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
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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.
KeywordsLead 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.
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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