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

Abul Kalam Azad,Yuchi Zhang,Abdullah Md Sheikh,Md Ahsanul Haque,Hiromichi Sakai,Shahdat Hossain,Shozo Yano,Harumi Osago,Abu Zaffar Shibly,Atsushi Nagai,Xiaojing Zhou,Makoto Michikawa,Shatera Tabassum,Garu A

doi:10.3390/brainsci11121603

Abstract

Plasmalogens are alkenyl-acyl glycerophospholipids and decreased in post-mortem Alzheimer’s disease (AD) brains. The aim of this study is to investigate the time-dependent changes of plasmalogens in the hippocampus of an AD model mouse (J20). Plasmalogen levels at 3, 6, 9, 12 and 15 months were analyzed by liquid-chromatography-targeted-multiplexed-selected-reaction-monitoring-tandem-mass-spectrometry (LC-SRM/MS). Reactive oxygen species (ROS) levels were evaluated using dichlorofluorescein diacetate (DCF-DA). Plasmalogen synthesizing enzyme glycerone-phosphate O-acyltransferase (GNPAT) and late endosome marker Rab7 levels were quantified by Western blotting. GNPAT localization, changes of neuronal and glial cell numbers were evaluated by immunostaining. Compared to wild-type mice (WT), total plasmalogen-ethanolamine, but not plasmalogen-choline levels, were increased at 9 months and subsequently decreased at 15 months in J20 mice. A principal component analysis of plasmalogen-ethanolamine species could separate WT and J20 mice both at 9 and 15 months. Both GNPAT and Rab7 protein were increased in J20 mice at 9 months, whereas GNPAT was decreased at 15 months. ROS levels were increased in J20 mice except for 9 months. Our results suggest that increased plasmalogen-ethanolamine could counteract ROS levels and contribute to the phagocytosis process in J20 mice at 9 months. Such results might indicate a transient protective response of plasmalogen-ethanolamine in AD conditions.

Highlights

Plasmalogens (Pls) are a subclass of glycerophospholipids, containing fatty alcohol at the sn-1 and fatty acid at the sn-2 positions of their glycerol backbone [1]
Densitometric analysis showed that glycerone-phosphate Oacyltransferase (GNPAT) expression was increased at 9 months and subsequently decreased at 15 months in J20 mice compared to wild-type mice (WT)
The results showed that reactive oxygen species (ROS) levels were increased at 3, 6, 12, and 15 months in J20 mice compared to WT, whereas no change was found at 9 months in J20 mice (Figure 5C)

Summary

Introduction

Plasmalogens (Pls) are a subclass of glycerophospholipids, containing fatty alcohol at the sn-1 and fatty acid at the sn-2 positions of their glycerol backbone [1]. Due to the presence of a vinyl ether bond, Pls can act as an antioxidant [2]. The content of Pls determines the physiochemical properties, such as the fluidity of the cell membrane, which is important for diverse cellular functions, including ion transport regulation, membrane enzyme activities, receptor-mediated signaling, and membrane fusion during phagocytosis, endocytosis, exocytosis, and synaptic transmission [1–7]. Pls-PE facilitates the fusion processes required for sealing the membrane to form the phagosome [8]. A late endosomal protein, is required for the formation and maturation of the phagolysosome by fusion between late endosomal vesicles and lysosomal vesicles [9,10], indicating the possibility of an association between Pls-PE and Rab change. The role of Pls level change in the pathology of these diseases remained unknown [1]

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