Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, 4710-057, Portugal.
ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, 4710-057, Portugal.
Transl Psychiatry. 2019 Apr 26;9(1):144. doi: 10.1038/s41398-019-0478-6.
Lipids are major constituents of the brain largely implicated in physiological and pathological processes. The hippocampus is a complex brain structure involved in learning, memory and emotional responses, and its functioning is also affected in various disorders. Despite conserved intrinsic circuitry, behavioral and anatomical studies suggest the existence of a structural and functional gradient along the hippocampal longitudinal axis. Here, we used an unbiased mass spectrometry approach to characterize the lipid composition of distinct hippocampal subregions. In addition, we evaluated the susceptibility of each area to lipid modulation by corticosterone (CORT), an important mediator of the effects of stress. We confirmed a great similarity between hippocampal subregions relatively to other brain areas. Moreover, we observed a continuous molecular gradient along the longitudinal axis of the hippocampus, with the dorsal and ventral extremities differing significantly from each other, particularly in the relative abundance of sphingolipids and phospholipids. Also, whereas chronic CORT exposure led to remodeling of triacylglycerol and phosphatidylinositol species in both hippocampal poles, our study suggests that the ventral hippocampus is more sensitive to CORT-induced changes, with regional modulation of ceramide, dihydrosphingomyelin and phosphatidic acid. Thus, our results confirm a multipartite molecular view of dorsal-ventral hippocampal axis and emphasize lipid metabolites as candidate effectors of glucocorticoid signaling, mediating regional susceptibility to neurological disorders associated with stress.
脂质是大脑的主要成分，在生理和病理过程中起着重要作用。海马体是一个复杂的脑结构，参与学习、记忆和情绪反应，其功能也受到各种疾病的影响。尽管存在保守的内在电路，但行为和解剖学研究表明，海马体的纵向轴上存在结构和功能的梯度。在这里，我们使用一种无偏的质谱方法来描述不同海马亚区的脂质组成。此外，我们评估了每个区域对皮质酮（CORT）的脂质调节的敏感性，CORT 是应激影响的重要介质。我们证实了海马亚区与其他脑区之间存在很大的相似性。此外，我们观察到沿着海马体的纵向轴存在连续的分子梯度，背侧和腹侧末端彼此显著不同，特别是鞘脂和磷脂的相对丰度。而且，虽然慢性 CORT 暴露导致两个海马极中的三酰甘油和磷脂种类的重塑，但我们的研究表明，腹侧海马体对 CORT 诱导的变化更为敏感，神经酰胺、二氢神经鞘氨醇和磷脂酸的区域性调节。因此，我们的结果证实了背-腹海马体轴的多部分分子观点，并强调脂质代谢物作为糖皮质激素信号传导的候选效应物，介导与应激相关的神经障碍的区域易感性。
