Microglia are the resident immune cells of the central nervous system (CNS). When activated by tissue injury or other molecules released from damaged cells following CNS disorders such as brain ischemia and multiple sclerosis (MS), microglia retract their ramifications to form an activated amoeboid morphology. Recent studies have demonstrated that activated microglia can exert either pro-inflammatory or anti-inflammatory properties, which is thought to be regulated by factors in the microenvironment. On the other hand, zinc is concentrated in neurons of specific regions of the central nervous system (CNS) including the hippocampus and spinal cord. Massive amounts of zinc are released by neurons under severe conditions in which microglial activation occurs. This article discusses the role of extracellular zinc in regulation of microglial activation in animal models of brain ischemia and MS, as described in recent literatures by our group and the others. In addition, we review that zinc primes microglia via zinc-induced signaling pathway to enhance production of pro-inflammatory cytokines.
Zinc is an essential trace metal, it participates in biochemical reactions of various human bodies and its pharmacological activity is remarkably high, and its deficiency induced various pathological symptoms. On the other hand, when its zinc concentration in plasma is high, cytotoxicity develops as a side effect. For this reason, it exhibits effective pharmacological activity by sustained release of zinc over a long period of time in a trace amount. Zinc-containing calcium phosphate compounds in which zinc were substituted for calcium in a calcium phosphate compound were metastable crystals. The crystalline solids were able to develop a pharmacological effect of releasing zinc slowly by transferring to hydroxyapatite which was a stable form crystal in the living body and efficiently improving bone density. In addition, calcium phosphate compounds containing zinc, magnesium and fluorine were synthesized, and sustained release of zinc were confirmed, respectively. When these compounds were applied to osteoporotic rats, improvement of bone density and increased of bone strength were confirmed.
The essential trace element selenium (Se) plays a fundamental role in human health. Plant foods, such as vegetables, serve as the most common dietary sources of Se. Recently, novel seleno-amino acids, including Se-methylselenocysteine, γ-glutamyl-Se-methylselenocysteine, and selenocystathionine, have been found in certain plants and their benefits for human health are increasingly being recognized. The common ice plant, Mesembryanthemum crystallinum L., is an edible halophyte that accumulates D-pinitol, which exerts an insulin-like effect. However, little is known about the metabolism of seleno-amino acids in the common ice plants. Here we show that the common ice plant exhibits relatively high tolerance to both selenite and selenate and accumulated Se upon treatment with inorganic Se compounds. Speciation analysis revealed that selenocystine, selenomethionine, and Se-methylselenocysteine were present in the leaf of the Se-treated common ice plant. Interestingly, a significant portion of these Se-amino acids was liberated by a protease treatment, suggesting that the common ice plant can metabolize the inorganic Se compounds to the seleno-amino acids that were eventually incorporated nonspecifically into proteins. This study shows that the Se-enriched common ice plant can be a healthy source of Se in the human diet.