A5013999837- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Neurological disorders and treatments
- Neurotransmitter Receptor Influence on Behavior
- Nerve injury and regeneration
- Receptor Mechanisms and Signaling
- Nuclear Receptors and Signaling
- Botulinum Toxin and Related Neurological Disorders
- Diet and metabolism studies
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- Memory and Neural Mechanisms
- RNA regulation and disease
- Hypothalamic control of reproductive hormones
- Epilepsy research and treatment
- Ubiquitin and proteasome pathways
- Biochemical effects in animals
- Neuroendocrine regulation and behavior
- Spine and Intervertebral Disc Pathology
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Anesthesia and Pain Management
- Forensic Toxicology and Drug Analysis
- Psychedelics and Drug Studies
- Immune cells in cancer
Stanford University
2025
Université de Bordeaux
2001-2023
Centre National de la Recherche Scientifique
2007-2023
Motac Neuroscience (United Kingdom)
2013-2021
Institut des Maladies Neurodégénératives
2011-2020
Institut Interdisciplinaire de Neuroscience
2010
Victor (Japan)
2009
Galen University
2009
Abstract In Parkinson’s disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via vagus nerve, CNS. Here, we compare, in baboon monkeys, pathological consequences of either intrastriatal or injection α-synuclein-containing Lewy body extracts patients with disease. This study shows that patient-derived α-synuclein aggregates are able induce nigrostriatal lesions and system pathology after striatal a non-human primate model. finding suggests progression might be...
Gregory Porras1,2, Qin Li3 and Erwan Bezard1,2,3 1Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293 France 2CNRS, 3Institute of Lab Animal Sciences, China Academy Medical Beijing 100021, Correspondence: erwan.bezard{at}u-bordeaux2.fr
We have associated behavioral, pharmacological, and quantitative immunohistochemical study in a rat analog of l -DOPA-induced dyskinesia to understand whether alterations dopamine receptor fate striatal neurons may be involved mechanisms leading movement abnormalities. Detailed analysis at the ultrastructural level demonstrates specific D 1 (D R) subcellular localization medium spiny -DOPA-treated 6-hydroxydopamine-lesioned rats with abnormal involuntary movements (AIMs). This includes...
G protein–coupled receptor kinase 6, which promotes desensitization of the dopamine receptor, alleviates dyskinesia without compromising antiparkinsonian effect l -dopa.
The serotonin (5‐hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l ‐3,4‐dihydroxyphenylalanine (levodopa [l ‐dopa])–induced dyskinesia animal models Parkinson's disease. In fact, dopamine released a false transmitter from neurons appears to contribute pulsatile stimulation receptors, leading abnormal involuntary movements. Thus, drugs able dampen activity hold promise for treatment dyskinesia. authors investigated ability mixed 5‐HT 1A/1B...
l-DOPA–induced dyskinesia (LID), a detrimental consequence of dopamine replacement therapy for Parkinson’s disease, is associated with an alteration in D1 receptor (D1R) and glutamate interactions. We hypothesized that the synaptic scaffolding protein PSD-95 plays pivotal role this process, as it interacts D1R, regulates its trafficking function, overexpressed LID. Here, we demonstrate rat macaque models disrupting interaction between D1R striatum reduces LID development severity. Single...
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons as well presence proteinaceous inclusions named Lewy bodies. α-synuclein (α-syn) major constituent bodies, and first disease-causing protein in PD. Several α-syn-based animal models PD have been developed to investigate pathophysiology PD, but none them recapitulate full picture disease. Ageing most compelling risk factor for developing its impact on α-syn toxicity remains...
Chronic l -dopa treatment of Parkinson's disease (PD) often leads to debilitating involuntary movements, termed -dopa-induced dyskinesia (LID), mediated by dopamine (DA) receptors. RGS9–2 is a GTPase accelerating protein that inhibits DA D2 receptor-activated G proteins. Herein, we assess the functional role on LID. In monkeys, Western blot analysis striatal extracts shows levels are not altered MPTP-induced denervation and/or chronic administration. MPTP monkeys with LID, overexpression –...
Background The A11 diencephalospinal pathway is crucial for sensorimotor integration and pain control at the spinal cord level. When disrupted, it thought to be involved in numerous painful conditions such as restless legs syndrome migraine. Its anatomical organization, however, remains largely unknown non-human primate (NHP). We therefore characterized anatomy of this NHP. Methods Findings In situ hybridization dopamine receptors showed that D1 receptor mRNA absent while D2 D5 mRNAs are...
L-dopa remains the mainstay treatment for Parkinson's disease (PD), although in later stages, is complicated by L-dopa-induced dyskinesias (LID). Current evidence links LID to excessive striatal L-dopa-derived dopamine (DA) release, while possibility of a direct involvement itself has been largely ignored. Here we show that can alter basal ganglia activity and produce without enhancing DA release parkinsonian non-human primates. These data may have therapeutic implications management...
Machine learning–based approach unravels distinct pathological signatures induced by patient-derived α-synuclein seeds in monkeys.
The serotonin system has emerged as a potential target for anti-dyskinetic therapy in Parkinson's disease. In fact, neurons can convert L-DOPA into dopamine, and mediate its synaptic release. However, they lack feedback control mechanism able to regulate dopamine levels, which leads un-physiological stimulation of post-synaptic striatal receptors. Accordingly, drugs dampen the activity suppress L-DOPA-induced dyskinesia animal models Here, we investigated ability 5-HT1A/1B receptor agonist...
Abstract Background Preclinical evidence suggests that young plasma has beneficial effects on multiple organ systems in aged mice. Whether exerts an aging human population remains highly controversial. Despite lacking data, donor infusions have been promoted for age-related conditions. Given the preclinical by attenuating inflammation, this study examined whether administering a protein fraction to elderly would exert anti-inflammatory and immune modulating humans, using surgery as tissue...
Abstract Serotonin 3 (5‐HT ) receptors can affect motor control through an interaction with the nigrostriatal dopamine (DA) neurons, but neurochemical basis for this remains controversial. In study, using in vivo microdialysis, we assessed hypothesis that 5‐HT receptor‐dependent of striatal DA release is conditioned by degree and/or neuron activity and means (impulse‐dependent vs. impulse‐independent). The different DA‐releasing effects morphine (1 10 mg/kg), haloperidol (0.01 amphetamine...
Abstract Central serotonin 3 (5‐HT ) receptors control the mesoaccumbens dopamine (DA) pathway. This is thought to be conditional and might involve regionally distinct subpopulations of 5‐HT receptors. Here, using in vivo microdialysis rats, we assessed relative contribution nucleus accumbens (Nacc) overall influence exerted by on accumbal DA release induced different drugs or treatments. In freely moving pre‐treatment with antagonists (0.1 mg/kg ondansetron and/or 0.03 MDL 72222, s.c.)...
Aberrant membrane localization of dopamine D 1 receptor (D1R) is associated with l -DOPA-induced dyskinesia (LID), a major complication -DOPA treatment in Parkinson's disease (PD). Since the proteasome plays central role modulating neuronal response through regulation neurotransmitter intraneuronal fate, we hypothesized that ubiquitine-proteasome proteolytic pathway could be impaired LID. Those LIDs are actually striatum-specific decrease catalytic activity and accumulation polyubiquitinated...
Abstract In this study we investigated, using in vivo microdialysis and single unit recordings, the role of serotonin 4 (5‐HT ) receptors control nigrostriatal mesoaccumbal dopaminergic (DA) pathway activity. freely moving rats, 5‐HT antagonist GR 125487 (1 mg/kg, i.p.), without effect on its own, significantly reduced enhancement striatal DA outflow induced by 0.01 (−35%) 0.1 (−66%), but not 1 s.c. haloperidol (HAL). Intrastriatal infusion µ m had no influence basal outflow, attenuated...
Morphine is endogenously synthesized in the central nervous system and endogenous dopamine thought to be necessary for morphine formation. As Parkinson's disease results from loss of associated with pain, we considered how regulated untreated l-DOPA-treated parkinsonian brain. However, as cellular origin overall distribution remains obscure pathological adult brain, first characterized morphine-like compound immunoreactive cells rat striatum. We then studied changes immunoreactivity medium...
Synucleinopathies encompass several neurodegenerative diseases, which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. These diseases are characterized by the deposit of α-synuclein aggregates in intracellular inclusions neurons glial cells. Unlike disease bodies, where predominantly neuronal, atrophy is associated cytoplasmic oligodendrocytes. Glial pathological hallmark neuroinflammation, modest demyelination and, ultimately, neurodegeneration. To...
Abstract Aggregation of α-synuclein (α-syn) is the cornerstone neurodegenerative diseases termed synucleinopathies, which include Parkinson’s Disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA). These synucleinopathies are characterized by deposit aggregated α-syn in intracellular inclusions observable neurons glial cells. In PD DLB, these aggregates, predominantly located neurons, called (LBs). LBs one pathological hallmarks alongside dopaminergic neuron loss...