Department of Psychiatry, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
Department of Pharmacology, 2176 Health Sciences Mall, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
Schizophr Res. 2020 Jan;215:493-498. doi: 10.1016/j.schres.2017.05.033. Epub 2017 Jun 3.
The extracellular matrix protein reelin regulates early brain development and synaptic plasticity in adulthood. Reelin is decreased in the postmortem brain in schizophrenia patients. Reelin's two receptors, ApoER2 and VLDLR, are also substrates for ApoE - a key lipoprotein that regulates phospholipid homeostasis in the brain. The goal of the present study was therefore to examine phospholipids and their constituent fatty acids, and determine whether there is an association between reelin, its receptors and phospholipids in the brain.
Dorsolateral prefrontal cortex (BA9) grey matter was obtained from the Stanley Foundation Neuropathology Consortium. Samples included tissue from 35 controls, 35 schizophrenia and 34 bipolar disorder patients. Phospholipids were measured using gas liquid chromatography.
We quantified 15 individual fatty acid or plasmalogen species for phosphatidylethanolamine and phosphatidylcholine fractions, each comprising >0.5% of the total fatty acid pool. There were no group differences in phospholipids or individual fatty acid species after correcting for multiple comparisons. However, for the entire cohort, both the polyunsaturated subclass of fatty acids, and ApoE, correlated significantly with reelin expression, with a number of individual ω-6 fatty acid species also demonstrating a significant positive correlation. There was a non-significant trend for similar effects with VLDLR expression as for reelin.
Phospholipids and fatty acids in the dorsolateral cortex do not differ in patients with schizophrenia, bipolar disorder and controls. Reelin expression in this brain region is associated with polyunsaturated fatty acids and ApoE, suggesting further study of potential physiological interactions between these substrates is warranted.
细胞外基质蛋白 reelin 调节大脑早期发育和成年期的突触可塑性。精神分裂症患者死后大脑中的 reelin 减少。reelin 的两个受体，ApoER2 和 VLDLR，也是 ApoE 的底物 - ApoE 是一种关键的脂蛋白，调节大脑中的磷脂稳态。因此，本研究的目的是检查磷脂及其组成脂肪酸，以及确定 reelin、其受体和大脑中的磷脂之间是否存在关联。
从斯坦利基金会神经病理学联合会获得背外侧前额叶皮质（BA9）灰质。样本包括 35 名对照、35 名精神分裂症和 34 名双相情感障碍患者的组织。使用气相色谱法测量磷脂。
我们定量了磷脂酰乙醇胺和磷脂酰胆碱部分的 15 种个体脂肪酸或溶血磷脂种类，每种占总脂肪酸池的>0.5%。在进行多次比较校正后，磷脂或个体脂肪酸种类在各组之间没有差异。然而，对于整个队列，多不饱和脂肪酸亚类和 ApoE 与 reelin 表达显著相关，许多个体 ω-6 脂肪酸种类也表现出显著的正相关。VLDLR 表达与 reelin 相似，存在非显著的趋势。
精神分裂症、双相情感障碍和对照组患者背外侧皮质的磷脂和脂肪酸没有差异。该脑区的 reelin 表达与多不饱和脂肪酸和 ApoE 相关，表明需要进一步研究这些底物之间潜在的生理相互作用。
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