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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

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Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
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Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China
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Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, China
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Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning 530021, China
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Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer, 209, 1300 Morris Park Ave, Bronx, NY 10461, USA
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Department of Anatomy, School of Pre-Clinical Medicine, Guangxi Medical University, Nanning 530021, China
*
Author to whom correspondence should be addressed.
Shao-Jun Li, Chao-Yan Ou, Sheng-Nan He and Xiao-Wei Huang contributed equally to this article.
Academic Editor: William Toscano
Int. J. Environ. Res. Public Health 2017, 14(4), 400; https://doi.org/10.3390/ijerph14040400
Received: 12 December 2016 / Revised: 22 March 2017 / Accepted: 23 March 2017 / Published: 10 April 2017
(This article belongs to the Section Global Health)
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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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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