Acquired neuroprotection

Acquired neuroprotection is a synaptic activity dependent form of adaptation in the nervous system that renders neurons more resistant to harmful conditions. The term was coined by Hilmar Bading (1). This use-dependent enhancement of cellular survival activity requires changes in gene expression triggered by neuronal activity and nuclear calcium signaling. In rodents, components of the neuroprotective gene program can reduce brain damage caused by seizure-like activity or by a stroke (1, 2, 3). In acute and chronic neurodegenerative diseases, gene regulatory events important for acquired neuroprotection are antagonized by extrasynaptic NMDA receptor signaling leading to increased vulnerability, loss of structural integrity, and bioenergetics dysfunction (4, 5).

References

1) Zhang, S.J., Zou, M., Lu, L., Lau, D., Ditzel, D.A., Delucinge-Vivier, C., Aso, Y., Descombes, P., Bading, H. (2009) Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity. PLoS Genet 5: e1000604.

2) Zhang, S.J., Buchthal, B., Lau, D., Hayer, S., Dick, O., Schwaninger, M., Veltkamp, R., Zou, M., Weiss, U., Bading, H. (2011) A signaling cascade of nuclear calcium–CREB-ATF3 activated by synaptic NMDA receptors defines a gene repression module that protects against extrasynaptic NMDA receptor-induced neuronal cell death and ischemic brain damage. J. Neurosci. 31, 4978-4990.

3) Lau, D., Bengtson, C.P., Buchthal, B., Bading, H. (2015) BDNF reduces toxic extrasynaptic NMDA receptor signaling via synaptic NMDA receptors and nuclear calcium-induced transcription of inhba/Activin A. Cell Reports 12, 1353-1366.

4) Hardingham, G.E, Fukunaga, Y., and Bading, H. (2002) Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and death pathways. Nature Neuroscience 5, 405-415.

5) Hardingham, G.E., Bading, H. (2010) Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nature Reviews Neuroscience 11, 682-696.