title: Importance of zinc in the central nervous system: the zinc-containing neuron.
abstract: 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.
authors.affiliation: NeuroBio Tex, Inc., Galveston, TX 77550, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Frederickson
authors.forename: S W
authors.initials: SW
authors.lastname: Suh
authors.forename: D
authors.initials: D
authors.lastname: Silva
authors.forename: C J
authors.initials: CJ
authors.lastname: Frederickson
authors.forename: R B
authors.initials: RB
authors.lastname: Thompson
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000502:physiology; D027682:Cation Transport Proteins; D002490:Central Nervous System / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D008967:Molecular Biology; D009474:Neurons / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000502:physiology; D015032:Zinc / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; C102806:SLC30A3 protein, human; D015032:Zinc