Author
Christopher J. Frederickson
Other affiliations: Massachusetts Institute of Technology, University of Texas at Dallas, Aarhus University
Bio: Christopher J. Frederickson is an academic researcher from University of Texas Medical Branch. The author has contributed to research in topics: Zinc & Postsynaptic potential. The author has an hindex of 48, co-authored 97 publications receiving 12082 citations. Previous affiliations of Christopher J. Frederickson include Massachusetts Institute of Technology & University of Texas at Dallas.
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TL;DR: The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC, and the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'.
Abstract: The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'.
1,658 citations
TL;DR: This chapter discusses separate pools of CNS zinc, which are, vesicular zinc, free zinc, and protein-bound zinc; the enzymatic zinc is, therefore, a stable pool, involved only in the specific function of the zinc-containing enzymes.
Abstract: Publisher Summary This chapter discusses separate pools of CNS zinc, which are, vesicular zinc, free zinc, and protein-bound zinc Vesicular zinc is the one which is sequestered in the presynaptic vesicles of a special class of neurons, the zinc-containing neurons, which are found primarily in limbic, cerebrocortical, and corticofugal systems This vesicular zinc can be selectively stained by several histochemical procedures and is, therefore, accessible to histological and histoanalytical studies The second pool, free zinc, is an entirely hypothetical pool of ionic Zn +2 in the cytosol or interstitial fluid that may or may not be present in normal, healthy brain tissue The third pool of zinc is that which is bound firmly into the structure of the many zinc-containing enzymes in the brain The enzymatic zinc is, therefore, a stable pool, involved only in the specific function of the zinc-containing enzymes Zinc metalloenzymes are essential to the normal biology of brain cells, and any experimental treatment that is extreme enough to affect the metalloenzymes, such as prolonged zinc undernutrition or administration of chelators, can disrupt brain function through metalloenzymatic effects
1,075 citations
TL;DR: It is reported that the mossy-fibre neuropil and cells of origin (dentate granule cells) take up zinc preferentially, and that electrical stimulation selectively facilitates both uptake of exogenous zinc into mossY-f fibre neuro pil and release of previously incorporated 65Zn from the tissue.
Abstract: The mossy-fibre axons of the hippocampus form a dense plexus, uniquely rich in chelatable zinc. Because the metal is apparently concentrated within the terminal bags of the axons, it has been hypothesized that the zinc is involved in mossy-fibre synaptic transmission. Although some electrophysiological findings have favoured the hypothesis, neither preferential uptake of zinc into the hippocampus nor depolarization-induced release of zinc from hippocampal tissue has previously been found. Using the hippocampal slice preparation, we now report that the mossy-fibre neuropil and cells of origin (dentate granule cells) take up zinc preferentially, and that electrical stimulation selectively facilitates both uptake of exogenous zinc into mossy-fibre neuropil and release of previously incorporated 65Zn from the tissue. The results suggest that the role of zinc in mossy-fibre axons is dynamically linked to neural signalling processes.
822 citations
TL;DR: The present review outlines the methods used to discover, define and describe zinc-containing neurons; the neuroarchitecture and synaptology of zinc- containing neural circuits; the physiology of regulated vesicular zinc release; the "life cycle" and molecular biology of vesicle zinc; the importance of synaptically released zinc in the normal and pathological processes of the cerebral cortex; and the role of specific and nonspecific stressors in the release of zinc.
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.
800 citations
TL;DR: A histochemical method for staining CNS zinc by the stoichiometric formation of zinc: quinoline fluorescent chelates is described, and data indicate that the fluorochrome can be used for quantitative estimates of CNS zinc pools as well as qualitative studies of localization.
521 citations
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TL;DR: This work reviews those forms of LTP and LTD for which mechanisms have been most firmly established and examples are provided that show how these mechanisms can contribute to experience-dependent modifications of brain function.
3,767 citations
TL;DR: This review discusses International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
Abstract: The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
3,044 citations
TL;DR: A major unifying thread of the review is a consideration of how the changes occurring during and after ischemia conspire to produce damaging levels of free radicals and peroxynitrite to activate calpain and other Ca(2+)-driven processes that are damaging, and to initiate the apoptotic process.
Abstract: This review is directed at understanding how neuronal death occurs in two distinct insults, global ischemia and focal ischemia. These are the two principal rodent models for human disease. Cell dea...
2,960 citations
2,446 citations
TL;DR: The Hg(II) Detector simplifies the experimental setup by enabling a single amplifier to be switched between the Oligonucleotide-Based and DNAzyme-Based detectors.
Abstract: 9.2. Protein-Based Hg(II) Detectors 3467 9.3. Oligonucleotide-Based Hg(II) Detector 3467 9.4. DNAzyme-Based Hg(II) Detectors 3469 9.5. Antibody-Based Hg(II) Detector 3469 10. Mercury Detectors Based on Materials 3469 10.1. Soluble and Fluorescent Polymers 3469 10.2. Membranes, Films, and Fibers 3471 10.3. Micelles 3473 10.4. Nanoparticles 3473 11. Perspectives 3474 12. Addendum 3475 12.1. Small Molecules 3475 12.2. Biomolecules 3477 12.3. Materials 3477 13. List of Abbreviations 3477 14. Acknowledgments 3478 15. References 3478
2,139 citations