Heterozygous knockout of cytosolic phospholipase A2α attenuates Alzheimer's disease pathology in APP/PS1 transgenic mice

Baoxi Qu; Yunhua Gong; Jassica M Gill; Kimbra Kenney; Ramon Diaz-Arrastia

doi:10.1016/j.brainres.2017.06.021

Heterozygous knockout of cytosolic phospholipase A_2α attenuates Alzheimer's disease pathology in APP/PS1 transgenic mice

Brain Res. 2017 Sep 1:1670:248-252. doi: 10.1016/j.brainres.2017.06.021. Epub 2017 Jun 23.

Authors

Baoxi Qu¹, Yunhua Gong², Jassica M Gill³, Kimbra Kenney², Ramon Diaz-Arrastia²

Affiliations

¹ Center for Neuroscience and Regenerative Medicine, Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States. Electronic address: [email protected].
² Center for Neuroscience and Regenerative Medicine, Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
³ Tissue Injury Branch, NIH, Bethesda, MD, United States.

PMID: 28648388
DOI: 10.1016/j.brainres.2017.06.021

Abstract

Cytosolic phospholipase A2α (cPLA2α) is a key enzyme in regulation of inflammation process and neuromembrane homeostasis, both of which are critical in pathogenesis of Alzheimer's diseases. By hybride APP/PS1 Tg-AD mice with cPLA2α knockout mice, three lines of APP/PS1 Tg-AD mice were produced with genotypes of cPLA2α^+/+, cPLA2α^+/- and cPLA2α^-/-. Compared to cPLA2α^+/+ Tg-AD mice, the amyloid plaque formation was significantly downregulated in the brain of cPLA2α^+/- Tg-AD mice, but not in cPLA2α^-/- Tg-AD mice. The reactive gliosis were also significantly downregulated in both cPLA2α^+/- and cPLA2α^-/- Tg-AD mouse lines. The paradoxical effects of cPLA2α on the amyloid plaques reveal a complex role of cPLA2α in pathogenesis of AD and could be a potential target for prevention and treatment of AD.

Keywords: APPswe/PS1 transgenic mouse; Alzheimer’s disease; Cytosolic phospholipase A2; Knockout mouse; cPLA2.

Published by Elsevier B.V.

MeSH terms

Alzheimer Disease / enzymology*
Alzheimer Disease / genetics*
Alzheimer Disease / metabolism
Alzheimer Disease / pathology
Amyloid beta-Peptides / genetics
Amyloid beta-Peptides / metabolism
Amyloid beta-Protein Precursor / biosynthesis
Amyloid beta-Protein Precursor / genetics
Animals
Brain / metabolism
Cell Membrane / physiology
Cytosol / enzymology
Cytosol / metabolism
Disease Models, Animal
Glial Fibrillary Acidic Protein / biosynthesis
Glial Fibrillary Acidic Protein / genetics
Gliosis / genetics
Gliosis / metabolism
Group IV Phospholipases A2 / deficiency*
Group IV Phospholipases A2 / genetics*
Group IV Phospholipases A2 / metabolism
Heterozygote
Humans
Mice
Mice, Knockout
Mice, Transgenic
Microglia / enzymology
Microglia / metabolism
Microglia / pathology
Plaque, Amyloid / genetics
Plaque, Amyloid / metabolism
Plaque, Amyloid / pathology
Presenilin-1 / biosynthesis
Presenilin-1 / genetics

Substances

APP protein, human
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Glial Fibrillary Acidic Protein
Presenilin-1
Group IV Phospholipases A2