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1. Induction of amyloid-β deposits from serially transmitted, histologically silent, Aβ seeds issued from human brains

Author

Herard, Anne-Sophie, Petit, Fanny, Gary, Charlotte, Guillermier, Martine, Boluda, Susana, Garin, Clément, Lam, Suzanne, Dhenain, Marc, Letournel, Franck, Martin-Negrier, Marie-Laure, Faisant, Maxime, Godfraind, Catherine, Maurage, Claude-Alain, Deramecourt, Vincent, Duchesne, Mathilde, Meyronnet, David, Maues De Paula, André, Rigau, Valérie, Burel-Vandenbos, Fanny, Duyckaerts, Charles, Seilhean, Danielle, Plu, Isabelle, Milin, Serge, Chiforeanu, Dan Christian, Laquerriere, Annie, Lannes, Béatrice, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuropathologie Raymond Escourolle, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), France-Alzheimer Association, Fondation Vaincre Alzheimer, CEA bottom-up program, NeurATRIS - ANR-11-INBS-0011, Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut des Neurosciences de Montpellier (INM)

Subjects
Genetically modified mouse, Pathology, medicine.medical_specialty, Amyloid, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Iatrogenic Disease, Mice, Transgenic, Plaque, Amyloid, Endogeny, Context (language use), Hippocampal formation, β-amyloid pathology, Hippocampus, lcsh:RC346-429, Pathology and Forensic Medicine, Lesion, Amyloid beta-Protein Precursor, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Presenilin-1, medicine, Animals, Humans, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, 0303 health sciences, Amyloid beta-Peptides, Tissue Extracts, Chemistry, Research, Amyloidosis, Brain, Human brain, Alzheimer's disease, medicine.disease, Immunohistochemistry, Disease Models, Animal, medicine.anatomical_structure, Neurology (clinical), medicine.symptom, Aβ transmission, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract

In humans, iatrogenic transmission of cerebral amyloid-β (Aβ)-amyloidosis is suspected following inoculation of pituitary-derived hormones or dural grafts presumably contaminated with Aβ proteins as well as after cerebral surgeries. Experimentally, intracerebral inoculation of brain homogenate extracts containing misfolded Aβ can seed Aβ deposition in transgenic mouse models of amyloidosis or in non-human primates. The transmission of cerebral Aβ is governed by the host and by the inoculated samples. It is critical to better characterize the propensities of different hosts to develop Aβ deposition after contamination by an Aβ-positive sample as well as to better assess which biological samples can transmit this lesion. Aβ precursor protein (huAPPwt) mice express humanized non-mutated forms of Aβ precursor protein and do not spontaneously develop Aβ or amyloid deposits. We found that inoculation of Aβ-positive brain extracts from Alzheimer patients in these mice leads to a sparse Aβ deposition close to the alveus 18 months post-inoculation. However, it does not induce cortical or hippocampal Aβ deposition. Secondary inoculation of apparently amyloid deposit-free hippocampal extracts from these huAPPwt mice to APPswe/PS1dE9 mouse models of amyloidosis enhanced Aβ deposition in the alveus 9 months post-inoculation. This suggests that Aβ seeds issued from human brain samples can persist in furtive forms in brain tissues while maintaining their ability to foster Aβ deposition in receptive hosts that overexpress endogenous Aβ. This work emphasizes the need for high-level preventive measures, especially in the context of neurosurgery, to prevent the risk of iatrogenic transmission of Aβ lesions from samples with sparse amyloid markers.

Published
2020

2. The Plasminogen Activation System Modulates Differently Adipogenesis and Myogenesis of Embryonic Stem Cells

Author

Hadadeh, Ola, Barruet, Emilie, Peiretti, Franck, Verdier, Monique, Bernot, Denis, Hadjal, Yasmine, El-Yazidi, Claire, Robaglia-Schlupp, Andrée, Maues de Paula, André, Nègre, Didier, Iacovino, Michelina, Kyba, Michael, Alessi, Marie-Christine, Binétruy, Bernard, HAL AMU, Administrateur, Fibrinolyse et Pathologie Vasculaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), and Xiao, Qingzhong

Subjects
General Science & Technology, Science, 1.1 Normal biological development and functioning, [SDV]Life Sciences [q-bio], Induced Pluripotent Stem Cells, Stem Cell Research - Embryonic - Non-Human, Regenerative Medicine, Muscle Development, Biochemistry, Mice, Plasminogen Activators, Underpinning research, Molecular Cell Biology, Serpin E2, Adipocytes, Animals, Enzyme-linked immunoassays, Biology, Embryonic Stem Cells, Muscle differentiation, Muscle Cells, Reverse transcriptase-polymerase chain reaction, Adipogenesis, Adipocyte differentiation, Stem Cells, Cell Differentiation, Plasminogen, Stem Cell Research, Extracellular Matrix, [SDV] Life Sciences [q-bio], Cytochemistry, Medicine, Protein expression, Cellular Types, Cloning, Research Article, Developmental Biology
Abstract

International audience; Regulation of the extracellular matrix (ECM) plays an important functional role either in physiological or pathological conditions. The plasminogen activation (PA) system, comprising the uPA and tPA proteases and their inhibitor PAI-1, is one of the main suppliers of extracellular proteolytic activity contributing to tissue remodeling. Although its function in development is well documented, its precise role in mouse embryonic stem cell (ESC) differentiation in vitro is unknown. We found that the PA system components are expressed at very low levels in undifferentiated ESCs and that upon differentiation uPA activity is detected mainly transiently, whereas tPA activity and PAI-1 protein are maximum in well differentiated cells. Adipocyte formation by ESCs is inhibited by amiloride treatment, a specific uPA inhibitor. Likewise, ESCs expressing ectopic PAI-1 under the control of an inducible expression system display reduced adipogenic capacities after induction of the gene. Furthermore, the adipogenic differentiation capacities of PAI-1 2/2 induced pluripotent stem cells (iPSCs) are augmented as compared to wt iPSCs. Our results demonstrate that the control of ESC adipogenesis by the PA system correspond to different successive steps from undifferentiated to well differentiated ESCs. Similarly, skeletal myogenesis is decreased by uPA inhibition or PAI-1 overexpression during the terminal step of differentiation. However, interfering with uPA during days 0 to 3 of the differentiation process augments ESC myotube formation. Neither neurogenesis, cardiomyogenesis, endothelial cell nor smooth muscle formation are affected by amiloride or PAI-1 induction. Our results show that the PA system is capable to specifically modulate adipogenesis and skeletal myogenesis of ESCs by successive different molecular mechanisms. Citation: Hadadeh O, Barruet E, Peiretti F, Verdier M, Bernot D, et al. (2012) The Plasminogen Activation System Modulates Differently Adipogenesis and Myogenesis of Embryonic Stem Cells. PLoS ONE 7(11): e49065.

Published
2012

3. Title: in vivo short TE localized 1 H MR spectroscopy of mouse cervical spinal cord at very high magnetic field (11.75T)

Author

Tachrount, Mohamed, Duhamel, Guillaume, Laurin, Jérôme, Marqueste, Tanguy, Maues De Paula, André, Decherchi, Patrick, Cozzone, Patrick, Callot, Virginie, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Grant support: ANR-09-BLAN-0295-01 (TRAUMATISM project) and CNRS Word count, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Genetically modified mouse, In vivo magnetic resonance spectroscopy, Male, 1h nmr spectroscopy, Magnetic Resonance Spectroscopy, Mouse, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Central nervous system, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, cervical spinal cord, 03 medical and health sciences, Mice, 0302 clinical medicine, Nuclear magnetic resonance, In vivo, medicine, Animals, Radiology, Nuclear Medicine and imaging, Tissue Distribution, Short TE, Reproducibility, business.industry, Multiple sclerosis, Reproducibility of Results, very high magnetic field, medicine.disease, Spinal cord, 3. Good health, Mice, Inbred C57BL, medicine.anatomical_structure, Spinal Cord, Cervical Vertebrae, Proton MRS, Protons, business, 030217 neurology & neurosurgery, Algorithms
Abstract

MR spectroscopy allows a noninvasive assessment of metabolic information in healthy and pathological central nervous system. Whereas MR spectroscopy has been extensively applied in the brain, only few spectroscopic studies of the spinal cord (SC) have been performed so far. For mice, due to additional technical challenges, in vivo 1H SC MRS has not yet been reported. In this work, the feasibility of short echo time localized proton magnetic resonance spectroscopy using Point RESolved Spectroscopy sequence for the examination of mouse cervical SC at 11.75 T is presented. Several optimizations were performed to improve the static field homogeneity, to reduce physiological motion effects and lipid contaminations arising from SC surrounding tissues, and to provide a careful metabolic quantification. Satisfactory spectrum quality was obtained. The described protocol allowed reliable quantification of five metabolites in the cervical SC. The mean reproducibility regarding the quantification of tNAA, tCr and tCho was ≥ 80%, > 70% for mI and > 55% for Glu, whereas the intersubject variabilities were ≤ 21%. The application of this protocol to transgenic mouse models in pathological conditions such as SC injury or neurodegenerative diseases may thus provide complementary information to MRI and increase our understanding of such pathologies. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.

Published
2012

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