Neuroscience Research Australia, Sydney, New South Wales, Australia.
PLoS One. 2011 Feb 28;6(2):e17299. doi: 10.1371/journal.pone.0017299.
We present a lipidomics analysis of human Parkinson's disease tissues. We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra.
METHODOLOGY/PRINCIPAL FINDINGS: Using liquid chromatography mass spectrometry lipidomics techniques for an initial screen of 200 lipid species, significant changes in 79 sphingolipid, glycerophospholipid and cholesterol species were detected in the visual cortex of Parkinson's disease patients (n = 10) compared to controls (n = 10) as assessed by two-sided unpaired t-test (p-value <0.05). False discovery rate analysis confirmed that 73 of these 79 lipid species were significantly changed in the visual cortex (q-value <0.05). By contrast, changes in 17 and 12 lipid species were identified in the Parkinson's disease amygdala and anterior cingulate cortex, respectively, compared to controls; none of which remained significant after false discovery rate analysis. Using gas chromatography mass spectrometry techniques, 6 out of 7 oxysterols analysed from both non-enzymatic and enzymatic pathways were also selectively increased in the Parkinson's disease visual cortex. Many of these changes in visual cortex lipids were correlated with relevant changes in the expression of genes involved in lipid metabolism and an oxidative stress response as determined by quantitative polymerase chain reaction techniques.
CONCLUSIONS/SIGNIFICANCE: The data indicate that changes in lipid metabolism occur in the Parkinson's disease visual cortex in the absence of obvious pathology. This suggests that normalization of lipid metabolism and/or oxidative stress status in the visual cortex may represent a novel route for treatment of non-motor symptoms, such as visual hallucinations, that are experienced by a majority of Parkinson's disease patients.
我们对人类帕金森病组织进行了脂质组学分析。我们主要关注初级视觉皮层，这是一个没有发生病变和路易体的区域；另外两个区域是杏仁核和前扣带皮层，它们在不同的疾病阶段含有路易体，但没有黑质那样严重的退化。
方法/主要发现：使用液相色谱-质谱脂质组学技术对 200 种脂质进行初步筛选，通过双侧非配对 t 检验（p 值 <0.05）发现帕金森病患者（n = 10）与对照组（n = 10）相比，视觉皮层中有 79 种鞘脂、甘油磷脂和胆固醇发生了显著变化。错误发现率分析证实，这 79 种脂质中有 73 种在视觉皮层中发生了显著变化（q 值 <0.05）。相比之下，与对照组相比，帕金森病患者的杏仁核和前扣带皮层分别有 17 种和 12 种脂质发生了变化；经过错误发现率分析后，这些变化都没有显著意义。使用气相色谱-质谱技术，对非酶和酶促途径分析的 7 种氧化固醇中的 6 种也发现选择性地增加了帕金森病患者的视觉皮层。许多视觉皮层脂质的变化与定量聚合酶链反应技术确定的脂质代谢和氧化应激反应相关基因的表达变化相关。
结论/意义：这些数据表明，脂质代谢的变化发生在帕金森病患者的视觉皮层中，而没有明显的病理变化。这表明，在视觉皮层中正常化脂质代谢和/或氧化应激状态可能代表一种治疗非运动症状（如帕金森病患者大多数人经历的视觉幻觉）的新途径。
