Evidence of oxidative stress in the neocortex in incidental Lewy body disease
Evidence of oxidative stress in the neocortex in incidental Lewy body disease
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DOI：
10.1097/01.jnen.0000179050.54522.5a
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发表时间：
2005-09-01
影响因子：
3.2
通讯作者：
Ferrer, I
中科院分区：
文献类型：
--
作者：
Dalfó, E;Portero-Otín, M;Ferrer, I
氧化应激在帕金森病（PD）的黑质中有很好的记录，但在路易体疾病的早期阶段，对其他结构（包括大脑皮层）中的氧化损伤，特别是脂氧化，晚期糖基化（AGE）和AGE受体（AGEs）知之甚少。本研究分析这些参数在额叶皮层（区8），杏仁核，黑质在选定的情况下，没有神经系统症状和神经病理学证实的偶发路易体病相关的变化，比较他们与健康的年龄匹配的个人。本研究的结果表明，在帕金森病神经病理学早期阶段的病例中，标记物丙二醛去赖氨酸（MDAL）和4-羟基壬烯赖氨酸（HNE）的脂氧化损伤增加，黑质、杏仁核和额叶皮质中AGE表达增加，黑质和额叶皮质中AGEs细胞表达增加和异质性。此外，杏仁核和额叶皮质中的高过氧化二十二碳六烯酸含量增加。这些变化与皮质中的α-突触核蛋白聚集无关，与路易体痴呆（DLB）病例中额叶皮质SDS可溶性组分中发现的聚集体形成对比。DLB和偶发性路易体病的异常模式不同。此外，虽然AGE和HNE在DLB中的表达增加，但在DLB的大脑皮层中没有发现HNE和MDAL加合物的总量增加。初步分析已经确定了2个蛋白质与脂氧化损伤，α-突触核蛋白和锰超氧化物歧化酶（SOD 2），在偶然路易体病皮层。这项研究表明，在未经治疗的早期帕金森病神经病理学病例中，额叶皮层脂肪酸谱异常，选择性脂氧化损伤增加，AGE和AGEs表达增加。这些发现进一步支持抗氧化疗法治疗PD以减少与氧化应激相关的皮质损伤。
Oxidative stress has been well documented in the substantia nigra in Parkinson disease (PD), but little is known about oxidative damage, particularly lipoxidation, advanced glycation (AGE), and AGE receptors (RAGE) in other structures, including the cerebral cortex, in early stages of diseases with Lewy bodies. The present study was undertaken to analyze these parameters in the frontal cortex (area 8), amygdala, and substantia nigra in selected cases with no neurologic symptoms and with neuropathologically verified incidental Lewy body disease-related changes, comparing them with healthy age-matched individuals. Results of the present study have shown mass spectrometric and immunologic evidences of increased lipoxidative damage by the markers malondialdehyde-lysine (MDAL) and 4-hydroxynonenallysine (HNE), increased expression of AGE in the substantia nigra, amygdala, and frontal cortex, and increased and heterogeneous RAGE cellular expression in the substantia nigra and frontal cortex in cases with early stages of parkinsonian neuropathology. In addition, increased content of the highly peroxidizable docosahexaenoic acid in the amygdala and frontal cortex. These changes were not associated to a-synuclein aggregation in cortex, contrasting with aggregates found in SDS-soluble fractions of frontal cortex in dementia with Lewy bodies (DLB) cases. The pattern of lipidic abnormalities differed in DLB and incidental Lewy body disease. Furthermore, although AGE and RAGE expression were raised in DLB, no increase in the total amount of HNE and MDAL adducts was found in the cerebral cortex in DLB. Preliminary analyses have identified 2 proteins with lipoxidative damage, alpha-synuclein and manganese superoxide dismutase (SOD2), in incidentally Lewy body disease cortex. This study demonstrates abnormal fatty acid profiles, increased and selective lipoxidative damage, and increased AGE and RAGE expression in the frontal cortex in cases with early stages of parkinsonian neuropathology without treatment. These findings further support antioxidant therapy in the treatment of PD to reduce cortical damage associated with oxidative stress.