Anderson WW, Collingridge GL (2007) Capabilities of the WinLTP data acquisition program extending beyond basic LTP experimental functions. J Neurosci Methods 162: 346–356. doi:10.1016/j. jneumeth.2006.12.018
Araki E, Yamashita S, Arai H, Yokote K, Satoh J, Inoguchi T, Nakamura J, Maegawa H, Yoshioka N, Tanizawa Y, et al (2018) Effects of pemafibrate, a novel selective PPARalpha modulator, on lipid and glucose metabolism in patients with type 2 diabetes and hypertriglyceridemia: A randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 41: 538–546. doi:10.2337/dc17-1589
Arevalo MA, Azcoitia I, Gonzalez-Burgos I, Garcia-Segura LM (2015) Signaling mechanisms mediating the regulation of synaptic plasticity and memory by estradiol. Horm Behav 74: 19–27. doi:10.1016/j. yhbeh.2015.04.016
Barrier L, Ingrand S, Fauconneau B, Page G (2010) Gender-dependent accumulation of ceramides in the cerebral cortex of the APP(SL)/ PS1Ki mouse model of Alzheimer’s disease. Neurobiol Aging 31: 1843–1853. doi:10.1016/j.neurobiolaging.2008.10.011
Bensinger SJ, Tontonoz P (2008) Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 454: 470–477. doi:10.1038/ nature07202
Bliss TV, Collingridge GL (1993) A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 361: 31–39. doi:10.1038/ 361031a0
Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ (2006) Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 126: 789–799. doi:10.1016/j. cell.2006.06.049
Chen HJ, Rojas-Soto M, Oguni A, Kennedy MB (1998) A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II. Neuron 20: 895–904. doi:10.1016/s0896-6273(00)80471-7
Chung KW, Lee EK, Lee MK, Oh GT, Yu BP, Chung HY (2018) Impairment of PPARalpha and the fatty acid oxidation pathway aggravates renal fibrosis during aging. J Am Soc Nephrol 29: 1223–1237. doi:10.1681/ asn.2017070802
Corbett GT, Gonzalez FJ, Pahan K (2015) Activation of peroxisome proliferator-activated receptor alpha stimulates ADAM10-mediated proteolysis of APP. Proc Natl Acad Sci U S A 112: 8445–8450. doi:10.1073/ pnas.1504890112
D’Agostino G, Cristiano C, Lyons DJ, Citraro R, Russo E, Avagliano C, Russo R, Raso GM, Meli R, De SG, et al (2015) Peroxisome proliferator-activated receptor alpha plays a crucial role in behavioral repetition and cognitive flexibility in mice. Mol Metab 4: 528–536. doi:10.1016/j. molmet.2015.04.005
D’Orio B, Fracassi A, Ceru MP, Moreno S (2018) Targeting PPARalpha in Alzheimer’s disease. Curr Alzheimer Res 15: 345–354. doi:10.2174/ 1567205014666170505094549
Derkach VA, Oh MC, Guire ES, Soderling TR (2007) Regulatory mechanisms of AMPA receptors in synaptic plasticity. Nat Rev Neurosci 8: 101–113. doi:10.1038/nrn2055
Doshina A, Gourgue F, Onizuka M, Opsomer R, Wang P, Ando K, Tasiaux B, Dewachter I, Kienlen-Campard P, Brion JP, et al (2017) Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission. Sci Rep 7: 370. doi:10.1038/s41598-017-00325-2
Dotson AL, Wang J, Chen Y, Manning D, Nguyen H, Saugstad JA, Offner H (2016) Sex differences and the role of PPAR alpha in experimental stroke. Metab Brain Dis 31: 539–547. doi:10.1007/s11011-015-9766-x
Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (1997) p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha. J Biol Chem 272: 33435–33443. doi:10.1074/ jbc.272.52.33435
Evans RM, Mangelsdorf DJ (2014) Nuclear receptors, RXR, and the Big Bang. Cell 157: 255–266. doi:10.1016/j.cell.2014.03.012
Ferretti MT, Iulita MF, Cavedo E, Chiesa PA, Schumacher DA, Santuccione CA, Baracchi F, Girouard H, Misoch S, Giacobini E, et al (2018) Sex differences in Alzheimer disease: The gateway to precision medicine. Nat Rev Neurol 14: 457–469. doi:10.1038/s41582-018-0032-9
Gross B, Pawlak M, Lefebvre P, Staels B (2017) PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD. Nat Rev Endocrinol 13: 36–49. doi:10.1038/ nrendo.2016.135
Hennuyer N, Duplan I, Paquet C, Vanhoutte J, Woitrain E, Touche V, Colin S, Vallez E, Lestavel S, Lefebvre P, et al (2016) The novel selective PPARalpha modulator (SPPARMalpha) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis. Atherosclerosis 249: 200–208. doi:10.1016/j.atherosclerosis.2016.03.003
Ishibashi S, Arai H, Yokote K, Araki E, Suganami H, Yamashita S (2018) Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor alpha modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J Clin Lipidol 12: 173–184. doi:10.1016/j. jacl.2017.10.006
Jalouli M, Carlsson L, Ameen C, Linden D, Ljungberg A, Michalik L, Eden S, Wahli W, Oscarsson J (2003) Sex difference in hepatic peroxisome proliferator-activated receptor alpha expression: Influence of pituitary and gonadal hormones. Endocrinology 144: 101–109. doi:10.1210/en.2002-220630
Lalloyer F, Wouters K, Baron M, Caron S, Vallez E, Vanhoutte J, Bauge E, Shiri-Sverdlov R, Hofker M, Staels B, et al (2011) Peroxisome proliferator-activated receptor-alpha gene level differently affects lipid metabolism and inflammation in apolipoprotein E2 knock-in mice. Arterioscler Thromb Vasc Biol 31: 1573–1579. doi:10.1161/ atvbaha.110.220525
Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, Gonzalez FJ (1995) Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 15: 3012–3022. doi:10.1128/mcb.15.6.3012
Lefebvre P, Benomar Y, Staels B (2010) Retinoid X receptors: Common heterodimerization partners with distinct functions. Trends Endocrinol Metab 21: 676–683. doi:10.1016/j.tem.2010.06.009
Mariani MM, Malm T, Lamb R, Jay TR, Neilson L, Casali B, Medarametla L, Landreth GE (2017) Neuronally-directed effects of RXR activation in a mouse model of Alzheimer’s disease. Sci Rep 7: 42270. doi:10.1038/ srep42270
Middei S, Houeland G, Cavallucci V, Ammassari-Teule M, D’Amelio M, Marie H (2013) CREB is necessary for synaptic maintenance and learning-induced changes of the AMPA receptor GluA1 subunit. Hippocampus 23: 488–499. doi:10.1002/hipo.22108
Montagne A, Zhao Z, Zlokovic BV (2017) Alzheimer’s disease: A matter of blood-brain barrier dysfunction? J Exp Med 214: 3151–3169. doi:10.1084/jem.20171406
Mounier A, Georgiev D, Nam KN, Fitz NF, Castranio EL, Wolfe CM, Cronican AA, Schug J, Lefterov I, Koldamova R (2015) Bexarotene-activated retinoid X receptors regulate neuronal differentiation and dendritic complexity. J Neurosci 35: 11862–11876. doi:10.1523/jneurosci.1001-15.2015
Moutinho M, Landreth GE (2017) Therapeutic potential of nuclear receptor agonists in Alzheimer’s disease. J Lipid Res 58: 1937–1949. doi:10.1194/ jlr.r075556
Nam KN, Mounier A, Fitz NF, Wolfe C, Schug J, Lefterov I, Koldamova R (2016) RXR controlled regulatory networks identified in mouse brain counteract deleterious effects of Abeta oligomers. Sci Rep 6: 24048. doi:10.1038/srep24048
Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van EL, et al (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: Potential factors in amyloid plaque formation. J Neurosci 26: 10129–10140. doi:10.1523/ jneurosci.1202-06.2006
Paxinos G, Franklin KBJ (2001) The Mouse Brain in Stereotaxic Coordinates. San Diego, CA: Academic
Perez E, Bourguet W, Gronemeyer H, de Lera AR (2012) Modulation of RXR function through ligand design. Biochim Biophys Acta 1821: 57–69. doi:10.1016/j.bbalip.2011.04.003
Pickering M, Pickering BW, Murphy KJ, O’Connor JJ (2008) Discrimination of cell types in mixed cortical culture using calcium imaging: A comparison to immunocytochemical labeling. J Neurosci Methods 173: 27–33. doi:10.1016/j.jneumeth.2008.05.014
Pierrot N, Lhommel R, Quenon L, Hanseeuw B, Dricot L, Sindic C, Maloteaux JM, Octavea JN, Ivanoiu A (2016) Targretin improves cognitive and biological markers in a patient with Alzheimer’s disease. J Alzheimers Dis 49: 271–276. doi:10.3233/JAD-150405
Pierrot N, Tyteca D, D’auria L, Dewachter I, Gailly P, Hendrickx A, Tasiaux B, Haylani LE, Muls N, N’kuli F, et al (2013) Amyloid precursor protein controls cholesterol turnover needed for neuronal activity. EMBO Mol Med 5: 608–625. doi:10.1002/emmm.201202215
Raza-Iqbal S, Tanaka T, Anai M, Inagaki T, Matsumura Y, Ikeda K, Taguchi A, Gonzalez FJ, Sakai J, Kodama T (2015) Transcriptome analysis of K-877 (a novel selective PPARalpha modulator (SPPARMalpha))-regulated genes in primary human hepatocytes and the mouse liver. J Atheroscler Thromb 22: 754–772. doi:10.5551/jat.28720
Riecher-Rossler A (2017) Sex and gender differences in mental disorders. Lancet Psychiatry 4: 8–9. doi:10.1016/s2215-0366(16)30348-0
Roy A, Jana M, Corbett GT, Ramaswamy S, Kordower JH, Gonzalez FJ, Pahan K (2013) Regulation of cyclic AMP response element binding and hippocampal plasticity-related genes by peroxisome proliferator-activated receptor alpha. Cell Rep 4: 724–737. doi:10.1016/j. celrep.2013.07.028
Schmitt WB, Sprengel R, Mack V, Draft RW, Seeburg PH, Deacon RM, Rawlins JN, Bannerman DM (2005) Restoration of spatial working memory by genetic rescue of GluR-A-deficient mice. Nat Neurosci 8: 270–272. doi:10.1038/nn1412
Schulman IG, Shao G, Heyman RA (1998) Transactivation by retinoid X receptor-peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimers: Intermolecular synergy requires only the PPARgamma hormone-dependent activation function. Mol Cell Biol 18: 3483–3494. doi:10.1128/mcb.18.6.3483
Seibenhener ML, Wooten MW (2012) Isolation and culture of hippocampal neurons from prenatal mice. J Vis Exp 3634. doi:10.3791/3634
Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC (1998) Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 98: 2088–2093. doi:10.1161/01.cir.98.19.2088
Tata JR (1994) Autoregulation and crossregulation of nuclear receptor genes. Trends Endocrinol Metab 5: 283–290. doi:10.1016/1043-2760(94)p3203-j
Venkateswaran A, Laffitte BA, Joseph SB, Mak PA, Wilpitz DC, Edwards PA, Tontonoz P (2000) Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc Natl Acad Sci U S A 97: 12097–12102. doi:10.1073/pnas.200367697
Villers A, Ris L (2013) Improved preparation and preservation of hippocampal mouse slices for a very stable and reproducible recording of long-term potentiation. J Vis Exp doi:10.3791/50483
Warden A, Truitt J, Merriman M, Ponomareva O, Jameson K, Ferguson LB, Mayfield RD, Harris RA (2016) Localization of PPAR isotypes in the adult mouse and human brain. Sci Rep 6: 27618. doi:10.1038/srep27618
Watt MJ, Southgate RJ, Holmes AG, Febbraio MA (2004) Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor (PPAR) alpha and delta and PPAR coactivator 1alpha in human skeletal muscle, but not lipid regulatory genes. J Mol Endocrinol 33: 533–544. doi:10.1677/jme.1.01499
Yamazaki Y, Abe K, Toma T, Nishikawa M, Ozawa H, Okuda A, Araki T, Oda S, Inoue K, Shibuya K, et al (2007) Design and synthesis of highly potent and selective human peroxisome proliferator-activated receptor alpha agonists. Bioorg Med Chem Lett 17: 4689–4693. doi:10.1016/j. bmcl.2007.05.066
Zolezzi JM, Santos MJ, Bastias-Candia S, Pinto C, Godoy JA, Inestrosa NC (2017) PPARs in the central nervous system: Roles in neurodegeneration and neuroinflammation. Biol Rev Camb Philos Soc 92: 2046–2069. doi:10.1111/brv.12320