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
Autor: | Chao-Yan Ou, Yi-Ni Luo, Hai-Lan Luo, Yueming Jiang, Sheng-Nan He, Shao-Jun Li, Zong-Xiang Yuan, Yu-Huan Mo, Xiang-Fa Deng, Hao-Yang Meng |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine GABA Plasma Membrane Transport Proteins medicine.medical_specialty Neuropil Time Factors Endocrinology Diabetes and Metabolism Blotting Western Clinical Biochemistry Gene Expression Glutamic Acid Biochemistry Aminobutyric acid Basal Ganglia GABA transporter 1 Muscle hypertrophy Rats Sprague-Dawley Inorganic Chemistry 03 medical and health sciences 0302 clinical medicine Microscopy Electron Transmission Memory Internal medicine Basal ganglia medicine Animals Maze Learning gamma-Aminobutyric Acid Neurons Manganese biology Reverse Transcriptase Polymerase Chain Reaction GABAA receptor Biochemistry (medical) Neurotoxicity General Medicine Metabolism medicine.disease Aminosalicylic Acid 030104 developmental biology Endocrinology medicine.anatomical_structure Astrocytes biology.protein 030217 neurology & neurosurgery |
Zdroj: | Biological Trace Element Research. 176:143-153 |
ISSN: | 1559-0720 0163-4984 |
Popis: | 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. |
Databáze: | OpenAIRE |
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