Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Mol Neurobiol. 2017 Dec;54(10):7796-7807. doi: 10.1007/s12035-016-0289-1. Epub 2016 Nov 14.
The study of the long-term neurological consequences of early exposure with methylphenidate (MPH) is very important since this psychostimulant has been widely misused by children and adolescents who do not meet full diagnostic criteria for ADHD. The aim of this study was to examine the effect of early chronic exposure with MPH on amino acids profile, glutamatergic and Na,K-ATPase homeostasis, as well as redox and energy status in the hippocampus of juvenile rats. Wistar male rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 45th day of age. Results showed that MPH altered amino acid profile in the hippocampus, decreasing glutamine levels. Glutamate uptake and Na,K-ATPase activity were decreased after chronic MPH exposure in the hippocampus of rats. No changes were observed in the immunocontents of glutamate transporters (GLAST and GLT-1), and catalytic subunits of Na,K-ATPase (α, α, and α), as well as redox status. Moreover, MPH provoked a decrease in ATP levels in the hippocampus of chronically exposed rats, while citrate synthase, succinate dehydrogenase, respiratory chain complexes activities (II, II-III, and IV), as well as mitochondrial mass and mitochondrial membrane potential were not altered. Taken together, our results suggest that chronic MPH exposure at early age impairs glutamate uptake and Na,K-ATPase activity probably by decreasing in ATP levels observed in rat hippocampus.
研究早期接触哌醋甲酯（MPH）对神经的长期影响非常重要，因为这种精神兴奋剂已被广泛滥用，许多儿童和青少年并不符合 ADHD 的全部诊断标准。本研究旨在研究早期慢性暴露于 MPH 对幼年大鼠海马中氨基酸谱、谷氨酸能和 Na，K-ATP 酶稳态、氧化还原和能量状态的影响。雄性 Wistar 大鼠从第 15 天到第 45 天每天接受腹腔注射 MPH（2.0mg/kg）或生理盐水（对照）。结果表明，MPH 改变了海马中的氨基酸谱，降低了谷氨酰胺水平。慢性 MPH 暴露后，大鼠海马中的谷氨酸摄取和 Na，K-ATP 酶活性降低。谷氨酸转运体（GLAST 和 GLT-1）和 Na，K-ATP 酶催化亚基（α、α 和 α）的免疫含量以及氧化还原状态没有变化。此外，MPH 导致慢性暴露大鼠海马中 ATP 水平降低，而柠檬酸合酶、琥珀酸脱氢酶、呼吸链复合物活性（II、II-III 和 IV）以及线粒体质量和线粒体膜电位没有改变。总之，我们的结果表明，幼年时慢性 MPH 暴露会损害谷氨酸摄取和 Na，K-ATP 酶活性，可能是通过降低大鼠海马中观察到的 ATP 水平。
