Synaptic Zn2+ homeostasis and its significance

Abstract

The decrease in serum zinc is linked to the hypothalamic-pituitary-adrenal (HPA) axis activation that increases the serum glucocorticoid level, indicating the importance of zinc homeostasis in physiological function. Zinc homeostasis in the brain is maintained through the blood-brain and blood-cerebrospinal fluid barriers. At young age, however, the increase in zinc concentration in the brain extracellular fluid along with brain development is suppressed under chronic zinc deficiency, followed by suppression of the increase in zinc in the synaptic vesicles that serves as the Zn(2+) signal. Zn(2+) is released from glutamatergic (zincergic) neuron terminals and serves as the Zn(2+) signal in the intracellular (cytosol) compartment through calcium-permeable channels in addition to the extracellular compartment. Synaptic Zn(2+) signals may participate in synaptic plasticity such as long-term potentiation (LTP) and cognitive function. Both the lack and excess of synaptic Zn(2+) signals may affect them. Because there is limited evidence for the significance of Zn(2+) signaling, the exact relationship between synaptic Zn(2+) function and cognitive activity remains to be solved. Synaptic Zn(2+) homeostasis seems to be controlled by the two major pools of Zn(2+), i.e., the synaptic vesicle and the extracellular compartment, in the brain. Synaptic Zn(2+) homeostasis is affected by the enhanced glutamatergic (zincergic) neuron activity. This paper summarizes the significance of synaptic Zn(2+) homeostasis in zincergic neuron activity.