title: Cognitive decline due to excess synaptic Zn(2+) signaling in the hippocampus.
abstract: Zinc is an essential component of physiological brain function. Vesicular zinc is released from glutamatergic (zincergic) neuron terminals and serves as a signal factor (Zn(2) (+) signal) in both the intracellular (cytosol) compartment and the extracellular compartment. Synaptic Zn(2) (+) signaling is dynamically linked to neurotransmission and is involved in processes of synaptic plasticity such as long-term potentiation and cognitive activity. On the other hand, the activity of the hypothalamic-pituitary-adrenal (HPA) axis, i.e., glucocorticoid secretion, which can potentiate glutamatergic neuron activity, is linked to cognitive function. HPA axis activity modifies synaptic Zn(2) (+) dynamics at zincergic synapses. An increase in HPA axis activity, which occurs after exposure to stress, may induce excess intracellular Zn(2) (+) signaling in the hippocampus, followed by hippocampus-dependent memory deficit. Excessive excitation of zincergic neurons in the hippocampus can contribute to cognitive decline under stressful and/or pathological conditions. This paper provides an overview of the ``Hypothesis and Theory'' of Zn(2) (+)-mediated modification of cognitive activity.
authors.affiliation: Department of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka Shizuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.affiliation: Department of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka Shizuoka, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Tamano
keywords: Zn2+ signal; cognition; glucocorticoid; glutamate; hippocampus