Prion replication occurs in endogenous adult neural stem cells and alters their neuronal fate: involvement of endogenous neural stem cells in prion diseases

Autor: Claire Hamela, Carole Crozet, Danielle Casanova, Maxime Belondrade, Chantal Mourton-Gilles, Aroa Relano-Gines, Sylvain Lehmann, Audrey Gabelle
Přispěvatelé: Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Agence Nationale de Sécurité du Médicament et des produits de santé, ANSM, Fondation pour la Recherche Médicale, Paris, France, France Alzheimer Association, Paris, France, CDJ Foundation, Akron, Ohio, USA, European Project, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Frei, Monique, Food CT 2004 506579, European Netword of Excellence of Neuroprion - INCOMING
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
lcsh:Immunologic diseases. Allergy
[SDV.IMM] Life Sciences [q-bio]/Immunology
Prions
medicine.medical_treatment
Cellular differentiation
Immunology
Subventricular zone
Biology
Microbiology
Prion Diseases
Mice
03 medical and health sciences
0302 clinical medicine
Neural Stem Cells
Virology
Genetics
medicine
Animals
Molecular Biology
lcsh:QH301-705.5
Cells
Cultured
030304 developmental biology
0303 health sciences
Dentate gyrus
Neurogenesis
Stem-cell therapy
Neural stem cell
3. Good health
nervous system diseases
Neuroepithelial cell
Adult Stem Cells
Infectious Diseases
Mental Health
medicine.anatomical_structure
nervous system
lcsh:Biology (General)
Dentate Gyrus
Medicine
[SDV.IMM]Life Sciences [q-bio]/Immunology
Parasitology
lcsh:RC581-607
Neuroscience
030217 neurology & neurosurgery
Research Article
Adult stem cell
Zdroj: PLoS Pathogens, Vol 9, Iss 8, p e1003485 (2013)
PLoS Pathogens
PLoS Pathogens, Public Library of Science, 2013, 9 (8), pp.e1003485. ⟨10.1371/journal.ppat.1003485⟩
PLoS Pathogens, 2013, 9 (8), pp.e1003485. ⟨10.1371/journal.ppat.1003485⟩
ISSN: 1553-7374
1553-7366
DOI: 10.1371/journal.ppat.1003485⟩
Popis: Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocytosis, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders and stem cell therapy therefore represents an interesting new approach. Gains could not only result from the cell transplantation, but also from the stimulation of endogenous neural stem cells (NSC) or by the combination of both approaches. However, the development of such strategies requires a detailed knowledge of the pathology, particularly concerning the status of the adult neurogenesis and endogenous NSC during the development of the disease. During the past decade, several studies have consistently shown that NSC reside in the adult mammalian central nervous system (CNS) and that adult neurogenesis occurs throughout the adulthood in the subventricular zone of the lateral ventricle or the Dentate Gyrus of the hippocampus. Adult NSC are believed to constitute a reservoir for neuronal replacement during normal cell turnover or after brain injury. However, the activation of this system does not fully compensate the neuronal loss that occurs during neurodegenerative diseases and could even contribute to the disease progression. We investigated here the status of these cells during the development of prion disorders. We were able to show that NSC accumulate and replicate prions. Importantly, this resulted in the alteration of their neuronal fate which then represents a new pathologic event that might underlie the rapid progression of the disease.
Author Summary Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are considered to be caused by an abnormally folded infectious protein named PrPSc. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocyte proliferation, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders. Transplantation of stem cells, or the stimulation of endogenous neural stem cells (NSC) in the adult brain therefore constitute new interesting and promising strategies. While our first interest was the development of a cell therapy approach, we rapidly realised that there were a lot of questions to address before investigating pre-clinical cell therapy assays. Some of them were: (i) what is the status of endogenous neural stem cells during the development of prion diseases and can they amplify prions, and (ii) can they still proliferate and give rise to new neurons. In this study we definitely demonstrate that PrPSc was not only able to replicate in adult neural stem cells derived from infected brains but also that this results in an impairment of the production of their neuronal derivatives.
Databáze: OpenAIRE
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