Involvement of striatal lipid peroxidation and inhibition of calcium influx into brain slices in neurobehavioral alterations in a rat model of short-term oral exposure to manganese
Involvement of striatal lipid peroxidation and inhibition of calcium influx into brain slices in neurobehavioral alterations in a rat model of short-term oral exposure to manganese
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DOI：
10.1016/j.neuro.2008.08.004
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发表时间：
2008-11-01
期刊：
影响因子：
3.4
通讯作者：
Antunes Soares, Felix Alexandre
中科院分区：
文献类型：
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作者：
Avila, Daiana Silva;Gubert, Priscila;Antunes Soares, Felix Alexandre
锰是生物系统的必需元素，然而职业暴露于高水平的锰可导致神经退行性疾病，其特征在于过量的锰积累，特别是在基底神经节的星形胶质细胞中，并且症状非常类似于特发性帕金森病（PD）。本研究的目的是评估成年大鼠暴露30天，以10和25毫克/毫升的氯化锰在他们的饮用水中的行为和生化变化。氯化锰中毒大鼠表现出受损的运动活动相比，对照组动物。此外，脂质过氧化作用增加，δ-氨基乙酰丙酸酯酶（δ-ALA-D，一种对促氧化剂敏感的酶）活性受到抑制，纹状体切片中Ca-45（2+）内流减少，表明该脑区受到短期Mn暴露的显著影响。与此相反，锰暴露与特征性锥体外系效应无关，也没有改变蛋白质氧化，这表明纹状体损伤代表锰诱导损伤的早期阶段。此外，锰处理与体重增加减少相关，但肝肾功能无明显变化。总之，锰引起氧化应激增加和减少Ca-45（2+）流入纹状体，这可能与受损的运动活动，但不与口面运动障碍的发生。(c)2008年爱思唯尔公司All rights reserved.
Manganese is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorder, characterized by excessive Mn accumulation, especially in astrocytes of basal ganglia and symptoms closely resembling idiopathic Parkinson's disease (PD). The purpose of this study was to evaluate behavioral and biochemical alterations in adult rats exposed for 30 days to 10 and 25 mg/mL of MnCl2 in their drinking water. MnCl2 intoxicated rats showed impaired locomotor activity in comparison to control animals. Furthermore, lipid peroxidation were increased, delta-aminolevulinate dehydratase (delta-ALA-D, an enzyme sensitive to pro-oxidant situations) activity was inhibited and Ca-45(2+) influx into striatal slices was decreased in rats exposed to 25 mg/mL of Mn, indicating that this brain region was markedly affected by short-term Mn exposure. In contrast, Mn exposure was not associated with characteristic extrapyramidal effects and did not modify protein oxidation, suggesting that the striatal damage represents early stages of Mn-induced damage. In addition, treatment with Mn was associated with reduced body weight gain, but there were no discernible alterations in liver and kidney function. In conclusion, Mn caused increased oxidative stress and decreased Ca-45(2+) influx into the striatum, which are likely linked to impaired locomotor activity, but not with the occurrence of orofacial dyskinesia. (c) 2008 Elsevier Inc. All rights reserved.