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
| Autor: | Tanara V. Peres, Hai-Lan Luo, Xiao-Wei Huang, Sheng-Nan He, Guo-Dong Lu, Hao-Yang Meng, Shao-Jun Li, Chao-Yan Ou, Yueming Jiang, Xiang-Fa Deng, Yi-Ni Luo |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Health Toxicology and Mutagenesis Glutamate decarboxylase lcsh:Medicine Morris water navigation task 010501 environmental sciences 01 natural sciences GABA transporter 1 Rats Sprague-Dawley Random Allocation chemistry.chemical_compound 0302 clinical medicine Manganism gamma-Aminobutyric Acid education.field_of_study biology Chemistry Manganese Poisoning Aminosalicylic Acid Biochemistry basal ganglia γ-aminobutyric acid medicine.drug medicine.medical_specialty Aminosalicylic acid Population Spatial Learning Article Drug Administration Schedule gamma-Aminobutyric acid 03 medical and health sciences Memory Internal medicine medicine Animals education sodium para-aminosalicylate 0105 earth and related environmental sciences Manganese lcsh:R Public Health Environmental and Occupational Health Neurotoxicity medicine.disease sub-chronic manganese exposure spatial learning and memory ability Rats Endocrinology biology.protein 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Environmental Research and Public Health International Journal of Environmental Research and Public Health, Vol 14, Iss 4, p 400 (2017) International Journal of Environmental Research and Public Health; Volume 14; Issue 4; Pages: 400 |
| ISSN: | 1660-4601 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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