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Sodium p -Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels

Author

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  • Shao-Jun Li

    (Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
    Shao-Jun Li, Chao-Yan Ou, Sheng-Nan He and Xiao-Wei Huang contributed equally to this article.)

  • Chao-Yan Ou

    (Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
    Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China
    Shao-Jun Li, Chao-Yan Ou, Sheng-Nan He and Xiao-Wei Huang contributed equally to this article.)

  • Sheng-Nan He

    (Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
    Shao-Jun Li, Chao-Yan Ou, Sheng-Nan He and Xiao-Wei Huang contributed equally to this article.)

  • Xiao-Wei Huang

    (Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
    Shao-Jun Li, Chao-Yan Ou, Sheng-Nan He and Xiao-Wei Huang contributed equally to this article.)

  • Hai-Lan Luo

    (Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China)

  • Hao-Yang Meng

    (Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China)

  • Guo-Dong Lu

    (Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
    Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, China
    Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning 530021, China)

  • Yue-Ming Jiang

    (Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China)

  • Tanara Vieira Peres

    (Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer, 209, 1300 Morris Park Ave, Bronx, NY 10461, USA)

  • Yi-Ni Luo

    (Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China)

  • Xiang-Fa Deng

    (Department of Anatomy, School of Pre-Clinical Medicine, Guangxi Medical University, Nanning 530021, China)

Abstract

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl 2 (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABA A ) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism.

Suggested Citation

  • Shao-Jun Li & Chao-Yan Ou & Sheng-Nan He & Xiao-Wei Huang & Hai-Lan Luo & Hao-Yang Meng & Guo-Dong Lu & Yue-Ming Jiang & Tanara Vieira Peres & Yi-Ni Luo & Xiang-Fa Deng, 2017. "Sodium p -Aminosalicylic Acid Reverses Sub-Chronic Manganese-Induced Impairments of Spatial Learning and Memory Abilities in Rats, but Fails to Restore γ-Aminobutyric Acid Levels," IJERPH, MDPI, vol. 14(4), pages 1-15, April.
    • Handle: RePEc:gam:jijerp:v:14:y:2017:i:4:p:400-:d:95407
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    References listed on IDEAS

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    1. Gunnar F. Kwakye & Monica M.B. Paoliello & Somshuvra Mukhopadhyay & Aaron B. Bowman & Michael Aschner, 2015. "Manganese-Induced Parkinsonism and Parkinson’s Disease: Shared and Distinguishable Features," IJERPH, MDPI, vol. 12(7), pages 1-22, July.
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