| First Author | Bradley RM | Year | 2017 |
| Journal | Mol Cell Biol | Volume | 37 |
| Issue | 22 | PubMed ID | 28807933 |
| Mgi Jnum | J:248933 | Mgi Id | MGI:6093518 |
| Doi | 10.1128/MCB.00245-17 | Citation | Bradley RM, et al. (2017) Mice Deficient in lysophosphatidic acid acyltransferase delta (Lpaatdelta)/acylglycerophosphate acyltransferase 4 (Agpat4) Have Impaired Learning and Memory. Mol Cell Biol 37(22) |
| abstractText | We previously characterized LPAATdelta/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here, we report that Lpaatdelta(-/-) 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 Lpaatdelta(-/-) mice was unchanged. Importantly, we found that Lpaatdelta(-/-) 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 alpha-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 Lpaatdelta deficiency causes deficits in learning and memory associated with reduced NMDA and AMPA receptors. |
