Zinc deficiency and neurodevelopment: the case of neurons

Abstract

Zinc is essential for normal brain development. Gestational severe zinc deficiency can lead to overt fetal brain malformations. Although not teratogenic, suboptimal zinc nutrition during gestation can have long-term effects on the offspring's nervous system. This article will review current knowledge on the role of zinc in modulating neurogenesis and neuronal apoptosis as well as the proposed underlying mechanisms. A decrease in neuronal zinc causes cell cycle arrest, which in part involves a deregulation of select signals (ERK1/2, p53, and NF-κB). Zinc deficiency also induces apoptotic neuronal death through the intrinsic (mitochondrial) pathway, which can be triggered by the activation of the zinc-regulated enzyme caspase-3, and as a consequence of abnormal regulation of prosurvival signals (ERK1/2 and NF-κB). Alterations in the finely tuned processes of neurogenesis, neuronal migration, differentiation, and apoptosis, which involve the developmental shaping of the nervous system, could have a long-term impact on brain health. Zinc deficiency during gestation, even at the marginal levels observed in human populations, could increase the risk for behavioral/neurological disorders in infancy, adolescence, and adulthood.