Article (Scientific journals)
Regrowing the adult brain: NF-kappaB controls functional circuit formation and tissue homeostasis in the dentate gyrus.
Imielski, Yvonne; Schwamborn, Jens Christian; Luningschror, Patrick et al.
2012In PLoS ONE, 7 (2), p. 30838
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Keywords :
Animals; Apoptosis; Cyclic AMP-Dependent Protein Kinases/metabolism; Dentate Gyrus/cytology/metabolism/physiology; Forkhead Transcription Factors/metabolism; Gene Deletion; Gene Expression Regulation; Homeostasis; Inflammation/metabolism/pathology/physiopathology; Male; Mice; Mossy Fibers, Hippocampal/metabolism/physiology; NF-kappa B/deficiency/genetics/metabolism; Nerve Net/cytology/metabolism/physiology; Neurogenesis; Regeneration; Signal Transduction; Spatial Behavior/physiology
Abstract :
[en] Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-kappaB resulted in severe defects in the neurogenic region (dentate gyrus) of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-kappaB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-kappaB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-kappaB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-kappaB to be a therapeutic target for treating cognitive and mood disorders.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Imielski, Yvonne
Schwamborn, Jens Christian ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Luningschror, Patrick
Heimann, Peter
Holzberg, Magdalena
Werner, Hendrikje
Leske, Oliver
Puschel, Andreas W.
Memet, Sylvie
Heumann, Rolf
Israel, Alain
Kaltschmidt, Christian
Kaltschmidt, Barbara
More authors (3 more) Less
Language :
English
Title :
Regrowing the adult brain: NF-kappaB controls functional circuit formation and tissue homeostasis in the dentate gyrus.
Publication date :
2012
Journal title :
PLoS ONE
ISSN :
1932-6203
Publisher :
Public Library of Science, United States - California
Volume :
7
Issue :
2
Pages :
e30838
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 21 June 2013

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