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Int. J. Environ. Res. Public Health 2017, 14(4), 400; doi:10.3390/ijerph14040400

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

1
Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
2
Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China
3
Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, China
4
Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning 530021, China
5
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer, 209, 1300 Morris Park Ave, Bronx, NY 10461, USA
6
Department of Anatomy, School of Pre-Clinical Medicine, Guangxi Medical University, Nanning 530021, China
Shao-Jun Li, Chao-Yan Ou, Sheng-Nan He and Xiao-Wei Huang contributed equally to this article.
*
Author to whom correspondence should be addressed.
Academic Editor: William Toscano
Received: 12 December 2016 / Revised: 22 March 2017 / Accepted: 23 March 2017 / Published: 10 April 2017
(This article belongs to the Section Global Health)
View Full-Text   |   Download PDF [4393 KB, uploaded 10 April 2017]   |  

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 MnCl2 (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 (GABAA) 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. View Full-Text
Keywords: sodium para-aminosalicylate; sub-chronic manganese exposure; spatial learning and memory ability; γ-aminobutyric acid; basal ganglia sodium para-aminosalicylate; sub-chronic manganese exposure; spatial learning and memory ability; γ-aminobutyric acid; basal ganglia
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, S.-J.; Ou, C.-Y.; He, S.-N.; Huang, X.-W.; Luo, H.-L.; Meng, H.-Y.; Lu, G.-D.; Jiang, Y.-M.; Vieira Peres, T.; Luo, Y.-N.; Deng, X.-F. 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. Int. J. Environ. Res. Public Health 2017, 14, 400.

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