Loeffler D A, Sima A A, LeWitt P A
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Free Radic Res. 2001 Aug;35(2):111-8. doi: 10.1080/10715760100300651.
Ceruloplasmin (CP) is a 132 kd cuproprotein which, together with transferrin, provides the majority of anti-oxidant capacity in serum. Increased iron deposition and lipid peroxidation in the basal ganglia of subjects with hereditary CP deficiency suggest that CP may serve as an anti-oxidant in the brain as well. The present study compared CP immunoreactivity in brain specimens from normal controls and subjects with neurodegenerative disorders (Alzheimer's disease [AD], Parkinson's disease [PD], progressive supranuclear palsy [PSP], and Huntington's disease [HD]) (n = 5 per group). The relative intensity of neuronal CP staining and the numbers of CP-stained neurons per 25x microscope field were determined in hippocampus (CA1, subiculum, and parahippocampal gyrus), parietal cortex, frontal cortex, substantia nigra, and caudate. CP was detected in both neurons and astrocytes in all specimens, and in senile plaques and occasional neurofibrillary tangles in AD brain. Neuronal CP staining intensity tended to increase in most AD brain regions, but was statistically significant vs controls only in the CA1 region of hippocampus (p = .016). Neuronal CP staining in brain specimens from other neurodegenerative disorders showed a slight but nonsignificant increase vs controls. The numbers of CP-stained neurons per field did not differ between the various neurodegenerative disorders and controls. These results suggest that a modest increase in neuronal CP content is present in the AD brain, and lesser elevations in neuronal CP occur in the other neurodegenerative disorders in this study. Though CP functions as both an acute phase protein and an anti-oxidant in peripheral tissues, whether it does so in the brain remains to be determined.
铜蓝蛋白(CP)是一种132kd的铜蛋白,它与转铁蛋白一起提供了血清中大部分的抗氧化能力。遗传性CP缺乏患者基底神经节中铁沉积增加和脂质过氧化表明,CP在大脑中可能也起到抗氧化剂的作用。本研究比较了正常对照和患有神经退行性疾病(阿尔茨海默病[AD]、帕金森病[PD]、进行性核上性麻痹[PSP]和亨廷顿病[HD])患者(每组n = 5)脑标本中的CP免疫反应性。在海马体(CA1、海马下托和海马旁回)、顶叶皮质、额叶皮质、黑质和尾状核中,测定神经元CP染色的相对强度以及每25倍显微镜视野中CP染色神经元的数量。在所有标本的神经元和星形胶质细胞中均检测到CP,在AD脑中的老年斑和偶尔的神经原纤维缠结中也检测到CP。大多数AD脑区的神经元CP染色强度有增加趋势,但仅在海马体的CA1区与对照组相比有统计学意义(p = 0.016)。来自其他神经退行性疾病脑标本中的神经元CP染色与对照组相比有轻微但无统计学意义的增加。各神经退行性疾病组和对照组之间每视野CP染色神经元的数量没有差异。这些结果表明,AD脑中神经元CP含量有适度增加,本研究中其他神经退行性疾病的神经元CP有较小程度的升高。虽然CP在周围组织中既作为急性期蛋白又作为抗氧化剂发挥作用,但它在大脑中是否如此仍有待确定。