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.
Highlights
Brain lipids are attracting focused attention in neurochemistry as information carrying molecules that affect the biological processes by both, modifying membrane structures and direct interaction with other signaling molecules [1,2]
Changed lipid species were identified by accurate (+/- 5 ppm) precursor mass matching with an internal lipid database which covers more than 20,000 molecular lipid species originating from 58 individual lipidclasses
Based on the Lipid MAPS classification system the identified lipid molecules have been assigned to four main lipid classes: glycerolipids, glycerophospholipids, sphingolipids and sterol lipids spanning ten distinct lipid subclasses: di- and triacylglycerols, glycerophosphates, glycerophospho- / -cholines / -ethanolamines / -serines, glycerophosphoglycerophosphoglycerols, ceramides, sphingomyelins and sterols
Summary
Brain lipids are attracting focused attention in neurochemistry as information carrying molecules that affect the biological processes by both, modifying membrane structures and direct interaction with other signaling molecules [1,2]. The numerous functions of lipids reflect their high structural and combinatorial diversity that makes lipidomic analyses experimentally challenging [3]. These analyses have been frequently hampered by sampling problem, extraction procedures as well as instability in postmortem tissues [4]. Bozek et al [6] recently used an MS-based non-targeted approach to comprehensively characterize the tissue-specific lipid composition in different mammalian models. Based on analysis of over 5,000 hydrophobic compounds the authors showed that the brain was significantly different as compared to other non-neural tissues and highlighted the specific role of neural lipids. A series of other studies revealed brain lipid changes in association with Alzheimer’s disease (AD) [7,8], Parkinson’s disease [9,10] or schizophrenia [11,12] and supported the relevance of lipidomic analyses of model organisms for studying neurological disorders [13,14]
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