NF-kappaB signalling regulates the growth of neural processes in the developing PNS and CNS.
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-kappaB) 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-kappaB 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-kappaB. Inhibiting NF-kappaB activation with super-repressor IkappaB-alpha, BAY 11 7082 (IkappaB-alpha phosphorylation inhibitor) or N-acetyl-Leu-Leu-norleucinal (proteosomal degradation inhibitor), or inhibiting NF-kappaB transcriptional activity with kappaB 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-kappaB 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-kappaB activation or NF-kappaB transcriptional activity in layer 2 pyramidal neurons in postnatal somatosensory cortical slices reduced dendritic arbor size and complexity. This function of NF-kappaB has important implications for neural development and may provide an explanation for reported involvement of NF-kappaB in learning and memory.
Gutierrez
Humberto
H
School of Biosciences, Biomedical Building, Museum Avenue, PO Box 911, Cardiff, CF10 3US, Wales. humberto.g@ed.ac.uk
Hale
Valerie A
VA
Dolcet
Xavier
X
Davies
Alun
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism; D017933:Peripheral Nervous System / Q000196:embryology* / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha