Article (Scientific journals)
The Neurogenic Potential of Astrocytes Is Regulated by Inflammatory Signals
MICHELUCCI, Alessandro; Bithell, Angela; Burney, Matthew et al.
2015In Molecular Neurobiology
Peer Reviewed verified by ORBi
 

Files


Full Text
Michelucci et al., Molecular Neurobiology, 2015.pdf
Publisher postprint (2.44 MB)
Request a copy

All documents in ORBilu are protected by a user license.

Send to



Details



Keywords :
Inflammation; Astrocytes; Neural stem cells; Noggin; NFκB; Epigenetic
Abstract :
[en] Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, adult parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, these ‘reactive’ astrocytes offer an alternative source of cells for central nervous system (CNS) repair following injury or disease. At present, the mechanisms that regulate the potential of different types of astrocytes are poorly understood. We used in vitro and ex vivo astrocytes to identify candidate pathways important for regulation of astrocyte potential. Using in vitro neural progenitor cell (NPC)-derived astrocytes, we found that exposure of more lineage-restricted astrocytes to either tumor necrosis factor alpha (TNF-α) (via nuclear factor-κB (NFκB)) or the bone morphogenetic protein (BMP) inhibitor, noggin, led to re-acquisition of NPC properties accompanied by transcriptomic and epigenetic changes consistent with a more neurogenic, NPC-like state. Comparative analyses of microarray data from in vitro-derived and ex vivo postnatal parenchymal astrocytes identified several common pathways and upstream regulators associated with inflammation (including transforming growth factor (TGF)-β1 and peroxisome proliferator-activated receptor gamma (PPARγ)) and cell cycle control (including TP53) as candidate regulators of astrocyte phenotype and potential. We propose that inflammatory signalling may control the normal, progressive restriction in potential of differentiating astrocytes as well as under reactive conditions and represent future targets for therapies to harness the latent neurogenic capacity of parenchymal astrocytes.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group)
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
MICHELUCCI, Alessandro ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Bithell, Angela;  University of Reading > School of Pharmacy, Department of Pharmacology
Burney, Matthew;  King’s College London > Institute of Psychiatry, Centre for the Cellular Basis of Behaviour
Johnston, Caroline;  King’s College London > Institute of Psychiatry, Centre for the Cellular Basis of Behaviour
Wong, Kee-Yew;  Genome Institute of Singapore
Teng, Siaw-Wei;  Genome Institute of Singapore
Desai, Jyaysi;  King’s College London > Institute of Psychiatry, Centre for the Cellular Basis of Behaviour
Gumbleton, Nigel;  University of Reading > School of Pharmacy, Department of Pharmacology
Anderson, Gregory;  King’s College London > Institute of Psychiatry, Centre for the Cellular Basis of Behaviour
Stanton, Lawrence;  Genome Institute of Singapore
Williams, Brenda;  King’s College London > Institute of Psychiatry, Centre for the Cellular Basis of Behaviour
Buckley, Noel;  University of Oxford > Department of Psychiatry
External co-authors :
yes
Language :
English
Title :
The Neurogenic Potential of Astrocytes Is Regulated by Inflammatory Signals
Publication date :
2015
Journal title :
Molecular Neurobiology
ISSN :
1559-1182
Publisher :
Humana Press, United States
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 04 April 2016

Statistics


Number of views
38 (2 by Unilu)
Number of downloads
1 (1 by Unilu)

Scopus citations®
 
31
Scopus citations®
without self-citations
28
OpenCitations
 
26
WoS citations
 
28

Bibliography


Similar publications



Contact ORBilu