Mice Deficient in lysophosphatidic acid acyltransferase delta (Lpaatδ)/acylglycerophosphate acyltransferase 4 (Agpat4) Have Impaired Learning and Memory

REFERENCES

• Kennedy EP, Weiss SB. 1956. The function of cytidine coenzymes in the biosynthesis of phospholipids. J Biol Chem 222:193–214.
   PubMed Web of Science ®Google Scholar
• Yamashita A, Hayashi Y, Matsumoto N, Nemoto-Sasaki Y, Oka S, Tanikawa T, Sugiura T. 2014. Glycerophosphate/acylglycerophosphate acyltransferases. Biology 3:801–830. https://doi.org/10.3390/biology3040801.
   PubMedGoogle Scholar
• Kitson AP, Stark KD, Duncan RE. 2012. Enzymes in brain phospholipid docosahexaenoic acid accretion: a PL-ethora of potential PL-ayers. Prostaglandins Leukot Essent Fatty Acids 87:1–10. https://doi.org/10.1016/j.plefa.2012.06.001.
   PubMedGoogle Scholar
• Bradley RM, Mardian EB, Moes KA, Duncan RE. 2017. Acute fasting induces expression of acylglycerophosphate acyltransferase (AGPAT) enzymes in murine liver, heart, and brain. Lipids 52:457–461. https://doi.org/10.1007/s11745-017-4251-4.
   PubMedGoogle Scholar
• Bradley RM, Mardian EB, Marvyn PM, Vasefi MS, Beazely MA, Mielke JG, Duncan RE. 2016. Data on acylglycerophosphate acyltransferase 4 (AGPAT4) during murine embryogenesis and in embryo-derived cultured primary neurons and glia. Data Brief 6:28–32. https://doi.org/10.1016/j.dib.2015.11.033.
   PubMedGoogle Scholar
• Bradley RM, Marvyn PM, Aristizabal Henao JJ, Mardian EB, George S, Aucoin MG, Stark KD, Duncan RE. 2015. Acylglycerophosphate acyltransferase 4 (AGPAT4) is a mitochondrial lysophosphatidic acid acyltransferase that regulates brain phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol levels. Biochim Biophys Acta 1851:1566–1576. https://doi.org/10.1016/j.bbalip.2015.09.005.
   PubMedGoogle Scholar
• Eto M, Shindou H, Shimizu T. 2014. A novel lysophosphatidic acid acyltransferase enzyme (LPAAT4) with a possible role for incorporating docosahexaenoic acid into brain glycerophospholipids. Biochem Biophys Res Commun 443:718–724. https://doi.org/10.1016/j.bbrc.2013.12.043.
   PubMedGoogle Scholar
• Daum G. 1985. Lipids of mitochondria. Biochim Biophys Acta 822:1–42. https://doi.org/10.1016/0304-4157(85)90002-4.
   PubMed Web of Science ®Google Scholar
• Diagne A, Fauvel J, Record M, Chap H, Douste-Blazy L. 1984. Studies on ether phospholipids. II. Comparative composition of various tissues from human, rat and guinea pig. Biochim Biophys Acta 793:221–231.
   PubMedGoogle Scholar
• Modi HR, Katyare SS, Patel MA. 2008. Ageing-induced alterations in lipid/phospholipid profiles of rat brain and liver mitochondria: implications for mitochondrial energy-linked functions. J Membr Biol 221:51–60. https://doi.org/10.1007/s00232-007-9086-0.
   PubMedGoogle Scholar
• Zhang Y, McCartney AJ, Zolov SN, Ferguson CJ, Meisler MH, Sutton MA, Weisman LS. 2012. Modulation of synaptic function by VAC14, a protein that regulates the phosphoinositides PI(3,5)P(2) and PI(5)P. EMBO J 31:3442–3456. https://doi.org/10.1038/emboj.2012.200.
   PubMed Web of Science ®Google Scholar
• Vicinanza M, D'Angelo G, Di Campli A, De Matteis MA. 2008. Function and dysfunction of the PI system in membrane trafficking. EMBO J 27:2457–2470. https://doi.org/10.1038/emboj.2008.169.
   PubMedGoogle Scholar
• Ueno T, Falkenburger BH, Pohlmeyer C, Inoue T. 2011. Triggering actin comets versus membrane ruffles: distinctive effects of phosphoinositides on actin reorganization. Sci Signal 4:ra87. https://doi.org/10.1126/scisignal.2002033.
   PubMedGoogle Scholar
• Sanna PP, Cammalleri M, Berton F, Simpson C, Lutjens R, Bloom FE, Francesconi W. 2002. Phosphatidylinositol 3-kinase is required for the expression but not for the induction or the maintenance of long-term potentiation in the hippocampal CA1 region. J Neurosci 22:3359–3365.
   PubMed Web of Science ®Google Scholar
• Arendt KL, Royo M, Fernandez-Monreal M, Knafo S, Petrok CN, Martens JR, Esteban JA. 2010. PIP3 controls synaptic function by maintaining AMPA receptor clustering at the postsynaptic membrane. Nat Neurosci 13:36–44. https://doi.org/10.1038/nn.2462.
   PubMedGoogle Scholar
• Wells K, Farooqui AA, Liss L, Horrocks LA. 1995. Neural membrane phospholipids in Alzheimer disease. Neurochem Res 20:1329–1333. https://doi.org/10.1007/BF00992508.
   PubMed Web of Science ®Google Scholar
• Lim SY, Suzuki H. 2008. Dietary phosphatidylcholine improves maze-learning performance in adult mice. J Med Food 11:86–90. https://doi.org/10.1089/jmf.2007.060.
   PubMedGoogle Scholar
• Zeisel SH. 2006. Choline: critical role during fetal development and dietary requirements in adults. Annu Rev Nutr 26:229–250. https://doi.org/10.1146/annurev.nutr.26.061505.111156.
   PubMed Web of Science ®Google Scholar
• Zeisel SH. 1992. Choline: an important nutrient in brain development, liver function and carcinogenesis. J Am Coll Nutr 11:473–481. https://doi.org/10.1080/07315724.1992.10718251.
   PubMed Web of Science ®Google Scholar
• Kubo K, Saito M, Tadokoro T, Maekawa A. 2000. Preferential incorporation of docosahexaenoic acid into nonphosphorus lipids and phosphatidylethanolamine protects rats from dietary DHA-stimulated lipid peroxidation. J Nutr 130:1749–1759.
   PubMed Web of Science ®Google Scholar
• Sastry PS. 1985. Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 24:69–176. https://doi.org/10.1016/0163-7827(85)90011-6.
   PubMed Web of Science ®Google Scholar
• Mita T, Mayanagi T, Ichijo H, Fukumoto K, Otsuka K, Sakai A, Sobue K. 2016. Docosahexaenoic acid promotes axon outgrowth by translational regulation of Tau and collapsin response mediator protein 2 expression. J Biol Chem 291:4955–4965. https://doi.org/10.1074/jbc.M115.693499.
   PubMed Web of Science ®Google Scholar
• Cao D, Kevala K, Kim J, Moon HS, Jun SB, Lovinger D, Kim HY. 2009. Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J Neurochem 111:510–521. https://doi.org/10.1111/j.1471-4159.2009.06335.x.
   PubMed Web of Science ®Google Scholar
• Su HM. 2010. Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance. J Nutr Biochem 21:364–373. https://doi.org/10.1016/j.jnutbio.2009.11.003.
   PubMed Web of Science ®Google Scholar
• Gamoh S, Hashimoto M, Sugioka K, Shahdat Hossain M, Hata N, Misawa Y, Masumura S. 1999. Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats. Neuroscience 93:237–241. https://doi.org/10.1016/S0306-4522(99)00107-4.
   PubMed Web of Science ®Google Scholar
• Petursdottir AL, Farr SA, Morley JE, Banks WA, Skuladottir GV. 2008. Effect of dietary n-3 polyunsaturated fatty acids on brain lipid fatty acid composition, learning ability, and memory of senescence-accelerated mouse. J Gerontol A Biol Sci Med Sci 63:1153–1160. https://doi.org/10.1093/gerona/63.11.1153.
   PubMed Web of Science ®Google Scholar
• Xiao Y, Wang L, Xu R, Chen Z. 2006. DHA depletion in rat brain is associated with impairment on spatial learning and memory. Biomed Environ Sci 19:474.
   PubMedGoogle Scholar
• Cao X, Cui Z, Feng R, Tang YP, Qin Z, Mei B, Tsien JZ. 2007. Maintenance of superior learning and memory function in NR2B transgenic mice during ageing. Eur J Neurosci 25:1815–1822. https://doi.org/10.1111/j.1460-9568.2007.05431.x.
   PubMedGoogle Scholar
• Ng D, Pitcher GM, Szilard RK, Sertie A, Kanisek M, Clapcote SJ, Lipina T, Kalia LV, Joo D, McKerlie C, Cortez M, Roder JC, Salter MW, McInnes RR. 2009. Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning. PLoS Biol 7:e41. https://doi.org/10.1371/journal.pbio.1000041.
   Google Scholar
• Lopez J, Gamache K, Schneider R, Nader K. 2015. Memory retrieval requires ongoing protein synthesis and NMDA receptor activity-mediated AMPA receptor trafficking. J Neurosci 35:2465–2475. https://doi.org/10.1523/JNEUROSCI.0735-14.2015.
   PubMedGoogle Scholar
• Morris RG, Steele RJ, Bell JE, Martin SJ. 2013. N-methyl-d-aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d-AP5 interacts directly with the neural mechanisms of spatial learning. Eur J Neurosci 37:700–717. https://doi.org/10.1111/ejn.12086.
   PubMed Web of Science ®Google Scholar
• Michailidis IE, Helton TD, Petrou VI, Mirshahi T, Ehlers MD, Logothetis DE. 2007. Phosphatidylinositol-4,5-bisphosphate regulates NMDA receptor activity through alpha-actinin. J Neurosci 27:5523–5532. https://doi.org/10.1523/JNEUROSCI.4378-06.2007.
   PubMedGoogle Scholar
• Mandal M, Yan Z. 2009. Phosphatidylinositol (4,5)-bisphosphate regulation of N-methyl-d-aspartate receptor channels in cortical neurons. Mol Pharmacol 76:1349–1359. https://doi.org/10.1124/mol.109.058701.
   PubMedGoogle Scholar
• Heras-Sandoval D, Perez-Rojas JM, Hernandez-Damian J, Pedraza-Chaverri J. 2014. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal 26:2694–2701. https://doi.org/10.1016/j.cellsig.2014.08.019.
   PubMed Web of Science ®Google Scholar
• Norrmen C, Suter U. 2013. Akt/mTOR signalling in myelination. Biochem Soc Trans 41:944–950. https://doi.org/10.1042/BST20130046.
   PubMed Web of Science ®Google Scholar
• Ahn JY. 2014. Neuroprotection signaling of nuclear akt in neuronal cells. Exp Neurobiol 23:200–206. https://doi.org/10.5607/en.2014.23.3.200.
   PubMedGoogle Scholar
• Yang PC, Yang CH, Huang CC, Hsu KS. 2008. Phosphatidylinositol 3-kinase activation is required for stress protocol-induced modification of hippocampal synaptic plasticity. J Biol Chem 283:2631–2643. https://doi.org/10.1074/jbc.M706954200.
   PubMedGoogle Scholar
• Tao R, Gong J, Luo X, Zang M, Guo W, Wen R, Luo Z. 2010. AMPK exerts dual regulatory effects on the PI3K pathway. J Mol Signal 5:1. https://doi.org/10.1186/1750-2187-5-1.
   PubMedGoogle Scholar
• Kovacina KS, Park GY, Bae SS, Guzzetta AW, Schaefer E, Birnbaum MJ, Roth RA. 2003. Identification of a proline-rich Akt substrate as a 14-3-3 binding partner. J Biol Chem 278:10189–10194. https://doi.org/10.1074/jbc.M210837200.
   PubMed Web of Science ®Google Scholar
• Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM. 2008. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320:1496–1501. https://doi.org/10.1126/science.1157535.
   PubMed Web of Science ®Google Scholar
• Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan KL. 2008. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 10:935–945. https://doi.org/10.1038/ncb1753.
   PubMed Web of Science ®Google Scholar
• Jones JPIII, Meck HW, Williams CL, Wilson WA, Swartzwelder HS. 1999. Choline availability to the developing rat fetus alters adult hippocampal long-term potentiation. Brain Res Dev Brain Res 118:159–167. https://doi.org/10.1016/S0165-3806(99)00103-0.
   PubMedGoogle Scholar
• Cooke SF, Bliss TV. 2006. Plasticity in the human central nervous system. Brain 129:1659–1673. https://doi.org/10.1093/brain/awl082.
   PubMed Web of Science ®Google Scholar
• Bliss TV, Collingridge GL. 1993. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39. https://doi.org/10.1038/361031a0.
   PubMed Web of Science ®Google Scholar
• Witcher MR, Kirov SA, Harris KM. 2007. Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampus. Glia 55:13–23. https://doi.org/10.1002/glia.20415.
   PubMedGoogle Scholar
• Stubbs CD, Smith AD. 1984. The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim Biophys Acta 779:89–137. https://doi.org/10.1016/0304-4157(84)90005-4.
   PubMed Web of Science ®Google Scholar
• Bradley RM, Stark KD, Duncan RE. 2016. Influence of tissue, diet, and enzymatic remodeling on cardiolipin fatty acyl profile. Mol Nutr Food Res 60:1804–1818. https://doi.org/10.1002/mnfr.201500966.
   PubMedGoogle Scholar
• Hancock SE, Friedrich MG, Mitchell TW, Truscott RJ, Else PL. 2015. Decreases in phospholipids containing adrenic and arachidonic acids occur in the human hippocampus over the adult lifespan. Lipids 50:861–872. https://doi.org/10.1007/s11745-015-4030-z.
   PubMedGoogle Scholar
• Norris SE, Friedrich MG, Mitchell TW, Truscott RJ, Else PL. 2015. Human prefrontal cortex phospholipids containing docosahexaenoic acid increase during normal adult aging, whereas those containing arachidonic acid decrease. Neurobiol Aging 36:1659–1669. https://doi.org/10.1016/j.neurobiolaging.2015.01.002.
   PubMed Web of Science ®Google Scholar
• de Groot RH, Hornstra G, Jolles J. 2007. Exploratory study into the relation between plasma phospholipid fatty acid status and cognitive performance. Prostaglandins Leukot Essent Fatty Acids 76:165–172. https://doi.org/10.1016/j.plefa.2007.01.001.
   PubMedGoogle Scholar
• Sumich AL, Matsudaira T, Heasman B, Gow RV, Ibrahimovic A, Ghebremeskel K, Crawford MA, Taylor E. 2013. Fatty acid correlates of temperament in adolescent boys with attention deficit hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids 88:431–436. https://doi.org/10.1016/j.plefa.2013.03.004.
   PubMedGoogle Scholar
• Yui K, Imataka G, Kawasaki Y, Yamada H. 2016. Increased omega-3 polyunsaturated fatty acid/arachidonic acid ratios and upregulation of signaling mediator in individuals with autism spectrum disorders. Life Sci 145:205–212. https://doi.org/10.1016/j.lfs.2015.12.039.
   PubMedGoogle Scholar
• Yui K, Imataka G, Kawasaki Y, Yamada H. 2016. Down-regulation of a signaling mediator in association with lowered plasma arachidonic acid levels in individuals with autism spectrum disorders. Neurosci Lett 610:223–228. https://doi.org/10.1016/j.neulet.2015.11.006.
   PubMedGoogle Scholar
• Chen HC, Ziemba BP, Landgraf KE, Corbin JA, Falke JJ. 2012. Membrane docking geometry of GRP1 PH domain bound to a target lipid bilayer: an EPR site-directed spin-labeling and relaxation study. PLoS One 7:e33640. https://doi.org/10.1371/journal.pone.0033640.
   Google Scholar
• Rhee SG, Choi KD. 1992. Regulation of inositol phospholipid-specific phospholipase C isozymes. J Biol Chem 267:12393–12396.
   PubMed Web of Science ®Google Scholar
• Groc L, Choquet D. 2006. AMPA and NMDA glutamate receptor trafficking: multiple roads for reaching and leaving the synapse. Cell Tissue Res 326:423–438. https://doi.org/10.1007/s00441-006-0254-9.
   PubMed Web of Science ®Google Scholar
• Kim R, Moki R, Kida S. 2011. Molecular mechanisms for the destabilization and restabilization of reactivated spatial memory in the Morris water maze. Mol Brain 4:9. https://doi.org/10.1186/1756-6606-4-9.
   PubMed Web of Science ®Google Scholar
• Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E, Yagi T, Aizawa S, Inoue Y, Sugiyama H. 1995. Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor 1 subunit. Nature 373:151–154. https://doi.org/10.1038/373151a0.
   PubMed Web of Science ®Google Scholar
• Park P, Sanderson TM, Amici M, Choi SL, Bortolotto ZA, Zhuo M, Kaang BK, Collingridge GL. 2016. Calcium-permeable AMPA receptors mediate the induction of the protein kinase A-dependent component of long-term potentiation in the hippocampus. J Neurosci 36:622–631. https://doi.org/10.1523/JNEUROSCI.3625-15.2016.
   PubMedGoogle Scholar
• Zamanillo D, Sprengel R, Hvalby Ø, Jensen V, Burnashev N, Rozov A, Kaiser KMM, Köster HJ, Borchardt T, Worley P, Lübke J, Frotscher M, Kelly PH, Sommer B, Andersen P, Seeburg PH, Sakmann B. 1999. Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 284:1805–1811. https://doi.org/10.1126/science.284.5421.1805.
   PubMed Web of Science ®Google Scholar
• Malhotra AK, Pinals DA, Weingartner H, Sirocco K, David Missar C, Pickar D, Breier A. 1996. NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology 14:301–307. https://doi.org/10.1016/0893-133X(95)00137-3.
   PubMed Web of Science ®Google Scholar
• Furukawa H, Singh SK, Mancusso R, Gouaux E. 2005. Subunit arrangement and function in NMDA receptors. Nature 438:185–192. https://doi.org/10.1038/nature04089.
   PubMed Web of Science ®Google Scholar
• Dyall SC, Michael GJ, Whelpton R, Scott AG, Michael-Titus AT. 2007. Dietary enrichment with omega-3 polyunsaturated fatty acids reverses age-related decreases in the GluR2 and NR2B glutamate receptor subunits in rat forebrain. Neurobiol Aging 28:424–439. https://doi.org/10.1016/j.neurobiolaging.2006.01.002.
   PubMed Web of Science ®Google Scholar
• Miao B, Skidan I, Yang J, Lugovskoy A, Reibarkh M, Long K, Brazell T, Durugkar KA, Maki J, Ramana CV, Schaffhausen B, Wagner G, Torchilin V, Yuan J, Degterev A. 2010. Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains. Proc Natl Acad Sci U S A 107:20126–20131. https://doi.org/10.1073/pnas.1004522107.
   PubMed Web of Science ®Google Scholar
• Mendoza MC, Er EE, Blenis J. 2011. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci 36:320–328. https://doi.org/10.1016/j.tibs.2011.03.006.
   PubMed Web of Science ®Google Scholar
• Sengupta S, Peterson TR, Sabatini DM. 2010. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 40:310–322. https://doi.org/10.1016/j.molcel.2010.09.026.
   PubMed Web of Science ®Google Scholar
• Kim SY, Yoo SJ, Ronnett GV, Kim EK, Moon C. 2015. Odorant stimulation promotes survival of rodent olfactory receptor neurons via PI3K/Akt activation and Bcl-2 expression. Mol Cells 38:535–539. https://doi.org/10.14348/molcells.2015.0038.
   PubMedGoogle Scholar
• Le Belle JE, Orozco NM, Paucar AA, Saxe JP, Mottahedeh J, Pyle AD, Wu H, Kornblum HI. 2011. Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependent manner. Cell Stem Cell 8:59–71. https://doi.org/10.1016/j.stem.2010.11.028.
   PubMed Web of Science ®Google Scholar
• Rathmell JC, Fox CJ, Plas DR, Hammerman PS, Cinalli RM, Thompson CB. 2003. Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival. Mol Cell Biol 23:7315–7328. https://doi.org/10.1128/MCB.23.20.7315-7328.2003.
   PubMed Web of Science ®Google Scholar
• Akama KT, McEwen BS. 2003. Estrogen stimulates postsynaptic density-95 rapid protein synthesis via the Akt/protein kinase B pathway. J Neurosci 23:2333–2339.
   PubMed Web of Science ®Google Scholar
• Bergeron R, Russell RR, Young LH, Ren J-M, Marcucci M, Lee A, Shulman GI. 1999. Effect of AMPK activation on muscle glucose metabolism in conscious rats. Am J Physiol 276:E938–E944.
   PubMed Web of Science ®Google Scholar
• Cota D, Proulx K, Smith KAB, Kozma SC, Thomas G, Woods SC, Seeley RJ. 2006. Hypothalamic mTOR signaling regulates food intake. Science 312:927–930. https://doi.org/10.1126/science.1124147.
   PubMed Web of Science ®Google Scholar
• Chen J, Fujii K, Zhang L, Roberts T, Fu H. 2001. Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK–ERK independent mechanism. Proc Natl Acad Sci U S A 98:7783–7788. https://doi.org/10.1073/pnas.141224398.
   PubMed Web of Science ®Google Scholar
• Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, Sedivy JM, Kolch W. 2000. Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Mol Cell Biol 20:3079–3085. https://doi.org/10.1128/MCB.20.9.3079-3085.2000.
   PubMed Web of Science ®Google Scholar
• English JM, Pearson G, Hockenberry T, Shivakumar L, White MA, Cobb MH. 1999. Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control. J Biol Chem 274:31588–31592. https://doi.org/10.1074/jbc.274.44.31588.
   PubMed Web of Science ®Google Scholar
• Zang M, Hayne C, Luo Z. 2002. Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1. J Biol Chem 277:4395–4405. https://doi.org/10.1074/jbc.M110000200.
   PubMedGoogle Scholar
• Morris R. 1984. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60. https://doi.org/10.1016/0165-0270(84)90007-4.
   PubMed Web of Science ®Google Scholar
• Vorhees CV, Williams MT. 2006. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1:848–858. https://doi.org/10.1038/nprot.2006.116.
   PubMed Web of Science ®Google Scholar
• Mardian EB, Bradley RM, Aristizabal Henao JJ, Marvyn PM, Moes KA, Bombardier E, Tupling AR, Stark KD, Duncan RE. 16August2017. Agpat4/Lpaatδ deficiency highlights the molecular heterogeneity of epididymal and perirenal white adipose depots. J Lipid Res. https://doi.org/10.1194/jlr.M079152.
   Google Scholar
• Tang T, Li L, Tang J, Li Y, Lin WY, Martin F, Grant D, Solloway M, Parker L, Ye W, Forrest W, Ghilardi N, Oravecz T, Platt KA, Rice DS, Hansen GM, Abuin A, Eberhart DE, Godowski P, Holt KH, Peterson A, Zambrowicz BP, de Sauvage FJ. 2010. A mouse knockout library for secreted and transmembrane proteins. Nat Biotechnol 28:749–755. https://doi.org/10.1038/nbt.1644.
   PubMed Web of Science ®Google Scholar
• Lewin TM, Wang P, Coleman RA. 1999. Analysis of amino acid motifs diagnostic for the sn-glycerol-3-phosphate acyltransferase reaction. Biochemistry 38:5764–5771. https://doi.org/10.1021/bi982805d.
   PubMed Web of Science ®Google Scholar
• Chen A, Bao C, Tang Y, Luo X, Guo L, Liu B, Lin C. 2015. Involvement of protein kinase zeta in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity. J Neurophysiol 113:3047–3055. https://doi.org/10.1152/jn.00929.2014.
   PubMedGoogle Scholar
• Afshordel S, Hagl S, Werner D, Rohner N, Kogel D, Bazan NG, Eckert GP. 2015. Omega-3 polyunsaturated fatty acids improve mitochondrial dysfunction in brain aging—impact of Bcl-2 and NPD-1 like metabolites. Prostaglandins Leukot Essent Fatty Acids 92:23–31. https://doi.org/10.1016/j.plefa.2014.05.008.
   PubMedGoogle Scholar
• Hagl S, Kocher A, Schiborr C, Eckert SH, Ciobanu I, Birringer M, El-Askary H, Helal A, Khayyal MT, Frank J, Muller WE, Eckert GP. 2013. Rice bran extract protects from mitochondrial dysfunction in guinea pig brains. Pharmacol Res 76:17–27. https://doi.org/10.1016/j.phrs.2013.06.008.
   PubMed Web of Science ®Google Scholar
• Krumschnabel G, Fontana-Ayoub M, Sumbalova Z, Heidler J, Gauper K, Fasching M, Gnaiger E. 2015. Simultaneous high-resolution measurement of mitochondrial respiration and hydrogen peroxide production. Methods Mol Biol 1264:245–261. https://doi.org/10.1007/978-1-4939-2257-4_22.
   PubMedGoogle Scholar
• Folch J, Lees M, Sloane Stanley GH. 1957. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509.
   PubMed Web of Science ®Google Scholar
• Metherel AH, Taha AY, Izadi H, Stark KD. 2009. The application of ultrasound energy to increase lipid extraction throughput of solid matrix samples (flaxseed). Prostaglandins Leukot Essent Fatty Acids 81:417–423. https://doi.org/10.1016/j.plefa.2009.07.003.
   PubMed Web of Science ®Google Scholar
• Graham JM, Rickwood D. (ed). 1997. Subcellular fractionation: a practical approach. Oxford University Press, New York, NY.
   Google Scholar