Intracellular Zn2+ signaling in cognition

Authors

  • Atsushi Takeda,

    Corresponding author
    1. Department of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
    2. Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
    • Correspondence to: Atsushi Takeda, Department of Bioorganic Chemistry &Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422–8526, Japan. E-mail: takedaa@u-shizuoka-ken.ac.jp

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  • Hiroaki Fujii,

    1. Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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  • Tatsuya Minamino,

    1. Department of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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  • Haruna Tamano

    1. Department of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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Abstract

Brain zinc homeostasis is strictly controlled under healthy conditions, indicating the importance of zinc for physiological function in the brain. A part of zinc in the brain exists in the synaptic vesicles, is released from a subclass of glutamatergic neurons (i.e., zincergic neurons), and serves as a signal factor (Zn2+ signal) in the intracellular (cytosol) compartment as well as in the extracellular compartment. Zn2+ signaling is dynamically linked to glutamate signaling and may be involved in synaptic plasticity, such as long-term potentiaion and cognitive activity. In zincergic synapses, intracellular Zn2+ signaling in the postsynaptic neurons, which is linked to Zn2+ release from zincergic neuron terminals, plays a role in cognitive activity. When nonzincergic synapses participate in cognition, on the other hand, it is possible that intracellular Zn2+ signaling, which is due mainly to Zn2+ release from the internal stores and/or metallothioneins, also is involved in cognitive activity, because zinc-dependent system such as zinc-binding proteins is usually required for cognitive process. Intracellular Zn2+ dynamics may be modified via an endocrine system activity, glucocorticoid secretion in both zincergic and nonzincergic neurons, which is linked to a long-lasting change in synaptic efficacy. On the basis of the evidence of cognitive decline caused by the lack and/or the blockade of synaptic Zn2+ signaling, this article summarizes the involvement of intracellular Zn2+ signaling in zincergic synapses in cognition and a hypothetical involvement of that in nonzincergic synapses. © 2014 Wiley Periodicals, Inc.

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