【文题】Low brain glutathione and ascorbic acid associated with dopamine uptake inhibition during rat's development induce long-term cognitive deficit: relevance to schizophrenia.
【杂志】Neurobiol Dis. 2004 Feb;15(1):93-105.
【作者】Castagne V, Rougemont M, Cuenod M, Do KQ.
【单位】Center for Research in Psychiatric Neuroscience, Department of Adult Psychiatry, Lausanne University-CHUV, CH-1008 Prilly, Lausanne, Switzerland. vincent.casagne@inst.hospvd.ch
【文摘】Schizophrenia is associated with a cerebral glutathione deficit, which may leave the brain susceptible to oxidants. To study the consequences of a glutathione deficit, we treated developing rats with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione synthesis, and later investigated their behaviour until adulthood. Since rodents may in some occasions compensate for a glutathione deficit by ascorbic acid (AA), we used Osteogenic Disorder Shionogi (ODS) mutant rats, which like humans, cannot synthetize ascorbic acid. Moreover, as hyperactivity of the dopaminergic system may be associated with schizophrenia, some rats were treated with the dopamine uptake inhibitor GBR 12909. Whereas ODS rats treated with either BSO or GBR 12909 alone had normal behaviour, rats treated with both BSO and GBR 12909 failed to discriminate between familiar and novel objects although other behaviours proved to be normal. In contrast, nonmutant rats were not affected by treatment with BSO and GBR 12909. Our results suggest that low brain glutathione and ascorbic acid levels associated with a perturbation of the dopaminergic system actively participate in the development of some cognitive deficits affecting schizophrenic patients.
【翻译】精神分裂症与脑内谷胱苷肽缺失有关，它导致脑易于氧化。为了研究谷胱苷肽缺失的影响，我们给大鼠L-亚矾胺-(S,R)-丁硫氨酸(BSO)—谷胱苷肽合成的抑制剂，然后研究其行为改变直至成年。由于嗫齿类动物有时候能通过抗坏血酸（AA）代偿谷胱苷肽的缺失，所以我们使用和人类一样不能合成抗坏血酸的ODS突变大鼠。而且，由于多巴胺系统高活性与精神分裂症有关，所以部分大鼠给多巴胺摄取抑制剂 GBR 12909。ODS大鼠单独给 BSO 或 GBR12909 行为活动正常，同时给BSO 和 GBR 12909 的大鼠虽然其他行为正常但不能区分熟悉的和陌生的物体。相比之下，BSO 和 GBR 12909.对非突变大鼠没有影响。我们的结果表明脑内低谷胱肝肽和抗坏血酸水平以及对多巴胺系统的干扰能参与精神分裂症认知缺陷的形成和发展。
转自 ziyu00
