Mazzola Priscila Nicolao, Bruinenberg Vibeke, Anjema Karen, van Vliet Danique, Dutra-Filho Carlos Severo, van Spronsen Francjan J, van der Zee Eddy A
Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES) - University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
JIMD Rep. 2016;27:69-77. doi: 10.1007/8904_2015_498. Epub 2015 Oct 7.
High phenylalanine levels in phenylketonuria (PKU) have been associated with brain oxidative stress and amino acid imbalance. Exercise has been shown to improve brain function in hyperphenylalaninemia and neurodegenerative diseases. This study aimed to verify the effects of exercise on coordination and balance, plasma and brain amino acid levels, and brain oxidative stress markers in PKU mice.
Twenty wild-type (WT) and 20 PAH(enu2) (PKU) C57BL/6 mice were placed in cages with (exercise, Exe) or without (sedentary, Sed) running wheels during 53 days. At day 43, a balance beam test was performed. Plasma and brain were collected for analyses of amino acid levels and the oxidative stress parameters superoxide dismutase (SOD) activity, sulfhydryl and reduced glutathione (GSH) contents, total radical-trapping antioxidant potential (TRAP), and total antioxidant reactivity (TAR).
SedPKU showed poor coordination (p < 0.001) and balance (p < 0.001), higher plasma and brain phenylalanine (p < 0.001), and increased brain oxidative stress (p < 0.05) in comparison to SedWT. ExePKU animals ran less than ExeWT (p = 0.018). Although no improvement was seen in motor coordination and balance, exercise in PKU restored SOD, sulfhydryl content, and TRAP levels to controls. TAR levels were increased in ExePKU in comparison to SedPKU (p = 0.012). Exercise decreased plasma and brain glucogenic amino acids in ExePKU, but did not change plasma and brain phenylalanine in both WT and PKU.
Exercise prevents oxidative stress in the brain of PKU mice without modifying phenylalanine levels. Hence, exercise positively affects the brain, demonstrating its value as an intervention to improve brain quality in PKU.
苯丙酮尿症（PKU）患者体内高苯丙氨酸水平与脑氧化应激及氨基酸失衡有关。运动已被证明可改善高苯丙氨酸血症和神经退行性疾病患者的脑功能。本研究旨在验证运动对PKU小鼠的协调能力、平衡能力、血浆及脑内氨基酸水平以及脑氧化应激标志物的影响。
将20只野生型（WT）和20只PAH(enu2)（PKU）C57BL/6小鼠置于带有（运动组，Exe）或不带有（久坐组，Sed）跑轮的笼子中，持续53天。在第43天，进行平衡木试验。采集血浆和脑样本，用于分析氨基酸水平以及氧化应激参数超氧化物歧化酶（SOD）活性、巯基和还原型谷胱甘肽（GSH）含量、总自由基捕获抗氧化能力（TRAP）和总抗氧化反应性（TAR）。
与久坐的野生型小鼠（SedWT）相比，久坐的PKU小鼠（SedPKU）表现出较差的协调能力（p < 0.001）和平衡能力（p < 0.001），血浆和脑内苯丙氨酸水平更高（p < 0.001），脑氧化应激增加（p < 0.05）。运动的PKU小鼠（ExePKU）比运动的野生型小鼠（ExeWT）跑动更少（p = 0.018）。虽然运动在运动协调性和平衡能力方面未显示出改善，但PKU小鼠的运动使SOD、巯基含量和TRAP水平恢复至对照组水平。与久坐的PKU小鼠相比，运动的PKU小鼠的TAR水平升高（p = 0.012）。运动降低了运动的PKU小鼠血浆和脑内的生糖氨基酸，但在野生型和PKU小鼠中均未改变血浆和脑内的苯丙氨酸水平。
运动可预防PKU小鼠脑内的氧化应激，而不改变苯丙氨酸水平。因此，运动对脑有积极影响，证明其作为改善PKU患者脑质量的干预措施的价值。
