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
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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