Vernon Anthony C, So Po-Wah, Lythgoe David J, Chege Winfred, Cooper Jonathan D, Williams Steven C R, Kapur Shitij
King's College London, Institute of Psychiatry Psychology and Neuroscience, Department of Psychosis Studies, De Crespigny Park, London SE5 8AF, UK.
King's College London, Institute of Psychiatry, Department of Neuroimaging, Centre for Neuroimaging Sciences, De Crespigny Park, London SE5 8AF, UK.
Eur Neuropsychopharmacol. 2015 Dec;25(12):2210-20. doi: 10.1016/j.euroneuro.2015.09.022. Epub 2015 Oct 21.
Proton magnetic resonance spectroscopy ((1)H MRS) studies in schizophrenia patients generally report decreased levels of N-acetyl-aspartate (NAA), glutamate and glutathione, particularly in frontal cortex. However, these data are inconsistent in part due to confounds associated with clinical samples. The lack of validated diagnostic biomarkers also hampers analysis of the neurodevelopmental trajectory of neurochemical abnormalities. Rodent models are powerful tools to address these issues, particularly when combined with (1)H MRS (clinically comparable technology). We investigated the trajectory of metabolic changes in the prefrontal cortex during brain maturation from adolescence to adulthood in vivo using (1)H MRS in rats exposed prenatally to polyinosinic-polycytidylic acid (POL), a rodent model of maternal immune activation (MIA), an epidemiological risk factor for several psychiatric disorders with a neurodevelopmental origin. Longitudinal in vivo (1)H MRS revealed a significant decrease in PFC levels of GSH and taurine in adult, but not adolescent rats. Significant age×MIA interactions for PFC levels of NAA were also observed. These data replicate some deficits observed in the PFC of patients with schizophrenia. There were no significant changes in the levels of glutamate or any other metabolite. These data suggest prenatal exposure to POL leads to subtle metabolic perturbations of the normal maturing PFC, which may be related to subsequent behavioural abnormalities. Further work is however required to examine any potential confound of shipping stress on the presumed imbalances in PFC metabolites in POL-exposed offspring. Testing the interactions between MIA with stress or genetic risk variants will also be an important advance.
对精神分裂症患者进行的质子磁共振波谱（¹H MRS）研究通常报告称，N-乙酰天门冬氨酸（NAA）、谷氨酸和谷胱甘肽水平降低，尤其是在额叶皮质。然而，这些数据并不一致，部分原因是与临床样本相关的混杂因素。缺乏经过验证的诊断生物标志物也阻碍了对神经化学异常神经发育轨迹的分析。啮齿动物模型是解决这些问题的有力工具，特别是与¹H MRS（临床可比技术）结合使用时。我们使用¹H MRS对产前暴露于聚肌苷酸-聚胞苷酸（POL）的大鼠进行体内研究，调查了从青春期到成年期大脑成熟过程中前额叶皮质代谢变化的轨迹。POL是一种母体免疫激活（MIA）的啮齿动物模型，MIA是几种具有神经发育起源的精神疾病的流行病学危险因素。纵向体内¹H MRS显示，成年大鼠而非青春期大鼠的前额叶皮质中谷胱甘肽和牛磺酸水平显著降低。还观察到前额叶皮质中NAA水平存在显著的年龄×MIA交互作用。这些数据重现了精神分裂症患者前额叶皮质中观察到的一些缺陷。谷氨酸或任何其他代谢物的水平没有显著变化。这些数据表明，产前暴露于POL会导致正常成熟的前额叶皮质出现细微的代谢紊乱，这可能与随后的行为异常有关。然而，还需要进一步的研究来检查运输应激对POL暴露后代前额叶皮质代谢物假定失衡的任何潜在混杂影响。测试MIA与应激或遗传风险变异之间的相互作用也将是一个重要的进展。
