446 research outputs found
Which species of NHP should be used to model PD?
No full text<p>This document encapsulates key recommendations resulting from the PD-AGE workshop, focusing on the critical decision of choosing non-human primate (NHP) species for modelling Parkinson's disease (PD) and understanding the impact of ageing on PD pathology. Through comprehensive discussions with experts, the workshop leaders discussed the irreplaceable role of NHP models and identified an ideal NHP species to model PD. The document provides a rationale for these choices and serves as a valuable guide for researchers navigating the selection of NHP species in PD and ageing studies, fostering informed decisions and advancing translational research in this crucial field.</p><p>The expert panel in this workshop was: Benjamin Dehay, Erwan Bezard, Jia-Yi Li, Romina Aron-Badin, Yoland Smith, Marina E. Emborg, Simon Borgognon, Ryosuke Takahashi, Jun Takahashi, John H Morrison, Rozalyn Anderson, Ashley Boehringer, Calista Holt, Julia Gambardella</p>
Which models of NHP should be used to study ageing?
No full text<p>This document encapsulates key recommendations resulting from the <a href="https://zenodo.org/records/10118883#">PD</a>-<a href="https://zenodo.org/records/10118883#">AGE</a> workshop, focusing on the critical decision of choosing non-human primate (NHP) species for modelling ageing and understanding the impact of <a href="https://zenodo.org/records/10118883#">ageing</a> on <a href="https://zenodo.org/records/10118883#">PD</a> pathology. Through comprehensive discussions with experts, the workshop leaders discussed the irreplaceable role of NHP models and identified an ideal NHP species to model <a href="https://zenodo.org/records/10118883#">PD</a>. The document provides a rationale for these choices and serves as a valuable guide for researchers navigating the selection of NHP species in <a href="https://zenodo.org/records/10118883#">PD</a> and <a href="https://zenodo.org/records/10118883#">ageing</a> studies, fostering informed decisions and advancing translational research in this crucial field.</p><p>The expert panel in this workshop was: Benjamin Dehay, Erwan Bezard, <a href="https://zenodo.org/records/10118883#">Jia</a>-Yi Li, Romina Aron-Badin, Yoland Smith, Marina E. Emborg, Simon Borgognon, Ryosuke Takahashi, Jun Takahashi, John H Morrison, Rozalyn Anderson, Ashley Boehringer, Calista Holt, Julia Gambardella</p>
Viral mediated α-synuclein overexpression results in greater transgene levels and α-synuclein overload in mice bearing kinase dead mutation of LRRK2
No full textAbstract The relationship between LRRK2 mutations and susceptibility to synuclein pathology in Parkinson’s disease (PD) is still unclear. We here investigate whether the mice carrying the D1994S kinase-dead (KD) mutation of LRRK2 show enhanced susceptibility to synucleinopathy. Twelve-month-old LRRK2 KD and WT mice were injected with AAV2/9 carrying human A53T α-synuclein (AAV-h-A53Tα-syn) or AAV2/9-GFP as a control. Three months after injection, α-synuclein pathology and nigrostriatal dopaminergic neuron degeneration were assessed along with motor behaviour. AAV-h-A53Tα-syn-injected LRRK2 KD mice showed a decline in stepping activity in the drag test compared to baseline levels and AAV-GFP-injected controls. This was associated with higher transgene levels and Serine129 α-syn phosphorylation in striatum and substantia nigra measured by immunohistochemistry. Total α-synuclein levels were also elevated in the substantia nigra but not striatum of AAV-h-A53Tα-syn LRRK2 KD mice compared to AAV-h-A53Tα-syn controls. Stereological counting of nigral dopaminergic neurons and densitometric analysis of striatal dopaminergic terminals did not reveal overt nigrostriatal degeneration. We conclude that silencing of kinase activity results in greater α-syn load due to greater viral transduction and/or defective α-syn clearance, possibly related to autophagy-lysosomal pathway impairment, however, with no consequence upon dopaminergic neuron survival in the mouse
A preclinical study on the combined effects of repeated eltoprazine and preladenant treatment for alleviating L-DOPA-induced dyskinesia in Parkinson's disease
No full textEltoprazine, a serotonergic (5-HT)1A/Breceptor 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 A2areceptor 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. The aim of this study was to investigate the daily repeated treatment effects of eltoprazine (1 mg/kg) alone, and in combination with preladenant (5 mg/kg), on the motor symptoms of PD and LID in MPTP-treated macaques. The anti-dyskinetic and âparkinsonian effects of combinative drug administration with a sub-threshold dose of L-DOPA were measured over 14 days. Eltoprazine treatment alone produced a near-complete suppression of dyskinesia but consistently increased parkinsonism. The administration of preladenant with eltoprazine prevented the increased severity of parkinsonian motor symptoms but was unable to maintain a reduced expression of dyskinesia with repeated administration. These data demonstrate the clinical utility of the modulation of the serotonergic and adenosine neurotransmitter systems with selective pharmacological agents for only acute treatment of LID. This multi-targeted approach is unsuitable as a long-term treatment regimen due to unsustainable therapeutic effects on dyskinesia
High-Frequency Stimulation of Both Zona Incerta and Subthalamic Nucleus Induces a Normalization of Basal Ganglia Metabolic Activity in Experimental Parkinsonism
No full textHigh-frequency stimulation (HFS) of the subthalamic nucleus( STN) alleviates dramatically motor symptoms in Parkinson's disease, and recently it has been suggested that zona incerta (ZI) stimulation might be as beneficial to patients. We used in situ cytochrome oxidase (Col) mRNA hybridization to investigate and compare the effects of HFS of the STN and the ZI on metabolic activity of the STN, globus pallidus (GP), and substantia nigra reticulata (SNr) in normal rats as well as in rats with 6 -hydroxydopamine (6-OHDA) lesion, an animal model of Parkinson's disease. In normal rats, HFS of the STN, as well as of the ZI, induced a significant decrease in Col mRNA expression within the STN and SNr but an increase within the GP. In 6-OHDA rats, HFS of the STN reversed dopamine denervation-induced changes in the expression of Col mRNA in the STN, SNr, and GP. Similar results were obtained with HFS of the ZI except for the STN, which showed only a trend toward nomlization. These data suggest that the ZI, as well as the STN, are implicated in the functional mechanism of HFS supporting the involvement of GABA transmission for the reduction of neuronal activity in the basal ganglia output structures
Mechanisms of L-DOPA-induced dyskinesia in Parkinson´s disease: What do animal models tell us?
No full textCould the serotonin theory give rise to a treatment for levodopa-induced dyskinesia in Parkinson's disease?
No full textInternational audienc
Magnetic resonance imaging characterisation of an α-synuclein model of Parkinson’s disease
No full textThis folder contains data used in the paper:Magnetic resonance imaging characterisation of an α-synuclein model of Parkinson’s disease Chirine KATRIB, Hector HLADKY, Kelly TIMMERMAN, Nicolas DURIEUX, Nathalie DUTHEIL, Erwan BEZARD, David DEVOS, Charlotte LALOUX and Nacim BETROUNI.To be pubished in European Journal of Neuroscience (Update October 2024).Please contact the corresponding author if you need further details about this work and dataNacim Betrouni, PhDFrench Natinal Institute of Health and Medical Research (INSERM)Lille NeuroScience & [email protected] DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV
La performance opérationnelle des ONG humanitaires : une analyse en termes d'enjeux institutionnels
No full text[eng] MISCELLANEOUS Erwan Quéinnec — The operational performance of humanitarian NGOs ; an analysis featuring institutional stakes . After two decades of almost unconditional success, ngos are now being questioned on their operational success mainly by funding agencies. So while the need for humanitarian services for beneficiary societies remains unchallenged, consensus still lacks on ways to conceive them. Indeed, beyond exhortations, humanitarian action is also belied by incentives, sanctions and institutional constraints. The author maintains that humanitarian action could in fact thrive without being really assessed, and as such appears to be resorting to a « resource economy » model.
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