LID). LID relies on a sequence of pre- and postsynaptic neuronal events, leading to abnormal corticostriatal neurotransmission and maladaptive changes in striatal projection neurons. In recent years, additional non-neuronal mechanisms have been proposed to contribute to LID. Among these mechanisms considerable attention has been focused on L-DOPA-induced inflammatory responses. Microglia and astrocytes are the main actors in neuroinflammatory responses, and their double role at the interface between immune and neurophysiological responses is starting to be elucidated...
November 17, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27801563/functional-characterization-of-a-novel-series-of-biased-signaling-dopamine-d3-receptor-agonists
#5
Wei Xu, Xiaozhao Wang, Aaron M Tocker, Peng Huang, Maarten E A Reith, Lee-Yuan Liu-Chen, Amos B Smith Iii, Sandhya Kortagere
Dopamine receptors play an integral role in controlling brain physiology. Importantly sub-type selective agonists and antagonists of dopamine receptors with biased signaling properties have been successful in treating psychiatric disorders with a low incidence of side effects. To this end, we recently designed and developed SK609, a dopamine D3 receptor (D3R) selective agonist that has atypical signaling properties. SK609 has shown efficacy in reversing akinesia and reducing L-dopa-induced dyskinesia in a hemiparkinsonian rats...
November 1, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27771532/intrastriatal-injection-of-ionomycin-profoundly-changes-motor-response-to-l-dopa-and-its-underlying-molecular-mechanisms
#6
Chao Han, Shuke Nie, Guiqin Chen, Kai Ma, Nian Xiong, Zhentao Zhang, Yan Xu, Tao Wang, Stella M Papa, Xuebing Cao
Long-term l-DOPA treatment of Parkinson's disease is accompanied with fluctuations of motor responses and l-DOPA-induced dyskinesia (LID). Phosphorylation of the dopamine and c-AMP regulated phosphoprotein of 32kDa (DARPP-32) plays a role in the pathogenesis of LID, and thus dephosphorylation of this protein by activated calcineurin may help reduce LID. One important activator of calcineurin is the Ca(2+) ionophore ionomycin. Here, we investigated whether intrastriatal injection of ionomycin to hemiparkinsonian rats produced changes in l-DOPA responses including LID...
October 19, 2016: Neuroscience
https://www.readbyqxmd.com/read/27769404/determination-of-dopamine-serotonin-biosynthesis-precursors-and-metabolites-in-rat-brain-microdialysates-by-ultrasonic-assisted-in-situ-derivatization-dispersive-liquid-liquid-microextraction-coupled-with-uhplc-ms-ms
#7
Na Wei, Xian-En Zhao, Shuyun Zhu, Yongrui He, Longfang Zheng, Guang Chen, Jinmao You, Shu Liu, Zhiqiang Liu
This paper, for the first time, reported a simple, rapid, sensitive and environmental friendly ultrasonic-assisted in situ derivatization-dispersive liquid-liquid microextraction (in situ UAD-DLLME) method followed by ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of dopamine (DA), serotonin (5-HT) and their biosynthesis precursors and metabolites in rat brain microdialysates. In this work, a commercial reagent, Lissamine rhodamine B sulfonylchloride (LRSC), was proposed as a derivatization reagent...
December 1, 2016: Talanta
https://www.readbyqxmd.com/read/27733830/cannabidiol-prevents-motor-and-cognitive-impairments-induced-by-reserpine-in-rats
#8
Fernanda F Peres, Raquel Levin, Mayra A Suiama, Mariana C Diana, Douglas A Gouvêa, Valéria Almeida, Camila M Santos, Lisandro Lungato, Antônio W Zuardi, Jaime E C Hallak, José A Crippa, D'Almeida Vânia, Regina H Silva, Vanessa C Abílio
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson's disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson's disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27697481/differential-induction-of-dyskinesia-and-neuroinflammation-by-pulsatile-versus-continuous-l-dopa-delivery-in-the-6-ohda-model-of-parkinson-s-disease
#9
Giovanna Mulas, Elena Espa, Sandro Fenu, Saturnino Spiga, Giovanni Cossu, Elisabetta Pillai, Ezio Carboni, Gabriella Simbula, Dragana Jadžić, Fabrizio Angius, Stefano Spolitu, Barbara Batetta, Daniela Lecca, Andrea Giuffrida, Anna R Carta
Neuroinflammation is associated with l-DOPA treatment in Parkinson's disease (PD), suggesting a role in l-DOPA-induced dyskinesia (LID), however it is unclear whether increased inflammation is specifically related to the dyskinetic outcome of l-DOPA treatment. Diversely from oral l-DOPA, continuous intrajejunal l-DOPA infusion is associated with very low dyskinetic outcome in PD patients. We reproduced these regimens of administration in 6-OHDA-lesioned hemiparkinsonian rats, where dyskinetic responses and striatal neuroinflammation induced by chronic pulsatile (DOPAp) or continuous (DOPAc) l-DOPA were compared...
December 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27664460/the-impact-of-l-dopa-on-attentional-impairments-in-a-rat-model-of-parkinson-s-disease
#10
Elizabeth S Smith, Gwendolyn A Hardy, Timothy Schallert, Hongjoo J Lee
Attentional deficits including difficulty in switching attention between tasks or rules, sustaining attention, and selectively attending to specific stimuli are commonly seen in patients with Parkinson's disease (PD). While these deficits are frequently reported, it is unclear how traditional dopamine replacement therapy such as l-dopa affects these deficits. In a rat model of PD in which dopamine is unilaterally depleted with a 6-hydroxydopamine infusion to the medial forebrain bundle, we first examined the impact of acute and chronic l-dopa treatment on attention switching as modeled by disengagement behavior (i...
September 21, 2016: Neuroscience
https://www.readbyqxmd.com/read/27659966/altered-glutamate-release-in-the-dorsal-striatum-of-the-mitopark-mouse-model-of-parkinson-s-disease
#11
Ariana Q Farrand, Rebecca A Gregory, Cristina M Bäckman, Kristi L Helke, Heather A Boger
Mitochondrial dysfunction has been implicated in the degeneration of dopamine (DA) neurons in Parkinson's disease (PD). In addition, animal models of PD utilizing neurotoxins, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have shown that these toxins disrupt mitochondrial respiration by targeting complex I of the electron transport chain, thereby impairing DA neurons in these models. A MitoPark mouse model was created to mimic the mitochondrial dysfunction observed in the DA system of PD patients...
November 15, 2016: Brain Research
https://www.readbyqxmd.com/read/27618286/l-dopa-induced-dyskinesia-in-parkinson-s-disease-are-neuroinflammation-and-astrocytes-key-elements
#12
Elaine Del-Bel, Mariza Bortolanza, Maurício Dos-Santos-Pereira, Keila Bariotto, Rita Raisman-Vozari
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...
December 2016: Synapse
https://www.readbyqxmd.com/read/27613848/repetitive-transcranial-magnetic-stimulation-rtms-improves-behavioral-and-biochemical-deficits-in-levodopa-induced-dyskinetic-rats-model
#13
Maowen Ba, Min Kong, Lina Guan, Maoli Yi, Hongli Zhang
Fluctuations of dopamine levels and upregulations of NR2B tyrosine phosphorylation in the striatum have been connected with levodopa (L-dopa)-induced dyskinesia (LID) in Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) is one of the noninvasive and potential method treating dyskinesia. Yet, the effect of rTMS on the above key pathological events remains unclear. In this study, we gave L-dopa treatment intraperitoneally for 22 days to 6-hydroxydopamine-lesioned PD rats to prepare LID rats model, and subsequently applied rTMS daily for 3 weeks to LID rats model...
August 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27613437/l-dopa-oppositely-regulates-synaptic-strength-and-spine-morphology-in-d1-and-d2-striatal-projection-neurons-in-dyskinesia
#14
Luz M Suarez, Oscar Solis, Carolina Aguado, Rafael Lujan, Rosario Moratalla
Dopamine depletion in Parkinson's disease (PD) produces dendritic spine loss in striatal medium spiny neurons (MSNs) and increases their excitability. However, the synaptic changes that occur in MSNs in PD, in particular those induced by chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, are still poorly understood. We exposed BAC-transgenic D1-tomato and D2-eGFP mice to PD and dyskinesia model paradigms, enabling cell type-specific assessment of changes in synaptic physiology and morphology. The distinct fluorescence markers allowed us to identify D1 and D2 MSNs for analysis using intracellular sharp electrode recordings, electron microscopy, and 3D reconstructions with single-cell Lucifer Yellow injections...
September 9, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27597526/validation-of-an-improved-scale-for-rating-l-dopa-induced-dyskinesia-in-the-mouse-and-effects-of-specific-dopamine-receptor-antagonists
#15
Irene Sebastianutto, Natallia Maslava, Corey R Hopkins, M Angela Cenci
Rodent models of l-DOPA-induced dyskinesia (LID) are essential to investigate pathophysiological mechanisms and treatment options. Ratings of abnormal involuntary movements (AIMs) are used to capture both qualitative and quantitative features of dyskinetic behaviors. Thus far, validated rating scales for the mouse have anchored the definition of severity to the time during which AIMs are present. Here we have asked whether the severity of axial, limb, and orolingual AIMs can be objectively assessed with scores based on movement amplitude...
September 2, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27574484/palmitoyl-serotonin-inhibits-l-dopa-induced-abnormal-involuntary-movements-in-the-mouse-parkinson-model
#16
Hye-Yeon Park, Young-Kyoung Ryu, Jun Go, Eunjung Son, Kyoung-Shim Kim, Mee Ree Kim
L-3,4-dihydroxyphenylalanine (L-DOPA) is the most common treatment for patients with Parkinson's disease (PD). However, long term use of L-DOPA for PD therapy lead to abnormal involuntary movements (AIMs) known as dyskinesia. Fatty acid amide hydrolase (FAAH) is enriched protein in basal ganglia, and inhibition of the protein reduces dyskinetic behavior of mice. Palmitoyl serotonin (PA-5HT) is a hybrid molecule patterned after arachidonoyl serotonin, antagonist of FAAH. However, the effect of PA-5HT on L-DOPA-induced dyskinesia (LID) in PD have not yet been elucidated...
August 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/27452719/monoamine-transporter-contributions-to-l-dopa-effects-in-hemi-parkinsonian-rats
#17
Melissa M Conti, Samantha M Meadows, Mitchell Melikhov-Sosin, David Lindenbach, Joy Hallmark, David F Werner, Christopher Bishop
l-DOPA is the standard treatment for Parkinson's disease (PD), but chronic treatment typically leads to abnormal involuntary movement or dyskinesia (LID) development. Although poorly understood, dyskinetic mechanisms involve a complex interaction between the remaining dopamine system and the semi-homologous serotonin and norepinephrine systems. Serotonin and norepinephrine transporters (SERT and NET, respectively) have affinity for dopamine uptake especially when dopamine transporters (DAT) are scant. Monoamine reuptake inhibitors have been reported to modulate l-DOPA's anti-parkinsonian effects, but DAT, SERT, and NET's contribution to dyskinesia has not been well delineated...
November 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27424102/an-evaluation-of-istradefylline-treatment-on-parkinsonian-motor-and-cognitive-deficits-in-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-treated-macaque-models
#18
Wai Kin D Ko, Sandrine M Camus, Qin Li, Jianzhong Yang, Steve McGuire, Elsa Y Pioli, Erwan Bezard
Istradefylline (KW-6002), an adenosine A2A receptor antagonist, is used adjunct with optimal doses of L-3,4-dihydroxyphenylalanine (l-DOPA) to extend on-time in Parkinson's disease (PD) patients experiencing motor fluctuations. Clinical application of istradefylline for the management of other l-DOPA-induced complications, both motor and non-motor related (i.e. dyskinesia and cognitive impairments), remains to be determined. In this study, acute effects of istradefylline (60-100 mg/kg) alone, or with optimal and sub-optimal doses of l-DOPA, were evaluated in two monkey models of PD (i) the gold-standard 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model of parkinsonian and dyskinetic motor symptoms and (ii) the chronic low dose (CLD) MPTP-treated macaque model of cognitive (working memory and attentional) deficits...
November 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27418401/parkinsonian-monkeys-with-prior-levodopa-induced-dyskinesias-followed-by-fetal-dopamine-precursor-grafts-do-not-display-graft-induced-dyskinesias
#19
Jeffrey H Kordower, Angel Vinuela, Yaping Chu, Ole Isacson, D Eugene Redmond
Clinical trials testing the hypothesis that fetal dopamine grafts would provide antiparkinsonian benefit in patients who had already developed side-effects from their long-terms use of L-dopa revealed, in some cases, the presence of dyskinesias even in the absence of L-dopa. The form, intensity, and frequency of these dyskinesias were quite variable, but their manifestation slowed down the clinical development of cell replacement therapies. Rodent models of graft-induced dyskinesias (GIDs) have been proposed, however their accuracy in modeling GIDs has been questioned since they usually require amphetamine for their presentation...
July 15, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27373843/co-administration-of-cannabidiol-and-capsazepine-reduces-l-dopa-induced-dyskinesia-in-mice-possible-mechanism-of-action
#20
Maurício Dos-Santos-Pereira, Célia Aparecida da-Silva, Francisco Silveira Guimarães, Elaine Del-Bel
No abstract text is available yet for this article.
October 2016: Neurobiology of Disease
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