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L-DOPA rodent

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https://www.readbyqxmd.com/read/29372256/dopamine-deficiency-mediates-early-rod-driven-inner-retinal-dysfunction-in-diabetic-mice
#1
Moon K Kim, Moe H Aung, Lukas Mees, Darin E Olson, Nikita Pozdeyev, P Michael Iuvone, Peter M Thule, Machelle T Pardue
Purpose: Electroretinograms (ERGs) are abnormal in diabetic retinas before the appearance of vascular lesions, providing a possible biomarker for diabetic vision loss. Previously, we reported that decreased retinal dopamine (DA) levels in diabetic rodents contributed to early visual and retinal dysfunction. In the current study, we examined whether oscillatory potentials (OPs) could serve as a potential marker for detecting early inner retinal dysfunction due to retinal DA deficiency...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29242978/animal-models-of-l-dopa-induced-dyskinesia-the-6-ohda-lesioned-rat-and-mouse
#2
REVIEW
Elisabetta Tronci, Veronica Francardo
Appearance of L-DOPA-induced dyskinesia (LID) represents a major limitation in the pharmacological therapy with the dopamine precursor L-DOPA. Indeed, the vast majority of parkinsonian patients develop dyskinesia within 9-10 years of L-DOPA oral administration. This makes the discovery of new therapeutic strategies an important need. In the last decades, several animal models of Parkinson's disease (PD) have been developed, to both study mechanisms underlying PD pathology and treatment-induced side effects (i...
December 14, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29197517/dpi-289-a-novel-mixed-delta-opioid-agonist-mu-opioid-antagonist-dama-has-l-dopa-sparing-potential-in-parkinson-s-disease
#3
Tom H Johnston, Eboo Versi, Patrick A Howson, Paula Ravenscroft, Susan H Fox, Michael P Hill, Bruce E Reidenberg, Ronald Corey, Jonathan M Brotchie
L-DOPA-induced dyskinesia (LID) remains a significant problem in the management of Parkinson's disease (PD). In rodent and macaque models of PD, delta opioid receptor agonists have anti-parkinsonian actions while mu opioid antagonists can reduce the expression of LID. DPI-289 is a novel molecule with a unique combination of opioid receptor DAMA actions: delta agonist (Ki: 0.73 nM); mu antagonist (Ki: 12 nM). We demonstrated that DPI-289 has oral bioavailability and established its pharmacokinetic profile in both rat and primate...
November 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29102759/preclinical-profile-of-a-dopamine-d1-potentiator-suggests-therapeutic-utility-in-neurological-and-psychiatric-disorders
#4
Robert F Bruns, Stephen N Mitchell, Keith A Wafford, Alex J Harper, Elaine A Shanks, Guy Carter, Michael J O'Neill, Tracey K Murray, Brian J Eastwood, John M Schaus, James P Beck, Junliang Hao, Jeffrey M Witkin, Xia Li, Eyassu Chernet, Jason S Katner, Hong Wang, John W Ryder, Meghane E Masquelin, Linda K Thompson, Patrick L Love, Deanna L Maren, Julie F Falcone, Michelle M Menezes, Linli Zhang, Charles R Yang, Kjell A Svensson
DETQ, an allosteric potentiator of the dopamine D1 receptor, was tested in therapeutic models that were known to respond to D1 agonists. Because of a species difference in affinity for DETQ, all rodent experiments used transgenic mice expressing the human D1 receptor (hD1 mice). When given alone, DETQ reversed the locomotor depression caused by a low dose of reserpine. DETQ also acted synergistically with L-DOPA to reverse the strong hypokinesia seen with a higher dose of reserpine. These results indicate potential as both monotherapy and adjunct treatment in Parkinson's disease...
January 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29097596/ck2-oppositely-modulates-l-dopa-induced-dyskinesia-via-striatal-projection-neurons-expressing-d1-or-d2-receptors
#5
Marisol Cortés, Lauren Malave, Julia Castello, Marc Flajolet, M Angela Cenci, Eitan Friedman, Heike Rebholz
We have previously shown that casein kinase 2 (CK2) negatively regulates dopamine D1- and adenosine A2a receptor signaling in the striatum. Ablation of CK2 in D1-receptor-positive striatal neurons caused enhanced locomotion and exploration at baseline, whereas CK2 ablation in D2 receptor-positive neurons caused increased locomotion after treatment with A2a antagonist, caffeine. Since both, D1 and A2a receptors, play major roles in the cellular responses to L-DOPA in the striatum, these findings prompted us to examine the impact of CK2 ablation on the effects of L-DOPA treatment in the unilateral 6-OHDA lesioned mouse model of Parkinson's disease...
November 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29046640/antiparkinsonian-efficacy-of-guanosine-in-rodent-models-of-movement-disorder
#6
Caio M Massari, Marc López-Cano, Fabiana Núñez, Víctor Fernández-Dueñas, Carla I Tasca, Francisco Ciruela
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...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28939292/evolution-of-anti-parkinsonian-activity-of-monoterpenoid-1r-2r-6s-3-methyl-6-prop-1-en-2-yl-cyclohex-3-ene-1-2-diol-in-various-in-vivo-models
#7
Elena Valdman, Inga Kapitsa, Еlena Ivanova, Tat Iana Voronina, Oleg Ardashov, Konstantin Volcho, Veniamin Khazanov, Nariman Salakhutdinov
It has been found recently that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (Diol) demonstrates high antiparkinsonian activity in some animal models. We carried out an extended study of the antiparkinsonian activity of Diol in a set of relevant animal models. Diol (20mg/kg) exhibited an anticataleptogenic effect in the haloperidol-induced catalepsy model and restored motor activity in animals in the reserpine-induced model of oligokinesia. The ability of Diol singly administered before MPTP injection to reduce rigidity comparable to that of activity of L-DOPA (100mg/kg) was found using the model of Parkinsonian syndrome (PS) induced by single injection of MPTP (30mg/kg) to C57BL/6 mice...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28750831/potential-role-of-tyrosine-hydroxylase-in-the-loss-of-psychostimulant-effect-of-amphetamine-under-conditions-of-impaired-dopamine-transporter-activity
#8
Egle Janenaite, Valentina Vengeliene, Anton Bespalov, Berthold Behl
Amphetamine and methylphenidate are known to have stimulatory effect in healthy subjects but not in humans with attention deficit hyperactivity disorder and in rodents with impaired dopamine transporter (DAT) function. This phenomenon is called the paradoxical calming effect of psychostimulants. It has been previously demonstrated that psychostimulants may regulate the enzymatic activity of tyrosine hydroxylase (TH). Hence, the objective of the present study was to determine whether the lack of activity-stimulating effects of amphetamine in hyperactive rats is associated with changes in TH activity...
July 24, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28739086/a-preclinical-study-on-the-combined-effects-of-repeated-eltoprazine-and-preladenant-treatment-for-alleviating-l-dopa-induced-dyskinesia-in-parkinson-s-disease
#9
Wai Kin D Ko, Qin Li, Long Yun Cheng, Micaela Morelli, Manolo Carta, Erwan Bezard
Eltoprazine, a serotonergic (5-HT)1A/B receptor agonist, is a potential treatment for L-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD) but notably compromises the anti-parkinsonian effects of L-DOPA, as seen in rodent and monkey models of PD. Preladenant, a selective adenosine A2a receptor antagonist, mediates modest anti-parkinsonian effects in parkinsonian monkeys. In a recent investigation, combined eltoprazine and preladenant treatment with a sub-threshold dose of L-DOPA acutely attenuated dyskinesia without exacerbating PD disability in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques...
July 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28539659/involvement-of-the-bed-nucleus-of-the-stria-terminalis-in-l-dopa-induced-dyskinesia
#10
Matthieu F Bastide, Christelle Glangetas, Evelyne Doudnikoff, Qin Li, Mathieu Bourdenx, Pierre-Olivier Fernagut, Éric C Dumont, François Georges, Erwan Bézard
A whole brain immediate early gene mapping highlighted the dorsolateral bed nucleus of the stria terminalis (dlBST) as a structure putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID), the debilitating side-effects of chronic dopamine replacement therapy in Parkinson's disease (PD). dlBST indeed displayed an overexpression of ∆FosB, ARC, Zif268 and FRA2 only in dyskinetic rats. We thus hypothesized that dlBST could play a role in LID hyperkinetic manifestations. To assess the causal role of the dlBST in LID, we used Daun02 inactivation to selectively inhibit the electrical activity of dlBST ΔFosB-expressing neurons...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288194/the-aromatic-amino-acid-hydroxylase-genes-aah1-and-aah2-in-toxoplasma-gondii-contribute-to-transmission-in-the-cat
#11
Zi T Wang, Shiv K Verma, Jitender P Dubey, L David Sibley
The Toxoplasma gondii genome contains two aromatic amino acid hydroxylase genes, AAH1 and AAH2 encode proteins that produce L-DOPA, which can serve as a precursor of catecholamine neurotransmitters. It has been suggested that this pathway elevates host dopamine levels thus making infected rodents less fearful of their definitive Felidae hosts. However, L-DOPA is also a structural precursor of melanins, secondary quinones, and dityrosine protein crosslinks, which are produced by many species. For example, dityrosine crosslinks are abundant in the oocyst walls of Eimeria and T...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28286180/dysregulation-of-bet-proteins-in-levodopa-induced-dyskinesia
#12
David A Figge, David G Standaert
Levodopa (L-DOPA) remains the most effective pharmacological treatment for Parkinson Disease (PD) but its use is limited by the development of debilitating drug-related side effects, particularly L-DOPA induced dyskinesia (LID). LID is a consequence of long-term L-DOPA use, and in model systems is characterized by a "priming effect", whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent dopaminergic stimulation. Preliminary studies into the mechanisms underlying this cellular memory have indicated an important role for epigenetic change but many of the downstream mechanisms remain unknown...
June 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28268703/an-implantable-microelectrode-array-for-dopamine-and-electrophysiological-recordings-in-response-to-l-dopa-therapy-for-parkinson-s-disease
#13
Song Zhang, Yilin Song, Jun Jia, Guihua Xiao, Lili Yang, Min Sun, Mixia Wang, Xinxia Cai
Dual-mode multielectrode recordings have become routine in rodent neuroscience research. However, robust and reliable application of acute, multielectrode recording methods in brain especially for in vivo research remains a challenge. In patients with Parkinson's disease (PD), the efficacy of L-dopa therapy depends on its ability to restore Dopamine (DA) neurotransmission in the striatum. In this paper, We describe a low cost thin film 16 sites implantable microelectrode array (MEA) chip fabricated by standard lithography technology for in vivo test...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226891/an-implantable-microelectrode-array-for-dopamine-and-electrophysiological-recordings-in-response-to-l-dopa-therapy-for-parkinson-s-disease
#14
Song Zhang, Yilin Song, Jun Jia, Guihua Xiao, Lili Yang, Min Sun, Mixia Wang, Xinxia Cai, Song Zhang, Yilin Song, Jun Jia, Guihua Xiao, Lili Yang, Min Sun, Mixia Wang, Xinxia Cai, Xinxia Cai, Lili Yang, Guihua Xiao, Mixia Wang, Yilin Song, Song Zhang, Min Sun, Jun Jia
Dual-mode multielectrode recordings have become routine in rodent neuroscience research. However, robust and reliable application of acute, multielectrode recording methods in brain especially for in vivo research remains a challenge. In patients with Parkinson's disease (PD), the efficacy of L-dopa therapy depends on its ability to restore Dopamine (DA) neurotransmission in the striatum. In this paper, We describe a low cost thin film 16 sites implantable microelectrode array (MEA) chip fabricated by standard lithography technology for in vivo test...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28112685/chemogenetic-stimulation-of-striatal-projection-neurons-modulates-responses-to-parkinson-s-disease-therapy
#15
Cristina Alcacer, Laura Andreoli, Irene Sebastianutto, Johan Jakobsson, Tim Fieblinger, Maria Angela Cenci
Parkinson's disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathways' contribution to different motor features using SPN type-specific chemogenetic stimulation in rodent models of PD (PD mice) and L-DOPA-induced dyskinesia (LID mice)...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27764702/contribution-of-the-nitric-oxide-donor-molsidomine-and-the-antiparkinsonian-drug-l-dopa-to-the-modulation-of-the-blood-pressure-in-unilaterally-6-ohda-lesioned-rats
#16
Elżbieta Lorenc-Koci, Anna Czarnecka, Kinga Kamińska, Joanna Knutelska, Małgorzata Zygmunt, Magdalena Dudek
BACKGROUND: Interaction between dopaminergic and nitrergic neurotransmission in the brain plays a crucial role in the control of motor function and in the regulation of blood pressure (BP). In Parkinson's disease (PD), dopaminergic denervation of the striatum leads to disturbances in the nitrergic system in the basal ganglia. Recently, it has been demonstrated that addition of a low dose of the nitric oxide donor molsidomine to l-DOPA therapy improves dopaminergic neurotransmission in the denervated nigrostriatal system and weakens dyskinesias in rodent models of the disease...
February 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27733830/cannabidiol-prevents-motor-and-cognitive-impairments-induced-by-reserpine-in-rats
#17
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/27618286/l-dopa-induced-dyskinesia-in-parkinson-s-disease-are-neuroinflammation-and-astrocytes-key-elements
#18
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/27597526/validation-of-an-improved-scale-for-rating-l-dopa-induced-dyskinesia-in-the-mouse-and-effects-of-specific-dopamine-receptor-antagonists
#19
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/27596273/lack-of-antiparkinsonian-effects-of-systemic-injections-of-the-specific-t-type-calcium-channel-blocker-ml218-in-mptp-treated-monkeys
#20
Adriana Galvan, Annaelle Devergnas, Damien Pittard, Gunasingh Masilamoni, Jocelyn Vuong, J Scott Daniels, Ryan D Morrison, Craig W Lindsley, Thomas Wichmann
Dopaminergic medications ameliorate many of the motor impairments of Parkinson's disease (PD). However, parkinsonism is often only partially reversed by these drugs, and they can have significant side effects. Therefore, a need remains for novel treatments of parkinsonism. Studies in rodents and preliminary clinical evidence have shown that T-type calcium channel (TTCC) antagonists have antiparkinsonian effects. However, most of the available studies utilized nonselective agents. We now evaluated whether systemic injections of the specific TTCC blocker ML218 have antiparkinsonian effects in MPTP-treated parkinsonian Rhesus monkeys...
November 16, 2016: ACS Chemical Neuroscience
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