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

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 and Xiang-Fa Deng
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Shao-Jun Li: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
Chao-Yan Ou: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
Sheng-Nan He: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
Xiao-Wei Huang: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
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
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

IJERPH, 2017, vol. 14, issue 4, 1-15

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 ?-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.

Keywords: sodium para-aminosalicylate; sub-chronic manganese exposure; spatial learning and memory ability; ?-aminobutyric acid; basal ganglia (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2017
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