title: Sodium P-Aminosalicylic Acid Improved Manganese-Induced Learning and Memory Dysfunction via Restoring the Ultrastructural Alterations and γ-Aminobutyric Acid Metabolism Imbalance in the Basal Ganglia.
abstract: Excessive intake of manganese (Mn) may cause neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has been used successfully in the treatment of Mn-induced neurotoxicity. The γ-aminobutyric acid (GABA) is related with learning and memory abilities. However, the mechanism of PAS-Na on improving Mn-induced behavioral deficits is unclear. The current study was aimed to investigate the effects of PAS-Na on Mn-induced behavioral deficits and the involvement of ultrastructural alterations and γ-aminobutyric acid (GABA) metabolism in the basal ganglia of rats. Sprague-Dawley rats received daily intraperitoneally injections of 15 mg/kg MnCl2.4H2O, 5d/week for 4 weeks, followed by a daily back subcutaneously (sc.) dose of PAS-Na (100 and 200 mg/kg), 5 days/week for another 3 or 6 weeks. Mn exposure for 4 weeks and then ceased Mn exposure for 3 or 6 weeks impaired spatial learning and memory abilities, and these effects were long-lasting. Moreover, Mn exposure caused ultrastructural alterations in the basal ganglia expressed as swollen neuronal with increasing the electron density in the protrusions structure and fuzzed the interval of neuropil, together with swollen, focal hyperplasia, and hypertrophy of astrocytes. Additionally, the results also indicated that Mn exposure increased Glu/GABA values as by feedback loops controlling GAT-1, GABAAmRNA and GABAAprotein expression through decreasing GABA transporter 1(GAT-1) and GABA A receptor (GABAA) mRNA expression, and increasing GABAAprotein expression in the basal ganglia. But Mn exposure had no effects on GAT-1 protein expression. PAS-Na treatment for 3 or 6 weeks effectively restored the above-mentioned adverse effects induced by Mn. In conclusion, these findings suggest the involvement of GABA metabolism and ultrastructural alterations of basal ganglia in PAS-Na's protective effects on the spatial learning and memory abilities.
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, 22 Shuang-yong Rd, Nanning, Guangxi, 530021, China.|Department of Toxicology, School of Public Health, Guilin Medical University, Guilin, 541004, China.
authors.forename: Chao-Yan
authors.initials: CY
authors.lastname: Ou
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, 22 Shuang-yong Rd, Nanning, Guangxi, 530021, China.
authors.forename: Yi-Ni
authors.initials: YN
authors.lastname: Luo
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, 22 Shuang-yong Rd, Nanning, Guangxi, 530021, China.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: He
authors.affiliation: Department of Anatomy, School of Pre-clinical Medicine, Guangxi Medical University, Nanning, 530021, China.
authors.forename: Xiang-Fa
authors.initials: XF
authors.lastname: Deng
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, 22 Shuang-yong Rd, Nanning, Guangxi, 530021, China.
authors.forename: Hai-Lan
authors.initials: HL
authors.lastname: Luo
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, 22 Shuang-yong Rd, Nanning, Guangxi, 530021, China.
authors.forename: Zong-Xiang
authors.initials: ZX
authors.lastname: Yuan
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, 22 Shuang-yong Rd, Nanning, Guangxi, 530021, China.
authors.forename: Hao-Yang
authors.initials: HY
authors.lastname: Meng
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, 22 Shuang-yong Rd, Nanning, Guangxi, 530021, China.
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Mo
authors.affiliation: Department of Toxicology, School of Public Health, Guangxi Medical University, 22 Shuang-yong Rd, Nanning, Guangxi, 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, 22 Shuang-yong Rd, Nanning, Guangxi, 530021, China. ymjianggxmu@163.com.
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Jiang
mesh_terms: D010131:Aminosalicylic Acid / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D015153:Blotting, Western; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019581:Neuropil / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; C493415:Slc6a1 protein, rat; D018698:Glutamic Acid; D008345:Manganese; D005680:gamma-Aminobutyric Acid; D010131:Aminosalicylic Acid
keywords: Manganese; Sodium para-aminosalicylic acid; Spatial learning-memory ability impairment; Ultrastructural alterations of basal ganglia; γ-aminobutyric acid (GABA) metabolism