Article (Scientific journals)
Inflammation Promotes a Conversion of Astrocytes into Neural Progenitor Cells via NF-κB Activation
Gabel, Sebastien; Koncina, Eric; Dorban, Gauthier et al.
2015In Molecular Neurobiology, 53 (8), p. 5041-5055
Peer reviewed
 

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Keywords :
Astrocyte; Inflammation; NF-kB; Dedifferentiation; Neural progenitor cells
Abstract :
Brain inflammation, a common feature in neurodegenerative diseases, is a complex series of events, which can be detrimental and even lead to neuronal death. Nonetheless, several studies suggest that inflammatory signals are also positively influencing neural cell proliferation, survival, migration, and differentiation. Recently, correlative studies suggested that astrocytes are able to dedifferentiate upon injury and may thereby re-acquire neural stem cell (NSC) potential. However, the mechanism underlying this dedifferentiation process upon injury remains unclear. Here, we report that during the early response of reactive gliosis, inflammation induces a conversion of mature astrocytes into neural progenitors. A TNF treatment induces the decrease of specific astrocyte markers, such as glial fibrillary acidic protein (GFAP) or genes related to glycogen metabolism, while a subset of these cells re-expresses immaturity markers, such as CD44, Musashi-1, and Oct4. Thus, TNF treatment results in the appearance of cells that exhibit a neural progenitor phenotype and are able to proliferate and differentiate into neurons and/or astrocytes. This dedifferentiation process is maintained as long as TNF is present in the culture medium. In addition, we highlight a role for Oct4 in this process, since the TNF-induced dedifferentiation can be prevented by inhibiting Oct4 expression. Our results show that activation of the NF-κB pathway through TNF plays an important role in the dedifferentiation of astrocytes via the re-expression of Oct4. These findings indicate that the first step of reactive gliosis is in fact a dedifferentiation process of resident astrocytes mediated by the NF-κB pathway.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
University of Luxembourg: DLSM
Disciplines :
Life sciences: Multidisciplinary, general & others
Neurology
Biotechnology
Immunology & infectious disease
Author, co-author :
Gabel, Sebastien
Koncina, Eric ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Dorban, Gauthier
Heurtaux, Tony ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Birck, Cindy ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Glaab, Enrico  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Michelucci, Alessandro ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Heuschling, Paul ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC)
Grandbarbe, Luc
External co-authors :
no
Language :
English
Title :
Inflammation Promotes a Conversion of Astrocytes into Neural Progenitor Cells via NF-κB Activation
Publication date :
17 September 2015
Journal title :
Molecular Neurobiology
ISSN :
1559-1182
Publisher :
Humana Press, United States
Volume :
53
Issue :
8
Pages :
5041-5055
Peer reviewed :
Peer reviewed
Funders :
FNR - Fonds National de la Recherche [LU]
University of Luxembourg - UL
Available on ORBilu :
since 22 September 2015

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