Prostaglandins, Leukotrienes and Essential Fatty Acids
Docosahexaenoic acid-induced changes in phospholipids in cortex of young and aged rats: A lipidomic analysis
Introduction
The ageing brain is characterised by neuronal deficits resulting in an impairment of cognitive function and memory decline. Changes in the neuronal cell membrane lipid composition, such as the age-related decline in the levels of polyunsaturated fatty acids (PUFA), can affect their biophysical properties, and influence the ability of membrane lipids to act as precursors of bioactive lipid mediators [1]. Dietary supplementation with fish oil, a rich source of n-3 PUFA, has been shown to improve the age-related decline in brain function [2], [3], [4], [5], [6] and the mechanism of this action is of interest.
Docosahexaenoic acid (DHA) (22:6n-3) is the predominant n-3 PUFA present in neural membranes. Its levels are determined during gestation and early postnatal life [7] and it is generally accepted that these levels are rigorously maintained in the adult essential-fatty acid sufficient animals. DHA modulates numerous cellular functions within the central nervous system including gene expression, cell signalling, neurotransmitter release and apoptosis [8], [9], [10], [11], [12]. The lack of easily available analytically pure single DHA preparations has resulted in most studies to rely on the use of fish oil as a source of n-3 PUFA for dietary supplementation. However, the presence of eicosapentaenoic acid (EPA) (20:5n-3) in these preparations can mask the effect of DHA, since those two biologically active n-3 PUFA are interconvertible. Consequently, the exact independent mechanism in which DHA exerts its beneficial function is yet to be fully elucidated.
The aim of the current study was to fingerprint the age-related changes in different lipid classes and monitor the remodelling of phospholipid species in the rat cortical tissue following supplementation with pure DHA, in an attempt to unravel aspects of its molecular mechanisms of action. We have used high-field 1H-NMR and electrospray ionisation/tandem mass spectrometry (ESI-MS/MS) to analyse complete lipid extracts. Here, we report modifications in the cortical lipids that can account for the observed beneficial activities of DHA.
Section snippets
Materials
l-α-Phosphatidylcholine, dipalmitoyl (PC), l-α-phosphatidylethanolamine, dipalmitoyl (PE), 1,2-diacyl-sn-glycero-3-phospho-d-myo-inositol (PI), l-α-phosphatidylserine, dipalmitoyl (PS), N-acyl-d-sphingosine-1-phosphocholine (SM), phosphate buffered saline tablets (PBS), butylated hydroxytoluene (BHT) and sodium sulphate were purchased from Sigma-Aldrich (Poole, Dorset, UK). HPLC-grade methanol and chloroform, ammonium hydroxide (10%) and absolute ethanol were purchased from Fischer Chemicals
1HNMR analysis of cortical tissue lipid extracts
Analysis of lipid extracts by high-field 1HNMR allowed the profiling of the major classes of lipids in the cortical tissue, the predominant PUFA (DHA and AA), and unsaturation index, a measure of total number of double bonds per fatty acid chain (Table 1). The observed age-related changes were reductions in the concentration of DHA, unsaturation index and total diacylglycerophospholipids, whilst the concentrations of sphingomyelin, sphingolipids and cholesterol were found to increase.
Discussion
Docosahexaenoic acid with its unique structure, physicochemical properties, and high prevalence in neuronal cell membrane, is an essential component for prenatal brain development and normal healthy function of the nervous system. Reductions in the neuronal content of DHA as observed in the ageing brain, have been correlated with cognitive decline and memory impairment [3], [5], [6]. We have previously shown [2] that a daily dose of 10 mg DHA attenuated the age-related impairment in long-term
Acknowledgements
The authors gratefully acknowledge the valuable advice of Dr. G. Koster and Dr. A.D. Postle (University of Southampton), and excellent technical support provided by A.R. Healey (Analytical Centre, University of Bradford).
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