Abstract
Lipids play a major role for several brain functions, including cognition and memory. There is a series of work on individual lipids showing involvement in memory mechanisms, a concise lipidome was not reported so far. Moreover, there is no evidence for age-related memory decline and there is only work on brain of young vs. aging animals. Aging animals, however, are not a homogeneous group with respect to memory impairments, thus animals with impaired and unimpaired memory can be discriminated. Following recent studies of hippocampal lipid profiles and hypothalamus controlled hormone profiles, the aim of this study was to compare hypothalamic, lipidomic changes in male Sprague-Dawley rats between young (YM), old impaired (OMI) and old unimpaired (OMU) males. Grouping criterions for aged rats were evaluated by testing them in a spatial memory task, the hole-board. YMs were also tested. Subsequently brains were removed, dissected and hypothalami were kept at −80°C until sample preparation and analysis on liquid chromatography / mass spectrometry (LC-MS). Significant differences in the amounts of a series of lipids from several classes could be detected between young and aged and between OMI and OMU. A large number of lipids were increased in OMI and a smaller number in OMU as compared to young rats. Differences of lipid ratios (log2 of ratio) between OMI and OMU consisted of glycerophosphocholines (aPC 36:2 and 36:3; PC 34:0, 36:1, 36:3 and 40:2); Glycerophosphoethanolamines (aPE 34:2, 38:5 and 40:5; LPE 18:1, 20:1, 20:4, 22:4 and 22:6; PE36:1 and 38:4); glycerophosphoserines (PS 36:1, 40:4, and 40:6); triacylglycerol TG 52:4; ceramide Cer 17:2 and sphingomyelin SM 20:0. Thus, hypothalamic lipid profiles across different lipid classes discriminate aged male animals into OMU and OMI. The underlying mechanisms may be related to different functional networks of lipids in memory mechanisms and differences in metabolic processes. The study underlines the importance of lipidomics in the pathophysiology of age-related cognitive decline. The necessity of evaluating the cognitive status of aged subjects by behavioral tests results in more specific detection of critical lipids in memory decline, on which now can be focused in subsequent memory studies in animals and humans.
Highlights
Lipids play a pivotal role in the regulation of brain functions (Piomelli et al, 2007; Chan et al, 2012)
In previous studies we focused on differences in hippocampal lipid profiles in good and bad learners (Malikovicet al., 2019a) as well as steroid and thyroid hormone levels between young male rats, comparable in terms of spatial memory performance to OMU and OMI male rats selected from a large cohort by a spatial memory paradigm, the hole-board (Malikovicet al., 2019b)
We found differences in the hypothalamic lipid contents especially when YM and OMI male rats were compared, whereas the number of lipids that differed between YM and OMU
Summary
Lipids play a pivotal role in the regulation of brain functions (Piomelli et al, 2007; Chan et al, 2012). A most useful review article (Morley and Banks, 2010) is reporting the role of lipids in cognition, stating that cholesterol, omega-3-fatty acids and triglycerides have been postulated to modulate cognition in humans, both, in health and disease. In this critical review it is made clear that results from experimental treatments with lipids are not unequivocal, it is concluded that obesity as well as lipid loads by nutrition are linked to cognitive decline. Lipid consumption modulate blood pressure and cardiovascular – as well as cerebrovascular – function thereby contributing to cognitive performance (De Wilde et al, 2003). The work is focusing on individual lipids the introduction and development of mass spectrometric techniques with the aim to generate brain lipidomes has allowed deeper insight into lipid composition and mechanisms in several species and a series of brain subregions and subareas (Köfeler et al, 2010; Oliveira et al, 2016; Smidak et al, 2017b; Lerner et al, 2019; Malikovicet al., 2019b)
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