NF-kB in the Nervous System

Physiological effects of NF-kB within the nervous system

In the nervous system NF-kB is a transcription factor regulated by various extracellular stimuli such as neurotransmitters (glutamate), growth factors (NGF), proinflammatory cytokines (TNF) and others. We discovered that NF-kB is constitutively activate in mature glutamatergic neurons through continuous neurotransmission. In this line NF-kB is necessary for the normal physiological function of a neuron, that is survival and information processing/memory formation. NF-kB controls a neuroprotective gene expression program, which can protect neurons against various toxic substances such as A-beta peptides typically for Alzheimer´s disease.

pka-model 

Future projects

Under which conditions is NF-kB neuroprotective? Which molecular pathways are influenced by NF-kB in memory formation? How does NF-kB control neuronal circuits and neurogenesis in the adult aging hippocampus?
To study these questions we are using primary neuronal cultures and transgenic mouse models in which neuronal/glial NF-kB is repressed as well as approaches from systems biology.

hippocampus-ikb

Fig. 2: NF-kB regulates axonal (mossy) fiber projections in the brain (to CA3-region of the hippocampus). (d) Immunostaining for neurofilament M (NF-M) in control mice (IkB/-) reveals a fasciculated organisation of mossy fibers, connecting granule cells to their target cells in CA3. (e) Impairment of mossy fiber projections after neuronal NF-kB ablation (IkB/tTA). (f, g) Synaptophysin staining of synapses.

Transport of NF-kB in neurons

We found that NF-kB could be transported retrogradely back from the synapse to the nucleus. We study which motor proteins might be involved in this transport and what might be the physiological function. We are using live imaging,  proteomic techniques and super resolution light microscopy (sptPALM).

Neural stem cells

We are interested in signals which stimulate proliferation and differentiation of neural stem cells as well as the integration of newborn neurons into neuronal networks. We use several experimental paradigms: neurosphere cultures as well as transgenic mouse models. Moreover we could isolate neural stem cells from various sources including human tissues. We aim to develop the human stem cells as a cellular therapy for craniofacial lesions and neurodegenerative diseases.