Severe Zinc Deficiency Causes the Loss and Apoptosis of Olfactory Ensheathing Cells (OECs) and Olfactory Deficit

Abstract

Dietary zinc deficiency may lead to olfactory deficits, whose mechanism remains largely elusive. Olfactory ensheathing cells (OECs), a type of glial cells that support the function and neurogenesis in the olfactory bulb (OB), may play a pivotal role in the maintenance of the olfactory system. In the present study, we established a rat model of dietary zinc deficiency and found that severe zinc deficiency, but not marginal zinc deficiency, caused significantly reduced food intake, growth retardation, and apparent olfactory deficit in growing rats. We showed that severe zinc deficiency resulted in the loss of OECs in the olfactory nerve layer (ONL) of the olfactory bulb. In addition, we revealed that the number of TUNEL-positive cells increased markedly in the region, suggesting an involvement of apoptotic cell death in zinc deficiency-induced loss of OECs. Moreover, we found that treatment with zinc chelator N,N,NN′,-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) triggered the apoptosis of in vitro-cultured primary OECs. The apoptosis of OECs was correlated with significantly elevated expression of p53. Importantly, TUNEL and CCK-8 assays both demonstrated that treatment with p53 antagonist pifithrin-α (PFT-α) markedly attenuated TPEN-induced OEC apoptosis. These findings implicated that p53-triggered apoptosis of OECs might play an integral role in zinc deficiency-induced olfactory malfunction.

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Abbreviations

OECs:

Olfactory ensheathing cells

OB:

Olfactory bulb

ppm:

Parts per million

TPEN:

N,N,NN′,-tetrakis (2-pyridylmethyl)ethylenediamine

PFT-α:

Pifithrin-α

NPCs:

Neural precursor cells

SVZ:

Subventricular zone

ROS:

Reactive oxidative species

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Availability of Data and Materials

All data and materials are available upon request.

Funding

This study was supported by the National Natural Science Foundation of China (81300720) and the Natural Science Foundation of Nantong University (12ZY029).

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CW designed the study. ZZ, GL, and YJ performed the study. JZ and CW analyzed the data. CW and YJ wrote the manuscript. All authors revised and approved the final version of the manuscript.

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Correspondence to Chunhua Wan.

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This research was approved by the Animal Care and Use Committee of Nantong University.

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Jiang, Y., Gu, L., Zhang, Z. et al. Severe Zinc Deficiency Causes the Loss and Apoptosis of Olfactory Ensheathing Cells (OECs) and Olfactory Deficit. J Mol Neurosci (2020). https://doi.org/10.1007/s12031-020-01709-2

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Keywords

  • Zinc deficiency
  • Olfactory deficit
  • Olfactory ensheathing cells
  • Apoptosis