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357 results on '"Fernagut, Pierre-Olivier"'

16. A metabolic biomarker predicts Parkinson's disease at the early stages in patients and animal models

Author

Mallet, Da vid, Dufourd, Thibault, Decourt, Melina, Carcenac, Carole, Bossu, Paola, Verlin, Laure, Fernagut, Pierre-Olivier, Benoit-Marand, Marianne, Spalletta, Gianfranco, Barbier, Emmanuel L., Carnicella, Sebastien, Sgambato, Veronique, Fauvelle, Florence, and Boulet, Sabrina

Subjects
Medical research, Medicine, Experimental, Animal models in research -- Research, Metabolites -- Health aspects, Parkinson's disease -- Risk factors -- Diagnosis -- Development and progression, Biological markers -- Research, Health care industry
Abstract

BACKGROUND. Care management of Parkinson's disease (PD) patients currently remains symptomatic, mainly because diagnosis relying on the expression of the cardinal motor symptoms is made too late. Earlier detection of PD therefore represents a key step for developing therapies able to delay or slow down its progression. METHODS. We investigated metabolic markers in 3 different animal models of PD, mimicking different phases of the disease assessed by behavioral and histological evaluation, and in 3 cohorts of de novo PD patients and matched controls (n = 129). Serum and brain tissue samples were analyzed by nuclear magnetic resonance spectroscopy and data submitted to advanced multivariate statistics. RESULTS. Our translational strategy reveals common metabolic dysregulations in serum of the different animal models and PD patients. Some of them were mirrored in the tissue samples, possibly reflecting pathophysiological mechanisms associated with PD development. Interestingly, some metabolic dysregulations appeared before motor symptom emergence and could represent early biomarkers of PD. Finally, we built a composite biomarker with a combination of 6 metabolites. This biomarker discriminated animals mimicking PD from controls, even from the first, nonmotor signs and, very interestingly, also discriminated PD patients from healthy subjects. CONCLUSION. From our translational study, which included 3 animal models and 3 de novo PD patient cohorts, we propose a promising biomarker exhibiting a high accuracy for de novo PD diagnosis that may possibly predict early PD development, before motor symptoms appear. FUNDING. French National Research Agency (ANR), DOPALCOMP, Institut National de la Sante et de la Recherche Medicale, Universite Grenoble Alpes, Association France Parkinson., Introduction Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases in the world, affecting about 1% of adults older than 60 years (1). From its onset, the pathology [...]

Published
2022
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20. Recherche translationnelle sur les troubles cognitifs et comportementaux dans les maladies neurologiques et psychiatriques

Author

Azuar, Carole, Blin, Olivier, Checler, Frédéric, David, Denis J., Durif, Franck, Fernagut, Pierre-Olivier, Dupouey, Julien, Otten, Lisa, Gaillard, Raphaël, Kemel, Marie-Louise, Micallef, Joëlle, Perault-Pochat, Marie-Christine, Pitel, Anne-Lise, Truffinet, Philippe, Corvol, Jean-Christophe, Goni, Sylvia, and Bordet, Régis

Published
2016
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29. Neuropsychiatric and Cognitive Deficits in Parkinson’s Disease and Their Modeling in Rodents

Author

Decourt, Mélina, Jiménez-Urbieta, Haritz, Benoit-Marand, Marianne, Fernagut, Pierre-Olivier, Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), and Fernagut, Pierre-Olivier

Subjects
QH301-705.5, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Parkinson’s disease, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Review, Biology (General), non-motor symptoms, rodent models, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
Abstract

International audience; Parkinson’s disease (PD) is associated with a large burden of non-motor symptoms including olfactory and autonomic dysfunction, as well as neuropsychiatric (depression, anxiety, apathy) and cognitive disorders (executive dysfunctions, memory and learning impairments). Some of these non-motor symptoms may precede the onset of motor symptoms by several years, and they significantly worsen during the course of the disease. The lack of systematic improvement of these non-motor features by dopamine replacement therapy underlines their multifactorial origin, with an involvement of monoaminergic and cholinergic systems, as well as alpha-synuclein pathology in frontal and limbic cortical circuits. Here we describe mood and neuropsychiatric disorders in PD and review their occurrence in rodent models of PD. Altogether, toxin-based rodent models of PD indicate a significant but non-exclusive contribution of mesencephalic dopaminergic loss in anxiety, apathy, and depressive-like behaviors, as well as in learning and memory deficits. Gene-based models display significant deficits in learning and memory, as well as executive functions, highlighting the contribution of alpha-synuclein pathology to these non-motor deficits. Collectively, neuropsychiatric and cognitive deficits are recapitulated to some extent in rodent models, providing partial but nevertheless useful options to understand the pathophysiology of non-motor symptoms and develop therapeutic options for these debilitating symptoms of PD.

Published
2021

30. Mass spectrometry imaging identifies abnormally elevated brain l-DOPA levels and extrastriatal monoaminergic dysregulation in l-DOPA-induced dyskinesia

Author

Fridjonsdottir, Elva, Shariatgorji, Reza, Nilsson, Anna, Vallianatou, Theodosia, Odell, Luke R., Schembri, Luke S., Svenningsson, Per, Fernagut, Pierre-Olivier, Crossman, Alan R., Bezard, Erwan, Andrén, Per E., Uppsala University, Karolinska Institutet [Stockholm], Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), University of Manchester [Manchester], Motac Neuroscience [Manchester, UK], and Fernagut, Pierre-Olivier

Subjects
Dyskinesia, Drug-Induced, Dopamine, Neurosciences, SciAdv r-articles, Brain, Diseases and Disorders, Corpus Striatum, Mass Spectrometry, nervous system diseases, Levodopa, Disease Models, Animal, otorhinolaryngologic diseases, Animals, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Research Articles, Neurovetenskaper, Research Article, Neuroscience
Abstract

l-DOPA–induced dyskinesia is caused by elevated l-DOPA levels and dysregulated l-DOPA metabolism throughout the brain., l-DOPA treatment for Parkinson’s disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA–induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.

Published
2021

33. Age‐related behavioural and striatal dysfunctions in Shank3ΔC/ΔC mouse model of autism spectrum disorder.

Author

Thabault, Mathieu, Turpin, Valentine, Balado, Éric, Fernandes‐Gomes, Cloé, Huot, Anne‐Lise, Cantereau, Anne, Fernagut, Pierre‐Olivier, Jaber, Mohamed, and Galvan, Laurie

Subjects
AUTISM spectrum disorders, LABORATORY mice, ANIMAL disease models
Abstract

Autism spectrum disorders (ASDs) are defined as a set of neurodevelopmental disorders and a lifelong condition. In mice, most of the studies focused on the developmental aspects of these diseases. In this paper, we examined the evolution of motor stereotypies through adulthood in the Shank3ΔC/ΔC mouse model of ASD, and their underlying striatal alterations, at 10 weeks, 20 weeks, and 40 weeks. We highlighted that motor stereotypies worsened at 40 weeks possibly carried by earlier striatal medium spiny neurons (MSN) alterations in GABAergic transmission and morphology. Moreover, we report that 20 weeks could be a critical time‐point in the striatal‐related ASD physiopathology, and we suggest that MSN alterations may not be the direct consequence of developmental issues, but rather be a consequence of other impairments occurring earlier. [ABSTRACT FROM AUTHOR]

Published
2023
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34. Early diagnosis of Parkinson’s disease: A cross-species biomarker

Author

Mallet, David, primary, Dufourd, Thibault, additional, Decourt, Mélina, additional, Carcenac, Carole, additional, Bossù, Paola, additional, Verlin, Laure, additional, Fernagut, Pierre Olivier, additional, Benoit-Marand, Marianne, additional, Spalletta, Gianfranco, additional, Barbier, Emmanuel L, additional, Carnicella, Sebastien, additional, Sgambato, Véronique, additional, Fauvelle, Florence, additional, and Boulet, Sabrina, additional

Published
2021
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35. Impaired brain insulin signalling in Parkinson's disease

Author

Bassil, Fares, primary, Delamarre, Anna, additional, Canron, Marie‐Hélène, additional, Dutheil, Nathalie, additional, Vital, Anne, additional, Négrier‐Leibreich, Marie‐Laure, additional, Bezard, Erwan, additional, Fernagut, Pierre‐Olivier, additional, and Meissner, Wassilios G., additional

Published
2021
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38. Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinsonʼs disease

Author

Bastide, Matthieu F., Meissner, Wassilios G., Picconi, Barbara, Fasano, Stefania, Fernagut, Pierre-Olivier, Feyder, Michael, Francardo, Veronica, Alcacer, Cristina, Ding, Yunmin, Brambilla, Riccardo, Fisone, Gilberto, Jon Stoessl, A., Bourdenx, Mathieu, Engeln, Michel, Navailles, Sylvia, De Deurwaerdère, Philippe, Ko, Wai Kin D., Simola, Nicola, Morelli, Micaela, Groc, Laurent, Rodriguez, Maria-Cruz, Gurevich, Eugenia V., Quik, Maryka, Morari, Michele, Mellone, Manuela, Gardoni, Fabrizio, Tronci, Elisabetta, Guehl, Dominique, Tison, François, Crossman, Alan R., Kang, Un Jung, Steece-Collier, Kathy, Fox, Susan, Carta, Manolo, Angela Cenci, M., and Bézard, Erwan

Published
2015
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43. Transcription factor EB overexpression prevents neurodegeneration in experimental synucleinopathies

Author

Arotcarena, Marie-Laure, Bourdenx, Mathieu, Dutheil, Nathalie, Thiolat, Marie-Laure, Doudnikoff, Evelyne, Dovero, Sandra, Ballabio, Andrea, Fernagut, Pierre-Olivier, Meissner, Wassilios G., Bezard, Erwan, Dehay, Benjamin, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Politecnico di Milano [Milan] (POLIMI), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie et physiopathologie de la signalisation cellulaire (PPSC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Telethon Institute of Genetics and Medicine = Istituto Telethon di Genetica e Medicina (TIGEM), University of Naples Federico II, Baylor College of Medicine (BCM), Baylor University, CHU Bordeaux [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Fernagut, Pierre-Olivier, Interdisciplinary Institute for Neuroscience (IINS), Telethon Institute of Genetics and Medicine, Dehay, Benjamin, and University of Naples Federico II = Università degli studi di Napoli Federico II

Subjects
Male, [SDV]Life Sciences [q-bio], Therapeutics, Rats, Sprague-Dawley, Mice, Gene therapy, stomatognathic system, Cell Line, Tumor, mental disorders, Autophagy, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Brain, Parkinson Disease, Multiple System Atrophy, Rats, nervous system diseases, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Disease Models, Animal, Oligodendroglia, HEK293 Cells, nervous system, alpha-Synuclein, Parkinson’s disease, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Research Article, Neuroscience
Abstract

The synucleinopathies Parkinson’s disease (PD) and Multiple system atrophy (MSA) — characterized by α-synuclein intracytoplasmic inclusions into, respectively, neurons and oligodendrocytes — are associated with impairment of the autophagy-lysosomal pathways (ALP). Increased expression of the master regulator of ALP, transcription factor EB (TFEB), is hypothesized to promote the clearance of WT α-synuclein and survival of dopaminergic neurons. Here, we explore the efficacy of targeted TFEB overexpression either in neurons or oligodendrocytes to reduce the pathological burden of α-synuclein in a PD rat model and a MSA mouse model. While TFEB neuronal expression was sufficient to prevent neurodegeneration in the PD model, we show that only TFEB oligodendroglial overexpression leads to neuroprotective effects in the MSA model. These beneficial effects were associated with a decreased accumulation of α-synuclein into oligodendrocytes through recovery of the ALP machinery. Our study demonstrates that the cell type where α-synuclein aggregates dictates the target of TFEB overexpression in order to be protective, paving the way for adapted therapies., Targeted overexpression of transcription factor EB (TFEB) decreases accumulation of α-synuclein and prevents neurodegeneration in animal models of synucleinopathies.

Published
2019

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