Abstract:
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.
摘要:
与酒精有关的脑损伤的特征是认知缺陷和脑萎缩,前额叶皮层特别易感。人脑中的白质富含脂质,是慢性酒精滥用的主要损害目标;然而,关于这些脂质如何受到影响的信息很少。这里,我们使用非靶向脂质组学作为一种发现工具来描述前额叶的这些变化,中颞叶,以及患有酒精使用障碍和对照的人类受试者的视觉皮层。脂质组的显著变化,主要在前额叶和视觉皮层,并确定了每个大脑区域的白质和灰质之间的差异。这些影响包括磷脂和神经酰胺的广泛减少,减少多不饱和脂肪酸,减少了鞘二烯骨架,和胆固醇酯脂肪酸链的选择性减少。我们的发现表明,慢性酒精滥用会导致神经脂组的选择性变化,这可能反映了对大脑的直接影响和对肝脏的同时影响。