Zinc is the second most abundant trace mineral in the body, and is commonly found in red meat, poultry, beans, breakfast cereals, and oysters. In our bodies, Zinc helps make proteins and support our cell structure. It plays a big role in our brains aiding in the development and maintenance of cell communication in the brain. On a cellular level, Zinc is key in regulating our cells’ life cycle specifically cell death which has an effect on the development of our brains. Zinc deficiency can lead to permanent physiological defects during brain development. This deficiency can also inhibit embryo growth causing abnormalities in the embryo size and nervous system.
Two very important proteins help zinc get around the body. The first family of proteins are called ZnT proteins. They are encoded in the SLC30A-(1-10) genes and help with moving zinc out of the cell. Additionally, ZnTs help with the compartmentalization of zinc and they have a very high sensitivity to zinc deficiency. The second family of proteins are called ZIP proteins. They are encoded in the SLC39A-(1-9) genes and help with moving zinc into the cell. In addition to these two proteins, a channel called the TRPM7 channel also helps with transporting zinc into the cell. This channel is especially important during embryonic development, and without it we see an increase in physiological brain abnormalities.
Zinc is crucial in the development and growth of embryos. In a recent study, pregnant mice who did not have the ZIP1 protein and pregnant mice who did not have ZIP1 and ZIP3 proteins were placed on a zinc-deficient diet. Scientists saw a range of effects on the embryos including a reduction in embryo size which is visible in figures 1A and 1C. Additionally, they saw poor development of the hindlimbs and forelimbs of the embryos. Zinc’s importance to the embryo during development was clear.
A shows the decrease in embryo and brain size when the mother is zinc deficient without ZIP1.
B shows the poor development of hindlimbs and forelimbs when the mother is zinc deficient without ZIP1.
C shows a decrease in embryo and brain size when the mother is zinc deficient without ZIP1 and ZIP3.
Zinc also plays a crucial and specific role in the development of the brain and closure of the neural tubes outlined in the images in Figure 2. In this study, scientists used TPEN to segregate and isolate zinc from its roles in development. TPEN is a zinc chelator- which means it sequesters zinc from the system. They used varying amounts of TPEN and zinc to show that when zinc is isolated brain development is impaired. In Figure A scientists showed how the brain develops normally with a normal amount of zinc present. This embryo had full development and neural tube closure. In comparison, they also tested how a dosage of TPEN would affect the embryo and how a high dosage of TPEN would affect the embryo’s brain development. With the lower dosage the embryo’s brain development happened normally with neural tube closure. However, with the higher dosage of TPEN more zinc is sequestered causing physiological abnormalities in the brain development and no neural tube closure. Finally, the scientists gave a high dose of TPEN followed by a dose of zinc sulfate which mitigated any effects of the TPEN allowing for normal brain development and neural tube closure. In Figure 3 the scientists examined how doses of TPEN significantly decreased the size of the mice embryos. In summary, zinc is essential for neural tube closure, growth, and development of the embryo.
A shows normal development of an embryo brain with neural tube closure.
B shows that with a low dose of TPEN the embryo’s brain develops normally with neural tube closure.
C shows with a high dose of TPEN the embryo’s brain is unable to develop normally with no neural tube closure.
D shows that with a high dose of TPEN followed by an addition of zinc, the effects of TPEN are reversible, and neural tube closure ensues with normal brain development.
Given the proven effects of zinc deficiency on embryonic development, a deeper understanding of zinc’s importance is vital to understanding other potentially zinc-related diseases. Conversations about zinc’s importance to development should be more prevalent, and a deeper understanding of zinc is desired. This provokes questions and understanding of how zinc deficiency plays a role in current diseases like Alzheimers and Parkinsons which have been implicated with excessive cell death, a result of zinc deficiency.
Sources:
Dufner‐Beattie, J., Huang, Z. L., Geiser, J., Xu, W., & Andrews, G. K. (2006). Mouse ZIP1 and ZIP3 genes together are essential for adaptation to dietary zinc deficiency during pregnancy. Genesis, 44(5), 239–251. https://doi.org/10.1002/dvg.20211
Li H, Zhang J, Niswander L. Zinc deficiency causes neural tube defects through attenuation of p53 ubiquitylation. Development. 2018 Dec 13;145(24):dev169797. doi: 10.1242/dev.169797. PMID: 30545932; PMCID: PMC6307889.