Sedlak Thomas W, Nucifora Leslie G, Koga Minori, Shaffer Lindsay S, Higgs Cecilia, Tanaka Teppei, Wang Anna M, Coughlin Jennifer M, Barker Peter B, Fahey Jed W, Sawa Akira
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Radiology and Radiological Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mol Neuropsychiatry. 2018 May;3(4):214-222. doi: 10.1159/000487639. Epub 2018 Apr 17.
Schizophrenia and other neuropsychiatric disorders await mechanism-associated interventions. Excess oxidative stress is increasingly appreciated to participate in the pathophysiology of brain disorders, and decreases in the major antioxidant, glutathione (GSH), have been reported in multiple studies. Technical cautions regarding the estimation of oxidative stress-related changes in the brain via imaging techniques have led investigators to explore peripheral GSH as a possible pathological signature of oxidative stress-associated brain changes. In a preclinical model of GSH deficiency, we found a correlation between whole brain and peripheral GSH levels. We found that the naturally occurring isothiocyanate sulforaphane increased blood GSH levels in healthy human subjects following 7 days of daily oral administration. In parallel, we explored the potential influence of sulforaphane on brain GSH levels in the anterior cingulate cortex, hippocampus, and thalamus via 7-T magnetic resonance spectroscopy. A significant positive correlation between blood and thalamic GSH post- and pre-sulforaphane treatment ratios was observed, in addition to a consistent increase in brain GSH levels in response to treatment. This clinical pilot study suggests the value of exploring relationships between peripheral GSH and clinical/neuropsychological measures, as well as the influences sulforaphane has on functional measures that are altered in neuropsychiatric disorders.
精神分裂症和其他神经精神疾病仍有待机制相关的干预措施。越来越多的研究认识到氧化应激过度参与脑部疾病的病理生理过程，多项研究报告称主要抗氧化剂谷胱甘肽（GSH）水平下降。由于通过成像技术评估大脑中氧化应激相关变化存在技术限制，研究人员开始探索外周GSH作为氧化应激相关脑部变化的可能病理特征。在一个GSH缺乏的临床前模型中，我们发现全脑和外周GSH水平之间存在相关性。我们发现，天然存在的异硫氰酸酯萝卜硫素在健康人类受试者中每日口服7天后可提高血液GSH水平。同时，我们通过7-T磁共振波谱探索了萝卜硫素对前扣带回皮质、海马体和丘脑的脑GSH水平的潜在影响。除了治疗后脑GSH水平持续升高外，还观察到血液和丘脑GSH治疗前后比值之间存在显著正相关。这项临床初步研究表明，探索外周GSH与临床/神经心理学指标之间的关系，以及萝卜硫素对神经精神疾病中改变的功能指标的影响具有重要价值。
