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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

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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, GABAA mRNA and GABAA protein expression through decreasing GABA transporter 1(GAT-1) and GABA A receptor (GABAA) mRNA expression, and increasing GABAA protein 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.

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    1. Department of Toxicology, School of Public Health, Guangxi Medical University, 22 Shuang-yong Rd, Nanning, Guangxi, 530021, China

      Chao-Yan Ou, Yi-Ni Luo, Sheng-Nan He, Hai-Lan Luo, Zong-Xiang Yuan, Hao-Yang Meng, Yu-Huan Mo, Shao-Jun Li & Yue-Ming Jiang

    2. Department of Toxicology, School of Public Health, Guilin Medical University, Guilin, 541004, China

      Chao-Yan Ou

    3. Department of Anatomy, School of Pre-clinical Medicine, Guangxi Medical University, Nanning, 530021, China

      Xiang-Fa Deng

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    This study was supported by grants from the National Natural Science Foundation of China (NSFC 81072320, 81460505, 30760210), Guangxi Natural Science Foundation (GXNSFAA 118232, 2015GXNSFAA139181) and the Innovation Project of Guangxi Graduate Education.

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    Drs. Chao-Yan Ou, Yi-Ni Luo, Sheng-Nan He and Xiang-Fa Deng contributed equally to this article.

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    Ou, CY., Luo, YN., He, SN. et al. 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. Biol Trace Elem Res 176, 143–153 (2017). https://doi.org/10.1007/s12011-016-0802-4

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