Zinc Deprivation and the Nervous System

This review is concerned with the role of zinc in the function of the nervous system with emphasis on the effects of dietary zinc deprivation. Zinc deficiency leads to several pathological signs, some of which occur within a few days in growing animals deprived of zinc. Depletion eventually leads progressively to more severe behavioral changes, to abnormal stance, and to peripheral neuropathy. The nervous system contains many essential zinc metalloproteins that are highly stable, i.e. have high zinc association constants. These proteins, which include enzymes, transcription factors and storage proteins, do not become limiting during incipient zinc deficiency. It is likely that other, yet unidentified, zinc dependent proteins become limiting within a few days after animals are deprived of dietary zinc and lead to behavioral changes such as decreased and cyclic feeding. One candidate for the first limiting zinc component of nerve tissue is the "chelatable" zinc pool. Another is the plasma membrane zinc pool; the latter pool is decreased in zinc deficient rat erythrocytes, leading to oxidation of protein thiol groups and malfunction of that membrane. While the defective biochemical mechanism(s) that leads to the signs of deficiency is not entirely clear, there is evidence that synaptosomes from zinc deficient guinea pigs do not take up calcium normally when stimulated. It is postulated that the most vulnerable zinc pool serves a protective role against oxidative damage to plasma membrane proteins including the proteins involved with calcium channels. If so, the first limiting role of zinc is protective rather than catalytic or that of a neurotransmitter.