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Ascorbic Acid Attenuates Lead-Induced Alterations in the Synapses in the Developing Rat Cerebellum

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Abstract

We evaluated the effect of lead (Pb) and ascorbic acid treatment of pregnant female rats on cerebellar development in pups. Pb was administered in drinking water (0.2% Pb acetate), and ascorbic acid (100 mg/kg) was administered through oral intubation. Fifteen female rats were randomly classified into control, Pb, and Pb plus ascorbic acid (PA) groups. The treatment of Pb and ascorbic acid treatments were terminated after birth to evaluate the effects on the gestational development of the cerebellum. At postnatal day 21 (PND21), pups were sacrificed, and blood Pb level was analyzed. Blood Pb levels of pups and dams were highest in the Pb group and reduced in the PA group. Immunohistochemistry and immunoblot assays were conducted to study the cerebellar expression levels of synaptic proteins. Along with a significant reduction in Purkinje cells, the reduction in presynaptic (synaptophysin) and postsynaptic (postsynaptic density protein 95, N-methyl-d-aspartate receptor subtype 1) marker proteins was observed in Pb-exposed pups. Ascorbic acid treatment significantly prevented Pb-induced impairment in the cerebellar synaptic proteins. Hypothesizing that brain-derived neurotrophic factor (BDNF) might be affected by Pb exposure given its importance in the regulation of synaptogenesis, we observed a Pb-induced decrease and ascorbic acid-mediated increase of BDNF in the cerebellum. Luxol fast blue staining and myelin basic protein analysis suggest that ascorbic acid treatment ameliorated the Pb exposure-induced reduction in the axonal fibers in the developing cerebellum. Overall, we conclude that ascorbic acid treatment during pregnancy can prevent Pb-induced impairments in the cerebellar development in rats.

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Contributions

All authors conceived and designed the study. SMN, JSS, and JHL conducted animal modeling and histological analysis. ISC, THG, and BJC conducted animal caring and immunoblot analysis. SMN, ISC, BJC, and JHL collected and analyzed the data and wrote the manuscript. JHK and SSN participated in designing of the study, discussing of results, and revising the manuscript. All authors approved the final version of the manuscript.

Funding

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

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Author notes

  1. Sung Min Nam and In-Sun Cho contributed equally to this article.

Authors and Affiliations

  1. Department of Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea

    Sung Min Nam, In-Sun Cho, Jin Seok Seo, Tae-Hun Go, Sang-Soep Nahm, Byung-Joon Chang & Jong-Hwan Lee

  2. College of Veterinary Medicine and Veterinary Science Research Institute, Konkuk University, Seoul, 05030, Republic of Korea

    Sung Min Nam, Sang-Soep Nahm, Byung-Joon Chang & Jong-Hwan Lee

  3. Korea Bio-Safety Institute Co. Ltd, Eumseong, Chungbuk, 27600, Republic of Korea

    In-Sun Cho

  4. Department of Rehabilitation Psychology, Seoul Rehabilitation Hospital, Seoul, 03428, Republic of Korea

    Ji-Hye Kim

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  1. Sung Min Nam
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Correspondence to Byung-Joon Chang or Jong-Hwan Lee.

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Nam, S.M., Cho, IS., Seo, J.S. et al. Ascorbic Acid Attenuates Lead-Induced Alterations in the Synapses in the Developing Rat Cerebellum. Biol Trace Elem Res 187, 142–150 (2019). https://doi.org/10.1007/s12011-018-1354-6

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  • DOI: https://doi.org/10.1007/s12011-018-1354-6

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