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Neurodevelopmental Consequences of Dietary Zinc Deficiency: A Status Report

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Abstract

Zinc is a tightly regulated trace mineral element playing critical roles in growth, immunity, neurodevelopment, and synaptic and hormonal signaling. Although severe dietary zinc deficiency is relatively uncommon in the United States, dietary zinc deficiency is a substantial public health concern in low- and middle-income countries. Zinc status may be a key determinant of neurodevelopmental processes. Indeed, limited cohort studies have shown that serum zinc is lower in people diagnosed with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and depression. These observations have sparked multiple studies investigating the mechanisms underlying zinc status and neurodevelopmental outcomes. Animal models of perinatal and adult dietary zinc restriction yield distinct behavioral phenotypes reminiscent of features of ASD, ADHD, and depression, including increased anxiety and immobility, repetitive behaviors, and altered social behaviors. At the cellular and molecular level, zinc has demonstrated roles in neurogenesis, regulation of cellular redox status, transcription factor trafficking, synaptogenesis, and the regulation of synaptic architecture via the Shank family of scaffolding proteins. Although mechanistic questions remain, the current evidence suggests that zinc status is important for adequate neuronal development and may be a yet overlooked factor in the pathogenesis of several psychiatric conditions. This review aims to summarize current knowledge of the role of zinc in the neurophysiology of the perinatal period, the many cellular targets of zinc in the developing brain, and the potential consequences of alterations in zinc homeostasis in early life.

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Acknowledgements

We thank Jenna Gale for her helpful comments on the manuscript. This work was supported by National Institutes of Health grants NS043277 and NS117702 (EA). MMR is the recipient of the American Academy of Neurology Medical Student Research Scholarship (2022).

Funding

EA and DHE are supported by NIH grants NS043277 and NS117702. MMR is the recipient of the American Academy of Neurology Medical Student Research Scholarship (2022).

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  1. Department of Neurobiology and Pittsburgh Institute for Neurodegenerative Disorders, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA

    Madeline M. Ross, Diego R. Hernandez-Espinosa & Elias Aizenman

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  1. Madeline M. Ross
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  2. Diego R. Hernandez-Espinosa
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  3. Elias Aizenman
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MMR prepared and wrote the manuscript. DHE created the figures, reviewed, and edited the paper. EA reviewed and edited the paper. All authors read and approved the final manuscript.

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Correspondence to Elias Aizenman.

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Ross, M.M., Hernandez-Espinosa, D.R. & Aizenman, E. Neurodevelopmental Consequences of Dietary Zinc Deficiency: A Status Report. Biol Trace Elem Res 201, 5616–5639 (2023). https://doi.org/10.1007/s12011-023-03630-2

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