Comprehensive identification of age-related lipidome changes in rat amygdala during normal aging

Abstract

Brain lipids are integral components of brain structure and function. However, only recent advancements of chromatographic techniques together with mass spectrometry allow comprehensive identification of lipid species in complex brain tissue. Lipid composition varies between the individual areas and the majority of previous reports was focusing on individual lipids rather than a lipidome. Herein, a mass spectrometry-based approach was used to evaluate age-related changes in the lipidome of the rat amygdala obtained from young (3 months) and old (20 months) males of the Sprague-Dawley rat strain. A total number of 70 lipid species with significantly changed levels between the two animal groups were identified spanning four main lipid classes, i.e. glycerolipids, glycerophospholipids, sphingolipids and sterol lipids. These included phospholipids with pleiotropic brain function, such as derivatives of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine. The analysis also revealed significant level changes of phosphatidic acid, diacylglycerol, sphingomyelin and ceramide that directly represent lipid signaling and affect amygdala neuronal activity. The amygdala is a crucial brain region for cognitive functions and former studies on rats and humans showed that this region changes its activity during normal aging. As the information on amygdala lipidome is very limited the results obtained in the present study represent a significant novelty and may contribute to further studies on the role of lipid molecules in age-associated changes of amygdala function.

Fig 1. Level changes of the molecular species of hexosylceramides (HexCer) and alkyl-/acylglycerophospholipids (aPC) significantly dysregulated in the amygdalae of aged vs. young rats.

Individual lipid molecules were differentially regulated based on length and saturation of fatty acyl chains. Lipid species are denoted as AA X:Y based on the abbreviation of lipid molecule (AA), the total number of carbons (X) and the total number of double bonds (Y) in their acyl side chains. The values are represented as base 2 logarithm of the aged vs. young ratio of averaged peak areas ± SEM.

Fig 2. Level changes of important signaling lipids dysregulated in the amygdalae of aged vs. young rats.

Several molecules of glycerophospholipids (first graph): phosphatidic acid (PA), diacylglycerols (DG) and glycerophosphocholines (PC), and members of sphingolipids (second graph): sphingomyelins (SM), ceramides (Cer) and its derivatives hexosylceramides, hexosyldihydroceramides (HexDHCer) and dihydroceramides (DHCer) have shown significantly different levels in the amygdalae of aged as compared to young rats. Lipid species are denoted as AA X:Y based on the abbreviation of lipid molecule (AA), the total number of carbons (X) and the total number of double bonds (Y) in their acyl side chains. The values are represented as base 2 logarithm of the old/young ratio of averaged peak areas ± SEM.