Regrowing the Adult Brain: NF-κB Controls Functional Circuit Formation and Tissue Homeostasis in the Dentate Gyrus

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Feb 8

PMID 22312433

Citations 39

Authors

Yvonne Imielski

Jens C Schwamborn

Patrick Luningschror

Peter Heimann

Magdalena Holzberg

Hendrikje Werner

Oliver Leske

Andreas W Puschel

Sylvie Memet

Rolf Heumann

Alain Israel

Christian Kaltschmidt

Barbara Kaltschmidt

Affiliations

Soon will be listed here.

Abstract

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-κB 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-κB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-κB 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-κB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-κB to be a therapeutic target for treating cognitive and mood disorders.

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