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L-Tyrosine administration increases acetylcholinesterase activity in rats

机译:L-酪氨酸给药可增加大鼠的乙酰胆碱酯酶活性

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Tyrosinemia is a rare genetic disease caused by mutations on genes that codify enzymes responsible for tyrosine metabolism. Considering that tyrosinemics patients usually present symptoms associated with central nervous system alterations that ranges from slight decreases in intelligence to severe mental retardation, we decided to investigate whether acute and chronic administration of l-tyrosine in rats would affect acetylcholinesterase mRNA expression and enzymatic activity during their development. In our acute protocol, Wistar rats (10 and 30 days old) were killed one hour after a single intraperitoneal l-tyrosine injection (500 mg/kg) or saline. Chronic administration consisted of l-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old) and rats were killed 12 h after last injection. Acetylcholinesterase activity was measured by Ellman's method and acetylcholinesterase expression was carried out by a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay. We observed that acute (10 and 30 days old rats) and chronic l-tyrosine administration increased acetylcholinesterase activity in serum and all tested brain areas (hippocampus, striatum and cerebral cortex) when compared to control group. Moreover, there was a significant decrease in mRNA levels of acetylcholinesterase in hippocampus was observed after acute protocol (10 and 30 days old rats) and in striatum after chronic protocol. In case these alterations also occur in the brain of the patients, our results may explain, at least in part, the neurological sequelae associated with high plasma concentrations of tyrosine seen in patients affected by tyrosinemia type II.
机译:酪氨酸血症是一种罕见的遗传病,由编码致酪氨酸代谢酶的基因突变引起。考虑到酪氨酸血症患者通常表现出与中枢神经系统改变有关的症状,包括从智力的轻度下降到严重的智力低下,我们决定调查在大鼠的急性和慢性给予l-酪氨酸是否会影响其过程中乙酰胆碱酯酶mRNA的表达和酶活性。发展。在我们的急性方案中,Wistar大鼠(10和30天大)在一次腹膜内注射I-酪氨酸(500 mg / kg)或生理盐水一小时后被处死。在Wistar大鼠(7天大)中,长期服用l-酪氨酸(500 mg / kg)或盐水,每12小时注射一次,持续24天,最后一次注射12小时后处死大鼠。通过Ellman方法测定乙酰胆碱酯酶活性,并且通过半定量逆转录酶聚合酶链反应(RT-PCR)测定法进行乙酰胆碱酯酶的表达。我们观察到,与对照组相比,急性(10和30天大的大鼠)和长期施用L-酪氨酸可提高血清和所有测试的大脑区域(海马,纹状体和大脑皮层)的乙酰胆碱酯酶活性。此外,急性方案(10和30天大的大鼠)后和慢性方案后纹状体中的海马中乙酰胆碱酯酶的mRNA水平均显着降低。如果这些变化也发生在患者的大脑中,我们的结果至少可以部分解释在II型酪氨酸血症患者中与高血浆酪氨酸浓度相关的神经后遗症。

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