Faculty of Medicine and Health, School of Medical Sciences and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
Centenery Institute, The University of Sydney, Sydney, New South Wales, Australia.
J Neurochem. 2022 Jan;160(2):271-282. doi: 10.1111/jnc.15530. Epub 2021 Nov 11.
Alcohol-related brain injury is characterized by cognitive deficits and brain atrophy with the prefrontal cortex particularly susceptible. White matter in the human brain is lipid rich and a major target of damage from chronic alcohol abuse; yet, there is sparse information on how these lipids are affected. Here, we used untargeted lipidomics as a discovery tool to describe these changes in the prefrontal, middle temporal, and visual cortices of human subjects with alcohol use disorder and controls. Significant changes to the lipidome, predominantly in the prefrontal and visual cortices, and differences between the white and grey matter of each brain region were identified. These effects include broad decreases to phospholipids and ceramide, decreased polyunsaturated fatty acids, decreased sphingadiene backbones, and selective decreases in cholesteryl ester fatty acid chains. Our findings show that chronic alcohol abuse results in selective changes to the neurolipidome, which likely reflects both the directs effects on the brain and concurrent effects on the liver.
酒精相关的脑损伤的特征是认知缺陷和脑萎缩，其中前额叶皮层特别容易受到影响。人类大脑的白质富含脂质，是慢性酒精滥用损害的主要靶点；然而，关于这些脂质如何受到影响的信息却很少。在这里，我们使用非靶向脂质组学作为一种发现工具，来描述酒精使用障碍患者和对照组的前额叶、中颞叶和视觉皮层中的这些变化。确定了脂质组的显著变化，主要在前额叶和视觉皮层中，以及每个脑区的白质和灰质之间的差异。这些影响包括磷脂和神经酰胺广泛减少，多不饱和脂肪酸减少，鞘氨醇骨架减少，以及胆固醇酯脂肪酸链的选择性减少。我们的研究结果表明，慢性酒精滥用会导致神经脂质组的选择性变化，这可能既反映了对大脑的直接影响，也反映了对肝脏的并发影响。
