Differential lipid composition and regulation along the hippocampal longitudinal axis

Abstract

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.