The Role of Vesicular Zinc in Modulating Cell Proliferation and Survival in the Developing Hippocampus
Date
2022-09
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Abstract
In the brain, vesicular zinc, which refers to a subset of zinc that is sequestered into synaptic vesicles by zinc transporter 3 (ZnT3), has extensive effects in neuronal signaling and modulation. Vesicular zinc-focused research has mainly been directed to its role in the hippocampus, particularly in adult neurogenesis. However, whether vesicular zinc is involved in modulating neurogenesis during the early postnatal period has been less studied. To assess whether vesicular zinc plays a role in early developmental hippocampal neurogenesis, we used ZnT3 knockout (KO) mice, which lack ZnT3 and thus vesicular zinc, to evaluate cell proliferation at three different developmental age points, and the survival of these cells into adulthood. Our primary finding was that male ZnT3 KO mice exhibited lower rates of cell proliferation at P14, but higher numbers of these cells were retained to P60. Additionally, male and female ZnT3 KO mice retained a greater number of cells labelled on P6. These findings suggest that loss of vesicular zinc affects normal cell proliferation and cell survival at different age points during postnatal development. Additionally, we found sex-dependent differences whereby male mice showed higher levels of cell proliferation at P28, as well as higher levels of cell retention for P14-labelled cells, compared to female mice. There were also significant effects of age on cell proliferation and survival. Collectively, our findings offer novel insights into a unique role for vesicular zinc in the modulation of neurogenesis and cell survival during early postnatal development and highlight prominent sex- and age-dependent differences.
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Keywords
Zinc, ZnT3, Neurogenesis, Hippocampus, Development
Citation
Fu, S. (2022). The role of vesicular zinc in modulating cell proliferation and survival in the developing hippocampus (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.