Zinc, redox regulation and brain development

Zinc is a component of the antioxidant defense system. Its functions protecting biological systems from oxidation are exerted at multiple levels including competing with redox active metals for binding sites, dynamically interacting with thiol groups and inducing metallothionein (MT) expression, regulating oxidant production, and increasing antioxidant defenses in part via NRF2 modulation. Zinc also directly and indirectly modulates redox regulated signaling cascades. Zinc deficits can affect not only the capacity of cells to defend against oxidative challenges but also alter redox signaling that modulate key cellular processes. Zinc is essential at different stages of development given its capacity to regulate key participating processes, e.g. cell proliferation, differentiation and survival. In the developing brain, the adverse consequences of a decrease in zinc availability depend on the severity and the timing of the deficiency. While gestational severe zinc deficiency causes teratogenesis in the brain and several other organs, mild zinc deficiency has significant deleterious consequences on the neural stem cell pool, neurogenesis, oligodendrogenesis, and astrogliogenesis in the offspring. Alterations in neuron, oligodendrocyte and astrocyte number, neuronal specification and myelination associated with zinc deficits in early development persist into adulthood, affecting behavior and motor performance. This review will focus on the role of zinc on brain development and on the interconnection between zinc and the redox tone in shaping different windows of neurodevelopment.