Affiliation:
1. University of Waterloo, Department of Kinesiology, Faculty of Applied Health Sciences, Waterloo, Ontario, Canada
Abstract
ABSTRACT
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here, we report that
Lpaat
δ
−/−
mice display impaired spatial learning and memory compared to wild-type littermates in the Morris water maze and our investigation of potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged. Relative abundance of the important brain fatty acid docosahexaenoic acid was also unchanged in phosphatidylserine, phosphatidylglycerol, and cardiolipin, in agreement with prior data on PC, PE and PI. In phosphatidic acid, it was increased. Specific decreases in ethanolamine-containing phospholipids were detected in mitochondrial lipids, but the function of brain mitochondria in
Lpaat
δ
−/−
mice was unchanged. Importantly, we found that
Lpaat
δ
−/−
mice have a significantly and drastically lower brain content of the
N
-methyl-
d
-asparate (NMDA) receptor subunits NR1, NR2A, and NR2B, as well as the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1, compared to wild-type mice. However, general dysregulation of PI-mediated signaling is not likely responsible, since phospho-AKT and phospho-mTOR pathway regulation was unaffected. Our findings indicate that
Lpaat
δ deficiency causes deficits in learning and memory associated with reduced NMDA and AMPA receptors.
Funder
Ontario Ministry of Research, Innovation, and Science
Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada
Canada Foundation for Innovation
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology