Ascorbic Acid Supplementation Prevents the Detrimental Effects of Prenatal and Postnatal Lead Exposure on the Purkinje Cell and Related Proteins in the Cerebellum of Developing Rats

  • Sung Min Nam
  • Jin Seok Seo
  • Tae-Hun Go
  • Sang-Soep Nahm
  • Byung-Joon ChangEmail author


We investigated the effects of lead (Pb) and ascorbic acid co-administration on rat cerebellar development. Prior to mating, rats were randomly divided into control, Pb, and Pb plus ascorbic acid (PA) groups. Pregnant rats were administered Pb in drinking water (0.3% Pb acetate), and ascorbic acid (100 mg/kg) via oral intubation until the end of the experiment. Offspring were sacrificed at postnatal day 21, the age at which the morphology of the cerebellar cortex in developing pups is similar to that of the adult brain. In the cerebellum, Pb exposure significantly reduced Purkinje cells and ascorbic acid prevented their reduction. Along with the change of the Purkinje cells, long-term Pb exposure significantly reduced the expression of the synaptic marker (synaptophysin), γ-aminobutyric acid (GABA)–synthesizing enzyme (glutamic acid decarboxylase 67), and axonal myelin basic protein while ascorbic acid co-treatment attenuated Pb-mediated reduction of these proteins in the cerebellum of pups. However, glutamatergic N-methyl-d-aspartate receptor subtype 1 (NMDAR1), anchoring postsynaptic density protein 95 (PSD95), and antioxidant superoxide dismutases (SODs) were adversely changed; Pb exposure increased the expression of NMDAR1, PSD95, and SODs while ascorbic acid co-administration attenuated Pb-mediated induction. Although further studies are required about the neurotoxicity of the Pb exposure, the results presented here suggest that developmental Pb exposure disrupted normal development of Purkinje cells by increasing glutamatergic and oxidative stress in the cerebellum. Additionally, ascorbic acid co-treatment is beneficial in attenuating prenatal and postnatal Pb exposure–induced maldevelopment of Purkinje cells in the developing cerebellum.


Lead Ascorbic acid Cerebellum N-Methyl-d-aspartate receptor Glutamic acid decarboxylase 67 Superoxide dismutase 



SMN, JSS, THG, SSN, and BJC conceived the study and conducted the animal modeling, histological staining, and immunoblotting. SMN analyzed the data and wrote the manuscript. SSN and BJC participated in the writing of manuscript, design of the study, and subsequent discussion. All authors read and approved the final version of the manuscript.

Funding Information

This research was supported by the faculty research fund of Konkuk University and the Veterinary Science Research Institute of the Konkuk University.

Compliance with Ethical Standards

The protocol of the present study was approved by the Institutional Animal Care and Use Committee of the Konkuk University (approval number KU18133). All procedures were in accordance with the ethical standards of the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sung Min Nam
    • 1
    • 2
  • Jin Seok Seo
    • 1
  • Tae-Hun Go
    • 1
  • Sang-Soep Nahm
    • 1
    • 2
  • Byung-Joon Chang
    • 1
    • 2
    Email author
  1. 1.Department of Anatomy, College of Veterinary MedicineKonkuk UniversitySeoulRepublic of Korea
  2. 2.College of Veterinary Medicine and Veterinary Science Research InstituteKonkuk UniversitySeoulRepublic of Korea

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