NF-κB signalling regulates the growth of neural processes in the developing PNS and CNS

Abstract

The proper growth and elaboration of neural processes is essential for the establishment of a functional nervous system during development and is an integral feature of neural plasticity throughout life. Nuclear factor-kappa B(NF-κB) is classically known for its ubiquitous roles in inflammation,immune and stress-related responses and regulation of cell survival in all tissues, including the nervous system. NF-κB participation in other cellular processes remains poorly understood. Here we report a mechanism for controlling the growth of neural processes in developing peripheral and central neurons involving the transcription factor NF-κB. Inhibiting NF-κB activation with super-repressor IκB-α, BAY 11 7082(IκB-α phosphorylation inhibitor) or N-acetyl-Leu-Leu-norleucinal(proteosomal degradation inhibitor), or inhibiting NF-κB transcriptional activity with κB decoy DNA substantially reduced the size and complexity of the neurite arbors of sensory neurons cultured with brain-derived neurotrophic factor while having no effect on their survival. NF-κB exerted this effect during a restricted period of development following the phase of naturally occurring neuronal death when the processes and connections of the remaining neurons are extensively modified and refined. Inhibiting NF-κB activation or NF-κB transcriptional activity in layer 2 pyramidal neurons in postnatal somatosensory cortical slices reduced dendritic arbor size and complexity. This function of NF-κB has important implications for neural development and may provide an explanation for reported involvement of NF-κB in learning and memory.

Nuclear Factor κB-Dependent Neurite Remodeling Is Mediated by Notch Pathway

“…More recently, emerging data demonstrated its crucial involvement in regulating the growth and complexity of neuronal arborizations (Gutierrez et al, 2005;Gavaldà et al, 2009;Russo et al, 2009;Gutierrez and Davies, 2011) and in synaptic plasticity and memory in the adult brain (Albensi and Mattson, 2000;Kaltschmidt et al, 2006). Nevertheless, the mechanisms by which NF-B may exert such a role is largely unknown.…”

“…؊/؊ cortical neurons Previous studies demonstrated that NF-B signaling is involved in regulation of neurite outgrowth, size, and complexity of cortical neuron arborizations (Gutierrez et al, 2005(Gutierrez et al, , 2008Gavaldà et al, 2009). To gain insight into the role of NF-B in neuronal differentiation, we have taken advantage of the availability of mice carrying a homozygous deletion of the NF-B1 gene encoding the p50 subunit (Sha et al, 1995;Denis-Donini et al, 2008).…”

“…NF-B-dependent transcriptional activity becomes relevant in neurons when axons and dendrites grow and synapses are formed, and remains high under basal conditions in most regions of the adult brain (Mattson, 2005). NF-B signaling is also known to promote neurite outgrowth and to enhance the size and complexity of neuronal processes in the developing nervous system and in cultured neurons (Gutierrez et al, 2005;Gavaldà et al, 2009;Gutierrez and Davies, 2011). As for many other complex biological processes, the NF-B signaling pathway is likely to work in concert with others to regulate nerve cell survival and plasticity.…”

A Small Molecule Activator of p300/CBP Histone Acetyltransferase Promotes Survival and Neurite Growth in a Cellular Model of Parkinson’s Disease

“…Furthermore, in relation to PD-affected peripheral sympathetic neurons, p300/CBP has been shown to be an important transcriptional co-activator in the neuronal survival-and differentiation-inducing effects of NGF/NF-kappaB signalling (Chen et al 2010;Culmsee et al 2003;Wong et al 2005), which are essential regulators of neuronal development in the PNS (Davies 2009;Glebova and Ginty 2005;Gutierrez et al 2005;Gutierrez et al 2008). In addition to this, Hand2 is an important transcription factor for sympathetic nervous system development whose function is dependent on its interaction with p300/CBP (Morikawa et al 2005).…”

Negative Feedback Regulation of NF-κB Action by CITED2 in the Nucleus

“…The p65/p50 heterodimer is the predominant form of NF-kB in most cells, and it controls a wide array of genes critical in the immune response and inflammation (3). It might also play some potential roles in development (4,5). The aberrant action of NF-kB is causally associated with cancer (6) and some autoimmune diseases (7).…”