Brain Phospholipid Composition in Schizophrenia

描述(申请人提供)：对红细胞和血小板的研究表明，精神分裂症是由于大脑中磷脂(PL)代谢和成分的变化导致细胞膜异常引起的。基于细胞膜异常的精神分裂症假说可以潜在地解释一系列发现，并与多神经递质系统和神经发育异常相一致。体内31P核磁共振(31P核磁共振)对PL前体和降解产物的检测表明，精神分裂症患者的大脑PL代谢发生了变化。这些活体核磁共振研究的局限性是不能直接观察到PLs，因为它们是类固体的。为了让31P体内核磁共振结果有力地支持精神分裂症的膜假说，PL前体和降解产物的变化必须与大脑中PL组成的实际变化联系在一起。在我们实验室的31P体外核磁共振初步研究中，与对照组相比，死后精神分裂症脑(额叶皮质)提取物中的磷脂酰肌醇、带有一条饱和和一条不饱和侧链的磷脂酰胆碱升高，以及总磷脂酰胆碱含量有增加的趋势。这些结果支持了精神分裂症患者大脑中存在PL异常的观点。假设精神分裂症患者的额叶和颞叶皮质(但不包括枕叶皮质)的PL成分与对照组不同。还假设，在体内31P核磁共振检测到PL前体和/或降解产物的变化的情况下，PL组成的变化也在发生。用31P体外核磁共振技术测定了同一个体(20例精神分裂症患者、20例对照组和10例精神病对照组)左侧额叶、颞叶和枕叶的PL组成(有机溶剂提取物和胆盐增溶作用)以及PL前体和降解产物(高氯酸提取物)。这项研究将阐明以前关于外周组织和活体的PL研究有时相互矛盾的结果。它还可能为精神分裂症的膜假说的几个方面提供支持和澄清。

DESCRIPTION (provided by applicant): Studies of erythrocytes and platelets have suggested that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) metabolism and composition in the brain. A hypothesis of schizophrenia based on cell membrane abnormalities can potentially explain a range of findings, and is consistent with abnormalities in multiple neurotransmitter systems and neurodevelopment. Examination of PL precursors and degradation products by in vivo 31P nuclear magnetic resonance (NMR) suggests alterations in brain PL metabolism in schizophrenia. A limitation of these in vivo NMR studies is that PLs are not observed directly because they are solid-like. For the 31 P in vivo NMR results to support strongly the membrane hypothesis of schizophrenia, changes in PL precursors and degradation products must be linked with actual changes in PL composition in the brain. In preliminary studies in our lab using 31P in vitro NMR, elevated phosphatidylinositol, elevated phosphatidylcholine with one saturated and one unsaturated side chain, and a trend toward increased total PLs, were found in extracts of postmortem schizophrenic brain (frontal cortex) relative to control. These results support the notion that PL abnormalities occur in the brain in schizophrenia. It is hypothesized that the PL compositions in frontal and temporal cortices (but not occipital cortex), regions implicated in schizophrenia, are different in schizophrenics than in controls. It is also hypothesized that, in the cases where in vivo 31 P NMR detects changes in PL precursors and/or degradation products, changes in PL composition are also occurring. It is proposed to measure both the PL composition (organic solvent extract and bile-salt solubilization) and PL precursors and degradation products (perchloric acid extract) in left frontal, temporal and occipital cortices of the same individuals (20 schizophrenics, 20 controls, and 10 psychiatric controls) using 31 P in vitro NMR. This study will shed light on the sometimes conflicting results of previous PL studies both on peripheral tissue and in vivo. It will also potentially provide support and clarification for several aspects of the membrane hypothesis of schizophrenia.