Strydom Andre, Dickinson Mark J, Shende Simadevi, Pratico Domenico, Walker Zuzana
Department of Mental Health Sciences, RFUCMS, UCL, Hampstead Campus, Rowland Hill Street, London, NW3 2PF, UK.
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):76-80. doi: 10.1016/j.pnpbp.2008.10.006. Epub 2008 Oct 25.
We aimed to study the hypothesis that high levels of superoxide dismutase (SOD1), previously reported in Down syndrome, would be associated with poorer ability on cognitive tests. Compensatory rises in the activity of glutathione peroxidase (GPx) was expected to be associated with better ability, so that a high ratio between SOD1 and GPx was hypothesised to be the best predictor of poorer cognitive performance.
32 adults with Down syndrome between the ages of 18 and 45 years donated blood samples for SOD1 and GPx assays and urine for Isoprostane 8,12-iso-iPF(2alpha)-VI assay, a specific biomarker of lipid peroxidation in vivo. Informants rated functional ability and memory function for all participants, and those adults with DS that was able to, also completed psychometric assessments of language ability and memory.
Neither SOD1 nor GPx were related to the elevated markers of lipid peroxidation previously described in living adults with DS, and our hypothesis that an increased SOD1/GPx ratio would be correlated with worse performance on cognitive or functional measures was not supported. Contrary to our hypothesis, we found that low SOD1/GPx ratios were associated with worse memory ability, which remained after controlling for confounders such as sex, age or nutritional supplements.
The anti-oxidant system in DS is implicated in the cognitive phenotype associated with the chromosomal disorder, but the variations in the phenotype could result from several possible gene or gene product interactions. Much further research is required before it will be possible to counteract the oxidative stress associated with DS.
我们旨在研究一个假说,即先前报道的唐氏综合征患者体内高水平的超氧化物歧化酶(SOD1)与认知测试中的较差表现相关。预计谷胱甘肽过氧化物酶(GPx)活性的代偿性升高与较好的表现相关,因此推测SOD1与GPx的高比率是认知表现较差的最佳预测指标。
32名年龄在18至45岁之间的唐氏综合征成年患者捐献了血液样本用于SOD1和GPx检测,并捐献了尿液用于8,12-异前列腺素F2α-VI(Isoprostane 8,12-iso-iPF(2alpha)-VI)检测,这是体内脂质过氧化的一种特异性生物标志物。信息提供者对所有参与者的功能能力和记忆功能进行了评分,那些能够进行测试的唐氏综合征成年患者还完成了语言能力和记忆的心理测量评估。
SOD1和GPx均与先前描述的成年唐氏综合征患者体内脂质过氧化的升高标志物无关,并且我们关于SOD1/GPx比率升高与认知或功能测量中较差表现相关的假说未得到支持。与我们的假说相反,我们发现低SOD1/GPx比率与较差的记忆能力相关,在控制了性别、年龄或营养补充剂等混杂因素后这种相关性仍然存在。
唐氏综合征中的抗氧化系统与这种染色体疾病相关的认知表型有关,但表型的变化可能由几种可能的基因或基因产物相互作用导致。在能够对抗与唐氏综合征相关的氧化应激之前,还需要进行更多的研究。