Nitsch R M, Blusztajn J K, Doyle F M, Robitaille Y, Wurtman R J, Growdon J H, Kish S J
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Neurosci Lett. 1993 Oct 29;161(2):191-4. doi: 10.1016/0304-3940(93)90291-r.
We measured metabolic precursors and breakdown products of phosphatidylcholine (choline, glycerophosphocholine (GPC) and phosphatidylethanolamine (ethanolamine, glycerophosphoethanolamine (GPE)) as well as the amino acid serine, a precursor of phosphatidylserine, in four morphologically unaffected cerebral cortical areas obtained at autopsy from 14 patients with dominantly inherited olivopontocerebellar atrophy (OPCA) and 13 controls matched for age and postmortem interval. As compared with the controls, mean GPE levels were elevated by 49-57% in frontal and parietal cortices of OPCA brains whereas concentrations of ethanolamine were significantly reduced in temporal, occipital and parietal cortex (-40 to -54%). This resulted in increased GPE/ethanolamine ratios (+80 to +146%). GPC levels were significantly increased (by 53%) in the frontal cortex of OPCA patients relative to controls. Free serine levels were reduced by 20 to 28% in frontal, parietal, temporal, and occipital cortices. These abnormalities in phospholipid metabolite levels in OPCA resemble those seen in Alzheimer's disease, although the changes in GPC are less pronounced. These changes in phospholipid metabolism in OPCA cerebral cortex, a brain area spared from neurodegenerative changes, points to generalized disturbances in cellular membrane function in this disease.
我们在14例常染色体显性遗传性橄榄体脑桥小脑萎缩（OPCA）患者尸检时获取的4个形态学未受影响的大脑皮质区域中，测量了磷脂酰胆碱的代谢前体和分解产物（胆碱、甘油磷酸胆碱（GPC）和磷脂酰乙醇胺（乙醇胺、甘油磷酸乙醇胺（GPE）））以及磷脂酰丝氨酸的前体氨基酸丝氨酸，并与13例年龄和死后间隔相匹配的对照者进行了比较。与对照组相比，OPCA患者大脑额叶和顶叶皮质中的平均GPE水平升高了49% - 57%，而颞叶、枕叶和顶叶皮质中的乙醇胺浓度显著降低（-40%至-54%）。这导致GPE/乙醇胺比值升高（+80%至+146%）。相对于对照组，OPCA患者额叶皮质中的GPC水平显著升高（53%）。额叶、顶叶、颞叶和枕叶皮质中的游离丝氨酸水平降低了20%至28%。OPCA患者磷脂代谢产物水平的这些异常类似于阿尔茨海默病中的情况，尽管GPC的变化不太明显。OPCA大脑皮质是一个未发生神经退行性改变的脑区，其磷脂代谢的这些变化表明该疾病存在细胞膜功能的普遍紊乱。
