Importance of zinc in the central nervous system: the zinc-containing neuron

J Nutr. 2000 May;130(5S Suppl):1471S-83S. doi: 10.1093/jn/130.5.1471S.


Zinc is essential to the structure and function of myriad proteins, including regulatory, structural and enzymatic. It is estimated that up to 1% of the human genome codes for zinc finger proteins. In the central nervous system, zinc has an additional role as a neurosecretory product or cofactor. In this role, zinc is highly concentrated in the synaptic vesicles of a specific contingent of neurons, called "zinc-containing" neurons. Zinc-containing neurons are a subset of glutamatergic neurons. The zinc in the vesicles probably exceeds 1 mmol/L in concentration and is only weakly coordinated with any endogenous ligand. Zinc-containing neurons are found almost exclusively in the forebrain, where in mammals they have evolved into a complex and elaborate associational network that interconnects most of the cerebral cortices and limbic structures. Indeed, one of the intriguing aspects of these neurons is that they compose somewhat of a chemospecific "private line" of the mammalian cerebral cortex. The present review outlines (1) the methods used to discover, define and describe zinc-containing neurons; (2) the neuroarchitecture and synaptology of zinc-containing neural circuits; (3) the physiology of regulated vesicular zinc release; (4) the "life cycle" and molecular biology of vesicular zinc; (5) the importance of synaptically released zinc in the normal and pathological processes of the cerebral cortex; and (6) the role of specific and nonspecific stressors in the release of zinc.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / pathology
  • Animals
  • Brain / anatomy & histology
  • Brain / metabolism*
  • Brain / pathology
  • Carrier Proteins / physiology
  • Cation Transport Proteins*
  • Central Nervous System / physiology*
  • Humans
  • Membrane Proteins / physiology
  • Molecular Biology
  • Neurons / physiology*
  • Synaptic Vesicles / metabolism
  • Synaptic Vesicles / physiology
  • Zinc / physiology*


  • Carrier Proteins
  • Cation Transport Proteins
  • Membrane Proteins
  • SLC30A3 protein, human
  • Zinc