Minghui Li1, Yan Gao1, Dandan Wang1, Xiaowen Hu1, Jie Jiang1, Ying Qing1, Xuhan Yang1, Gaoping Cui1, Pengkun Wang1, Juan Zhang1, Liya Sun1,2, Chunling Wan1,3. 1. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. 2. Shanghai Mental Health Center, Editorial Office, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. 3. Shanghai Mental Health Center, Shanghai Key Laboratory of Psychiatry Disorders, Shanghai Jiao Tong University, Shanghai, China.
Abstract
BACKGROUND AND HYPOTHESIS: Multiple lines of clinical, biochemical, and genetic evidence suggest that disturbances of membrane lipids and their metabolism are probably involved in the etiology of schizophrenia (SCZ). Lipids in the membrane are essential to neural development and brain function, however, their role in SCZ remains largely unexplored. STUDY DESIGN: Here we investigated the lipidome of the erythrocyte membrane of 80 patients with SCZ and 40 healthy controls using ultra-performance liquid chromatography-mass spectrometry. Based on the membrane lipids profiling, we explored the potential mechanism of membrane phospholipids metabolism. STUDY RESULTS: By comparing 812 quantified lipids, we found that in SCZ, membrane phosphatidylcholines and phosphatidylethanolamines, especially the plasmalogen, were significantly decreased. In addition, the total polyunsaturated fatty acids (PUFAs) in the membrane of SCZ were significantly reduced, resulting in a decrease in membrane fluidity. The accumulation of membrane oxidized lipids and the level of peripheral lipid peroxides increased, suggesting an elevated level of oxidative stress in SCZ. Further study of membrane-phospholipid-remodeling genes showed that activation of PLA2s and LPCATs expression in patients, supporting the imbalance of unsaturated and saturated fatty acyl remodeling in phospholipids of SCZ patients. CONCLUSIONS: Our results suggest that the mechanism of impaired membrane lipid homeostasis is related to the activated phospholipid remodeling caused by excessive oxidative stress in SCZ. Disordered membrane lipids found in this study may reflect the membrane dysfunction in the central nervous system and impact neurotransmitter transmission in patients with SCZ, providing new evidence for the membrane lipids hypothesis of SCZ.
BACKGROUND AND HYPOTHESIS: Multiple lines of clinical, biochemical, and genetic evidence suggest that disturbances of membrane lipids and their metabolism are probably involved in the etiology of schizophrenia (SCZ). Lipids in the membrane are essential to neural development and brain function, however, their role in SCZ remains largely unexplored. STUDY DESIGN: Here we investigated the lipidome of the erythrocyte membrane of 80 patients with SCZ and 40 healthy controls using ultra-performance liquid chromatography-mass spectrometry. Based on the membrane lipids profiling, we explored the potential mechanism of membrane phospholipids metabolism. STUDY RESULTS: By comparing 812 quantified lipids, we found that in SCZ, membrane phosphatidylcholines and phosphatidylethanolamines, especially the plasmalogen, were significantly decreased. In addition, the total polyunsaturated fatty acids (PUFAs) in the membrane of SCZ were significantly reduced, resulting in a decrease in membrane fluidity. The accumulation of membrane oxidized lipids and the level of peripheral lipid peroxides increased, suggesting an elevated level of oxidative stress in SCZ. Further study of membrane-phospholipid-remodeling genes showed that activation of PLA2s and LPCATs expression in patients, supporting the imbalance of unsaturated and saturated fatty acyl remodeling in phospholipids of SCZ patients. CONCLUSIONS: Our results suggest that the mechanism of impaired membrane lipid homeostasis is related to the activated phospholipid remodeling caused by excessive oxidative stress in SCZ. Disordered membrane lipids found in this study may reflect the membrane dysfunction in the central nervous system and impact neurotransmitter transmission in patients with SCZ, providing new evidence for the membrane lipids hypothesis of SCZ.
Authors: Andrea Schmitt; Katrin Wilczek; Kaj Blennow; Athanasios Maras; Alexander Jatzko; Georg Petroianu; Dieter F Braus; Wagner F Gattaz Journal: Biol Psychiatry Date: 2004-07-01 Impact factor: 13.382
Authors: C Tessier; K Sweers; A Frajerman; H Bergaoui; F Ferreri; C Delva; N Lapidus; A Lamaziere; J P Roiser; M De Hert; P Nuss Journal: Transl Psychiatry Date: 2016-10-04 Impact factor: 6.222