Zinc signaling in the hippocampus and its relation to pathogenesis of depression

Abstract

Zinc is released from glutamatergic (zincergic) neuron terminals in the brain, followed by the increase in Zn²⁺ concentration in the intracellular (cytosol) compartment as well as that in the extracellular compartment. Intracellular Zn²⁺ concentration mainly increases through calcium-permeable channels and serves as Zn²⁺ signal as well as extracellular Zn²⁺ concentration. Hippocampal Zn²⁺ signaling may participate in synaptic plasticity such as long-term potentiation and cognitive function. On the other hand, subclinical zinc deficiency is common in the old who might be more susceptible to depression. Zinc deficiency causes abnormal glucocorticoid secretion and increases depression-like behavior in animals. Neuropsychological symptoms are observed prior to the decrease in Zn²⁺ signal in the hippocampus under zinc deficiency. This paper summarizes that hippocampal Zn²⁺ signaling serves to maintain healthy brain and that glucocorticoid signaling, which is responsive to zinc homeostasis in the living body, is linked to the pathophysiology of depression.