Time-Dependent Analysis of Plasmalogens in the Hippocampus of an Alzheimer’s Disease Mouse Model: A Role of Ethanolamine Plasmalogen

Азад, Абул Калам; Sheikh, Abdullah Md.; Haque, Ahsanul; Osago, Harumi; Sakai, Hiromichi; Shibly, Abu Zaffar; Yano, Shozo; Michikawa, Makoto; Hossain, Shahdat; Tabassum, Shatera; Garu, A; Zhou, Xiaojing; Zhang, Yuchi; Nagai, Atsushi

doi:10.3390/brainsci11121603

Cited by 9 publications

(8 citation statements)

References 52 publications

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“…Second, most of these studies were conducted on the whole brain 32 , 35 with few having assessed specific brain areas (e.g. hippocampus 24 , 36 , cortex 34 , 37 ), it would therefore be interesting to consider other areas simultaneously. Third, the mice age ranged from 2 to 24 months 28 , 38 .…”

Section: Introductionmentioning

confidence: 99%

Brain areas lipidomics in female transgenic mouse model of Alzheimer's disease

Ferré-González,

Balaguer,

Roca

et al. 2024

Sci Rep

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Lipids are the major component of the brain with important structural and functional properties. Lipid disruption could play a relevant role in Alzheimer’s disease (AD). Some brain lipidomic studies showed significant differences compared to controls, but few studies have focused on different brain areas related to AD. Furthermore, AD is more prevalent in females, but there is a lack of studies focusing on this sex. This work aims to perform a lipidomic study in selected brain areas (cerebellum, amygdala, hippocampus, entire cortex) from wild-type (WT, n = 10) and APPswe/PS1dE9 transgenic (TG, n = 10) female mice of 5 months of age, as a model of early AD, to identify alterations in lipid composition. A lipidomic mass spectrometry-based method was optimized and applied to brain tissue. As result, some lipids showed statistically significant differences between mice groups in cerebellum (n = 68), amygdala (n = 49), hippocampus (n = 48), and the cortex (n = 22). In addition, some lipids (n = 15) from the glycerolipid, phospholipid, and sphingolipid families were statistically significant in several brain areas simultaneously between WT and TG. A selection of lipid variables was made to develop a multivariate approach to assess their discriminant potential, showing high diagnostic indexes, especially in cerebellum and amygdala (sensitivity 70–100%, sensibility 80–100%).

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Section: Introductionmentioning

confidence: 99%

Brain areas lipidomics in female transgenic mouse model of Alzheimer's disease

Ferré-González,

Balaguer,

Roca

et al. 2024

Sci Rep

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“…Importantly, plasmalogens can protect lipid bilayers against the damaging effects of oxidation by scavenger radicals, such as ROS and reactive nitrogen species. As such, decreased plasmalogen concentrations may increase one's susceptibility to developing neurodegenerative or neuroinflammatory disorders, such as Alzheimer's disease (Azad et al., 2021; Han et al., 2001), Parkison's disease, or MS (Ferreira et al., 2021; Mawatari et al., 2020). Here, we demonstrate that FTY720 increases plasmenyl‐PE levels from 17.0% to 20.5% of the total lipid composition of the mouse hippocampus, which may increase the resistance of vulnerable neurons to oxidative stress (Zoeller et al., 2002) and explain why other studies have found that FTY720 can reverse cognitive deficits in animal models of CNS diseases (Fagan et al., 2022; Udagawa & Hino, 2022).…”

Section: Discussionmentioning

confidence: 99%

The sphingosine 1‐phosphate analogue, FTY720, modulates the lipidomic signature of the mouse hippocampus

Magalhães,

Stewart,

Mampay

et al. 2024

Journal of Neurochemistry

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The small‐molecule drug, FTY720 (fingolimod), is a synthetic sphingosine 1‐phosphate (S1P) analogue currently used to treat relapsing–remitting multiple sclerosis in both adults and children. FTY720 can cross the blood–brain barrier (BBB) and, over time, accumulate in lipid‐rich areas of the central nervous system (CNS) by incorporating into phospholipid membranes. FTY720 has been shown to enhance cell membrane fluidity, which can modulate the functions of glial cells and neuronal populations involved in regulating behaviour. Moreover, direct modulation of S1P receptor‐mediated lipid signalling by FTY720 can impact homeostatic CNS physiology, including neurotransmitter release probability, the biophysical properties of synaptic membranes, ion channel and transmembrane receptor kinetics, and synaptic plasticity mechanisms. The aim of this study was to investigate how chronic FTY720 treatment alters the lipid composition of CNS tissue in adolescent mice at a key stage of brain maturation. We focused on the hippocampus, a brain region known to be important for learning, memory, and the processing of sensory and emotional stimuli. Using mass spectrometry‐based lipidomics, we discovered that FTY720 increases the fatty acid chain length of hydroxy‐phosphatidylcholine (PCOH) lipids in the mouse hippocampus. It also decreases PCOH monounsaturated fatty acids (MUFAs) and increases PCOH polyunsaturated fatty acids (PUFAs). A total of 99 lipid species were up‐regulated in the mouse hippocampus following 3 weeks of oral FTY720 exposure, whereas only 3 lipid species were down‐regulated. FTY720 also modulated anxiety‐like behaviours in young mice but did not affect spatial learning or memory formation. Our study presents a comprehensive overview of the lipid classes and lipid species that are altered in the hippocampus following chronic FTY720 exposure and provides novel insight into cellular and molecular mechanisms that may underlie the therapeutic or adverse effects of FTY720 in the central nervous system.

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“…These results are in line with literature, consistently showing a decrease in plasmalogen levels in different brain regions or CSFs in AD patients [ 26 , 48 , 68 , 69 , 70 , 71 , 72 , 73 ]. Furthermore, reduced plasmalogen levels can be found in AD mouse models [ 74 , 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells

Theiss

Griebsch

Lauer

et al. 2022

Cells

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Oxidative stress is closely linked to Alzheimer’s disease (AD), and is detected peripherally as well as in AD-vulnerable brain regions. Oxidative stress results from an imbalance between the generation and degradation of reactive oxidative species (ROS), leading to the oxidation of proteins, nucleic acids, and lipids. Extensive lipid changes have been found in post mortem AD brain tissue; these changes include the levels of total phospholipids, sphingomyelin, and ceramide, as well as plasmalogens, which are highly susceptible to oxidation because of their vinyl ether bond at the sn-1 position of the glycerol-backbone. Several lines of evidence indicate that a deficiency in the neurotropic vitamin B12 is linked with AD. In the present study, treatment of the neuroblastoma cell line SH-SY5Y with vitamin B12 resulted in elevated levels of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and plasmalogens. Vitamin B12 also protected plasmalogens from hydrogen peroxide (H2O2)-induced oxidative stress due to an elevated expression of the ROS-degrading enzymes superoxide-dismutase (SOD) and catalase (CAT). Furthermore, vitamin B12 elevates plasmalogen synthesis by increasing the expression of alkylglycerone phosphate synthase (AGPS) and choline phosphotransferase 1 (CHPT1) in SH-SY5Y cells exposed to H2O2-induced oxidative stress.

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Time-Dependent Analysis of Plasmalogens in the Hippocampus of an Alzheimer’s Disease Mouse Model: A Role of Ethanolamine Plasmalogen

Cited by 9 publications

References 52 publications

Brain areas lipidomics in female transgenic mouse model of Alzheimer's disease

Brain areas lipidomics in female transgenic mouse model of Alzheimer's disease

The sphingosine 1‐phosphate analogue, FTY720, modulates the lipidomic signature of the mouse hippocampus

Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells

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