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.

Improvement of Depression-Like Behavior and Memory Impairment with the Ethanol Extract of <i>Pleurotus eryngii</i> in Ovariectomized Rats

“…After ovariectomy, zinc level in hippocampal synaptosomes is significantly increased 18) but that in serum is lowered. 49) Also in our study, the amount of synaptosomal zinc was significantly increased by estrogen deficiency in OVX rats. Synaptic vesicles abundantly contain zinc, especially in hippocampal mossy fiber terminals.…”

“…Vesicular zinc is an important modulator of neurotransmission and is linked to the pathophysiology of depression. 14,15,50) It has been reported that a transient increase in zinc in hippocampal CA1 pyramidal neurons causes reversible memory deficit. 51) Therefore, appropriate zinc level is important for maintenance of normal neural functions.…”

Low dietary intake of magnesium is associated with increased externalising behaviours in adolescents

“…Mg is widely distributed in plant foods, particularly green leafy vegetables, legumes, nuts, seeds and whole grains. Zn is a cofactor of many enzymes that play a role in brain function (1) and is present in regions of the brain associated with the pathophysiology of mood disorders, including the amygdala, hippocampus and cerebral cortex (2) . Zn modulates neuronal excitability by inhibiting both the GABA (γ-aminobutyric acid) and NMDA (N-methyl-D-aspartate) receptors (3) and has shown antidepressant-like activities in animal models (4)(5)(6) .…”

Studies on stress-induced modulation of long term potentiation in rodent hippocampus: what can we learn about pathogenesis of depression?

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