Department of Psychiatry and Psychotherapy, RWTH University Aachen, Aachen, Germany.
World J Biol Psychiatry. 2011 Dec;12(8):588-97. doi: 10.3109/15622975.2010.526146. Epub 2010 Nov 15.
Mounting evidence shows that oxidative stress (OS) and the purine/adenosine system play a key role in the pathophysiology of schizophrenia. Lately, our group pointed out that not only antioxidants, but also the prooxidant system plays an important role in neuro-psychiatric disorders. Xanthine oxidase (XO) is an enzyme of special interest in this context, since it acts as a prooxidant, but its main product is a vastly important antioxidant, uric acid (UA). Furthermore, XO plays major part in the purine/adenosine metabolism, which has been hypothesised to play a role in schizophrenia as well.
We examined the activity of XO in the striato-cortico-limbic system of schizophrenic patients (SP) and controls using a commercially available activity assay.
We found decreased activity of XO in the occipital cortex and thalamus of patients with psychosis. Furthermore, XO shows a significant positive correlation with chlorpromazine equivalents in the putamen and the temporal cortex.
Nevertheless, our results might suggest a downregulation of cellular defence mechanisms in schizophrenia in several brain regions, which could account for neuronal alterations which have been described before. This demonstrates that more research is needed to fully understand the role of the complex enzyme XO in the pathophysiology of schizophrenia.
越来越多的证据表明，氧化应激（OS）和嘌呤/腺苷系统在精神分裂症的病理生理学中起着关键作用。最近，我们的研究小组指出，在神经精神疾病中不仅抗氧化剂，促氧化剂系统也起着重要作用。黄嘌呤氧化酶（XO）在这方面特别有趣，因为它既是一种促氧化剂，但其主要产物尿酸（UA）也是一种非常重要的抗氧化剂。此外，XO 在嘌呤/腺苷代谢中起主要作用，这一假说也被认为与精神分裂症有关。
我们使用商业上可获得的活性测定法，检查了精神分裂症患者（SP）和对照组纹状体-皮质-边缘系统中 XO 的活性。
我们发现精神分裂症患者的枕叶皮质和丘脑 XO 活性降低。此外，XO 在纹状体和颞叶皮质与氯丙嗪等效物呈显著正相关。
然而，我们的结果可能表明在几个脑区中细胞防御机制的下调，这可以解释以前描述的神经元改变。这表明需要进一步研究以充分了解复杂酶 XO 在精神分裂症病理生理学中的作用。
