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Gaier ED, Eipper BA, Mains RE. Copper signaling in the mammalian nervous system: synaptic effects. J Neurosci Res. 2012;91(1):2-19doi: 10.1002/jnr.23143.
Gaier, E. D., Eipper, B. A., & Mains, R. E. (2013). Copper signaling in the mammalian nervous system: synaptic effects. Journal of neuroscience research, 91(1), 2-19. https://doi.org/10.1002/jnr.23143
Gaier, E D, et al. "Copper signaling in the mammalian nervous system: synaptic effects." Journal of neuroscience research vol. 91,1 (2013): 2-19. doi: https://doi.org/10.1002/jnr.23143
Gaier ED, Eipper BA, Mains RE. Copper signaling in the mammalian nervous system: synaptic effects. J Neurosci Res. 2013 Jan;91(1):2-19. doi: 10.1002/jnr.23143. Epub 2012 Nov 01. PMID: 23115049; PMCID: PMC3926505.
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J Neurosci Res. 2013 Jan;91(1):2-19. doi: 10.1002/jnr.23143. Epub 2012 Nov 01.

Copper signaling in the mammalian nervous system: synaptic effects.

Journal of neuroscience research

E D Gaier, B A Eipper, R E Mains

Affiliations

  1. Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030-3401, USA.

PMID: 23115049 PMCID: PMC3926505 DOI: 10.1002/jnr.23143

Abstract

Copper is an essential metal present at high levels in the CNS. Its role as a cofactor in mitochondrial ATP production and in essential cuproenzymes is well defined. Menkes and Wilson's diseases are severe neurodegenerative conditions that demonstrate the importance of Cu transport into the secretory pathway. In the brain, intracellular levels of Cu, which is almost entirely protein bound, exceed extracellular levels by more than 100-fold. Cu stored in the secretory pathway is released in a Ca(2+)-dependent manner and can transiently reach concentrations over 100 μM at synapses. The ability of low micromolar levels of Cu to bind to and modulate the function of γ-aminobutyric acid type A (GABA(A)) receptors, N-methyl-D-aspartate (NMDA) receptors, and voltage-gated Ca(2+) channels contributes to its effects on synaptic transmission. Cu also binds to amyloid precursor protein and prion protein; both proteins are found at synapses and brain Cu homeostasis is disrupted in mice lacking either protein. Especially intriguing is the ability of Cu to affect AMP-activated protein kinase (AMPK), a monitor of cellular energy status. Despite this, few investigators have examined the direct effects of Cu on synaptic transmission and plasticity. Although the variability of results demonstrates complex influences of Cu that are highly method sensitive, these studies nevertheless strongly support important roles for endogenous Cu and new roles for Cu-binding proteins in synaptic function/plasticity and behavior. Further study of the many roles of Cu in nervous system function will reveal targets for intervention in other diseases in which Cu homeostasis is disrupted.

Copyright © 2012 Wiley Periodicals, Inc.

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