title: 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.
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.
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China. lishaojun0613@163.com.
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China. oak009@163.com.|Department of Toxicology, School of Public Health, Guilin Medical University, Guilin 541004, China. oak009@163.com.
authors.forename: Chao-Yan
authors.initials: CY
authors.lastname: Ou
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China. qiqishengnh@sina.com.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: He
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China. xwhuang82@163.com.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Huang
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China. fanxingddlx@163.com.
authors.forename: Hai-Lan
authors.initials: HL
authors.lastname: Luo
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China. moso_17@163.com.
authors.forename: Hao-Yang
authors.initials: HY
authors.lastname: Meng
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China. golden_lu@hotmail.com.|Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning 530021, China. golden_lu@hotmail.com.|Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning 530021, China. golden_lu@hotmail.com.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Lu
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China. ymjianggxmu@163.com.
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Jiang
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer, 209, 1300 Morris Park Ave, Bronx, NY 10461, USA. Tanara.Peres-Vieira@einstein.yu.edu.
authors.forename: Tanara
authors.initials: T
authors.lastname: Vieira Peres
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China. ninimimimomo@126.com.
authors.forename: Yi-Ni
authors.initials: YN
authors.lastname: Luo
authors.affiliation: Department of Anatomy, School of Pre-Clinical Medicine, Guangxi Medical University, Nanning 530021, China. dengxfa@163.com.
authors.forename: Xiang-Fa
authors.initials: XF
authors.lastname: Deng
mesh_terms: D010131:Aminosalicylic Acid / Q000494:pharmacology*; D000818:Animals; D004334:Drug Administration Schedule; D008297:Male; D008345:Manganese / Q000633:toxicity*; D020149:Manganese Poisoning / Q000473:pathology*; D008568:Memory / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000097:blood* / Q000378:metabolism
chemical_list: D008345:Manganese; D005680:gamma-Aminobutyric Acid; D010131:Aminosalicylic Acid
keywords: basal ganglia; sodium para-aminosalicylate; spatial learning and memory ability; sub-chronic manganese exposure; γ-aminobutyric acid