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The Journal of Neuroscience : the... Sep 2019Epidemiological studies suggest that poor nutrition during pregnancy influences offspring predisposition to experience developmental and psychiatric disorders. Animal...
Epidemiological studies suggest that poor nutrition during pregnancy influences offspring predisposition to experience developmental and psychiatric disorders. Animal studies have shown that maternal undernutrition leads to behavioral impairment, which is linked to alterations in monoaminergic systems and inflammation in the brain. In this study, we focused on the ethanolamine plasmalogen of the brain as a possible contributor to behavioral disturbances observed in offspring exposed to maternal undernutrition. Maternal food or protein restriction between gestational day (GD) 5.5 and GD 10.5 resulted in hyperactivity of rat male adult offspring. Genes related to the phospholipid biosynthesis were found to be activated in the PFC, but not in the NAcc or striatum, in the offspring exposed to prenatal undernutrition. Corresponding to these gene activations, increased ethanolamine plasmalogen (18:0p-22:6) was observed in the PFC using mass spectrometry imaging. A high number of crossings and the long time spent in the center area were observed in the offspring exposed to prenatal undernutrition and were mimicked in adult rats via the intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome. Additionally, plasmalogen (18:0p-22:6) increased only in the PFC, and not in the NAcc or striatum. These results suggest that brain plasmalogen is one of the key molecules to control behavior, and its injection using liposome is a potential therapeutic approach for cognitive impairment. Maternal undernutrition correlates to developmental and psychiatric disorders. Here, we found that maternal undernutrition in early pregnancy led to hyperactivity in rat male offspring and induced gene activation of phospholipid-synthesizing enzyme and elevation of ethanolamine plasmalogen (18:0p-22:6) level in the PFC. Intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome maintained crossing activity and the activity was circumscribed to the center area for a long time period, as in prenatally undernourished offspring with aberrant behavior. Furthermore, the amount of ethanolamine plasmalogen (18:0p-22:6) increased in the PFC of the rat after injection. Our result suggests that brain plasmalogen is one of the key molecules to control behavior and that its injection using liposome is a potential therapeutic approach for cognitive impairment.
Topics: Animals; Behavior, Animal; Female; Male; Malnutrition; Plasmalogens; Prefrontal Cortex; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar
PubMed: 31391260
DOI: 10.1523/JNEUROSCI.2721-18.2019 -
The Journal of Biological Chemistry Mar 2020An early exposure to lipid biochemistry in the laboratory of Konrad Bloch resulted in a fascination with the biosynthesis, structures, and functions of bacterial lipids....
An early exposure to lipid biochemistry in the laboratory of Konrad Bloch resulted in a fascination with the biosynthesis, structures, and functions of bacterial lipids. The discovery of plasmalogens (1-alk-1'-enyl, 2-acyl phospholipids) in anaerobic Gram-positive bacteria led to studies on the physical chemistry of these lipids and the cellular regulation of membrane lipid polymorphism in bacteria. Later studies in several laboratories showed that the formation of the alk-1-enyl ether bond involves an aerobic process in animal cells and thus is fundamentally different from that in anaerobic organisms. Our work provides evidence for an anaerobic process in which plasmalogens are formed from their corresponding diacyl lipids. Studies on the roles of phospholipases in revealed distinctions between its phospholipases and those previously discovered in other bacteria and showed how the enzymes are uniquely fitted to the intracellular lifestyle of this significant human pathogen.
Topics: Anaerobiosis; Bacteria, Anaerobic; Fatty Acids; Gram-Positive Bacteria; Lipids; Phosphatidylethanolamines; Plasmalogens
PubMed: 32221031
DOI: 10.1074/jbc.X120.013022 -
Journal of Neurochemistry May 2001To explore the hypothesis that alterations in ethanolamine plasmalogen may be directly related to the severity of dementia in Alzheimer's disease (AD), we performed a...
To explore the hypothesis that alterations in ethanolamine plasmalogen may be directly related to the severity of dementia in Alzheimer's disease (AD), we performed a systematic examination of plasmalogen content in cellular membranes of gray and white matter from different regions of human subjects with a spectrum of AD clinical dementia ratings (CDR) using electrospray ionization mass spectrometry (ESI/MS). The results demonstrate: (1) a dramatic decrease in plasmalogen content (up to 40 mol% of total plasmalogen) in white matter at a very early stage of AD (i.e. CDR 0.5); (2) a correlation of the deficiency in gray matter plasmalogen content with the AD CDR (i.e. approximately 10 mol% of deficiency at CDR 0.5 (very mild dementia) to approximately 30 mol% of deficiency at CDR 3 (severe dementia); (3) an absence of alterations of plasmalogen content and molecular species in cerebellar gray matter at any CDR despite dramatic alterations of plasmalogen content in cerebellar white matter. Alterations of ethanolamine plasmalogen content in two mouse models of AD, APP(V717F) and APPsw, were also examined by ESI/MS. A plasmalogen deficiency was present (up to 10 mol% of total plasmalogen at the age of 18 months) in cerebral cortices, but was absent in cerebella from both animal models. These results suggest plasmalogen deficiency may play an important role in the AD pathogenesis, particularly in the white matter, and suggest that altered plasmalogen content may contribute to neurodegeneration, synapse loss and synaptic dysfunction in AD.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Animals; Apolipoproteins E; Autopsy; Brain; Brain Chemistry; Disease Models, Animal; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; Mice, Transgenic; Phospholipids; Plasmalogens; Spectrometry, Mass, Electrospray Ionization
PubMed: 11359882
DOI: 10.1046/j.1471-4159.2001.00332.x -
Chemistry and Physics of Lipids Jul 2011The naturally occurring 1-O-alkyl-sn-glycerols and their methoxylated congeners, 1-O-(2'-methoxyalkyl)-sn-glycerols, are biologically active compounds, ubiquitously...
The naturally occurring 1-O-alkyl-sn-glycerols and their methoxylated congeners, 1-O-(2'-methoxyalkyl)-sn-glycerols, are biologically active compounds, ubiquitously found in nature as diacyl glyceryl ether lipids and phosphoether lipids. The chief objective of this article is to provide a comprehensive and up to date review on such ether lipids. The occurrence and distribution of these compounds in nature are extensively reviewed, their chemical structure and molecular variety, their biosynthesis and chemical synthesis and, finally, their various biological effects are described and discussed. An unprecedented biosynthesis of the 2'-methoxylated alkylglycerols is proposed. The first synthesis of enantiopure (Z)-(2'R)-1-O-(2'-methoxyhexadec-4'-enyl)-sn-glycerol, the most prevalent 2'-methoxylated type alkylglycerol present in cartilaginous fish, is described. It was accomplished by a highly convergent five step process.
Topics: Glycerol; Glyceryl Ethers; Lipids; Plasmalogens; Protein Kinase C; Stereoisomerism
PubMed: 21635876
DOI: 10.1016/j.chemphyslip.2011.04.010 -
Advances in Experimental Medicine and... 2020Plasmalogens (Pls) are one kind of phospholipids enriched in the brain and other organs. These lipids were thought to be involved in the membrane bilayer formation and... (Review)
Review
Plasmalogens (Pls) are one kind of phospholipids enriched in the brain and other organs. These lipids were thought to be involved in the membrane bilayer formation and anti-oxidant function. However, extensive studies revealed that Pls exhibit various beneficial biological activities including prevention of neuroinflammation, improvement of cognitive function, and inhibition of neuronal cell death. The biological activities of Pls were associated with the changes in cellular signaling and gene expression. Membrane-bound GPCRs were identified as possible receptors of Pls, suggesting that Pls might function as ligands or hormones. Aging, stress, and inflammatory stimuli reduced the Pls contents in cells, and addition of Pls inhibited inflammatory processes, which could suggest that reduction of Pls might be one of the risk factors for the diseases associated with inflammation. Oral ingestion of Pls showed promising health benefits among Alzheimer's disease (AD) patients, suggesting that Pls might have therapeutic potential in other neurodegenerative diseases.
Topics: Alzheimer Disease; Brain; Cell Death; Humans; Inflammation; Plasmalogens
PubMed: 33417215
DOI: 10.1007/978-3-030-60204-8_13 -
Journal of Biochemistry May 2015Plasmalogens (Pls) are widely distributed in the biological membrane of animals and certain anaerobic bacteria, but their functions in the cell membrane are still poorly...
Plasmalogens (Pls) are widely distributed in the biological membrane of animals and certain anaerobic bacteria, but their functions in the cell membrane are still poorly understood. Decrease of phosphatidylethanolamine plasmalogen (PEPls) in the brain tissue of patients with Alzheimer's disease prompted us to investigate the effect of the membrane phosphorus lipid composition on the activity of γ-secretase that produces amyloid-beta protein (Aβ). To clarify the effect of phospholipids, including PEPls, on Aβ production, γ-secretase activity was measured in an in vitro assay using yeast microsomes and reconstituted liposomes. The presence of ethanolamine phospholipids in the proteoliposome weakened γ-secretase activity. In addition, increased PEPls content in total ethanolamine phospholipids further decreased the enzyme activity, indicating that γ-secretase activity is affected by the membrane phospholipid PEPls/PE ratio. Furthermore, PEPls from anaerobic bacterial cell membrane induced the same effect on γ-secretase activity.
Topics: Amyloid Precursor Protein Secretases; Animals; Humans; Phosphatidylethanolamines; Plasmalogens; Proteolipids
PubMed: 25409699
DOI: 10.1093/jb/mvu074 -
Lipids in Health and Disease Jun 2011Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane...
BACKGROUND
Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease.
RESULTS
In a human and great ape cohort, we measured the red blood cell (RBC) levels of the most abundant types of plasmalogens. Total RBC plasmalogen levels were lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. There were especially pronounced cross-species differences in the levels of plasmalogens with a C16:0 moiety at the sn-1 position. Humans on Western or vegan diets had comparable total RBC plasmalogen levels, but the latter group showed moderately higher levels of plasmalogens with a C18:1 moiety at the sn-1 position. We did not find robust sex-specific differences in human or chimpanzee RBC plasmalogen levels or composition. Furthermore, human and great ape skin fibroblasts showed only modest differences in peroxisomal plasmalogen biosynthetic activity. Human and chimpanzee microarray data indicated that genes involved in plasmalogen biosynthesis show cross-species differential expression in multiple tissues.
CONCLUSION
We propose that the observed differences in human and great ape RBC plasmalogens are primarily caused by their rates of biosynthesis and/or turnover. Gene expression data raise the possibility that other human and great ape cells and tissues differ in plasmalogen levels. Based on the phenotypes of humans and rodents with plasmalogen disorders, we propose that cross-species differences in tissue plasmalogen levels could influence organ functions and processes ranging from cognition to reproduction to aging.
Topics: Animals; Biosynthetic Pathways; Cells, Cultured; Diet, Vegetarian; Erythrocytes; Female; Fibroblasts; Gene Expression Profiling; Gene Expression Regulation; Gorilla gorilla; Humans; Male; Pan paniscus; Pan troglodytes; Peroxisomes; Phospholipids; Phylogeny; Plasmalogens; Pongo pygmaeus
PubMed: 21679470
DOI: 10.1186/1476-511X-10-101 -
Trends in Endocrinology and Metabolism:... Oct 2019The global prevalence of obesity continues to increase, suggesting a need for alternative treatment approaches. Targeting brown fat function to promote energy... (Review)
Review
The global prevalence of obesity continues to increase, suggesting a need for alternative treatment approaches. Targeting brown fat function to promote energy expenditure represents one such approach. Brown adipocytes and the related beige adipocytes oxidize fatty acids and glucose to generate heat and are activated by cold exposure or consumption of high-calorie diets. Alternative, more practical means to activate thermogenic fat are needed. Here, we review emerging data suggesting new roles for lipids in activating thermogenesis that extend beyond their serving as a fuel source for heat generation. Lipids have also been implicated in mediating interorgan communication, crosstalk between organelles, and cellular signaling regulating thermogenesis. Understanding how lipids regulate thermogenesis could identify innovative therapeutic interventions for obesity.
Topics: Adipose Tissue, Beige; Animals; Humans; Mitochondria; Obesity; Plasmalogens; Thermogenesis
PubMed: 31422871
DOI: 10.1016/j.tem.2019.07.020 -
FEBS Letters Sep 2017The biosynthesis of plasmalogens in anaerobic bacteria differs fundamentally from that in animal cells. Firstly, the formation of the alk-1'-enyl ether bond in animal... (Review)
Review
The biosynthesis of plasmalogens in anaerobic bacteria differs fundamentally from that in animal cells. Firstly, the formation of the alk-1'-enyl ether bond in animal cells is oxygen dependent. Secondly, the first step in plasmalogen formation in animal cells is an acylation of dihydroxyacetone phosphate, which has been ruled out as a precursor in anaerobes. In bacteria the alk-1'-enyl ether bond is formed after the fully formed acyl glycerolipids are synthesized. Evidence will be presented for the conversion of the sn-1 acyl-linked chain to an O-alk-1'-enyl ether by an as yet unknown mechanism.
Topics: Acylation; Anaerobiosis; Animals; Clostridium beijerinckii; Dihydroxyacetone Phosphate; Plasmalogens
PubMed: 28617934
DOI: 10.1002/1873-3468.12714 -
Journal of Oleo Science 2014In this study, we investigated the laboratory-scale preparation and characteristics of ethanolamine plasmalogen from marine invertebrates. The preparation method...
In this study, we investigated the laboratory-scale preparation and characteristics of ethanolamine plasmalogen from marine invertebrates. The preparation method consists of fractionation by acetone and ether treatment, and separation using column chromatography with silica gel and different eluents. Plasmalogen fractions (Pls fraction) were obtained from the viscera of the ascidian Halocynthia roretzi, and the prominent fatty acids were present as 20:5 (33.0%) and 22:6 (29.6%) n-3 polyunsaturated fatty acids (PUFA). The plasmalogen purity was 40%, and the alkenyl chains consisted of 18:0 (86.1%), 16:0 (5.9%) and 18:1 (4.9%). Precursor ion scanning in negative and positive ion modes using liquid chromatography tandem mass spectrometry (LC-MS/MS) enabled the profiling of phosphatidylethanolamine (PE) molecular species in ascidian viscera. Following LC-MS/MS with multiple reaction monitoring (MRM), the prominent plasmalogen species were found to be 18:0p/20:5 (30.4%) and 18:0p/22:6 (24.6%) (p at sn-1 position indicates alkenyl linkage). In conclusion, this preparative procedure using ascidian viscera as a source achieved 40% pure plasmalogen that was rich in n-3 PUFA. In addition, an LC-MS/MS assay enabled rapid analysis of plasmalogen species with selectivity and sensitivity. The present results will contribute to the understanding of dietary plasmalogen absorption and metabolism.
Topics: Acetone; Animals; Chemical Fractionation; Chromatography, Liquid; Ether; Fatty Acids, Omega-3; Phosphatidylethanolamines; Plasmalogens; Sensitivity and Specificity; Silica Gel; Tandem Mass Spectrometry; Urochordata
PubMed: 24717546
DOI: 10.5650/jos.ess13188