{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:54:55Z","timestamp":1778028895019,"version":"3.51.4"},"reference-count":113,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Health NIH","doi-asserted-by":"publisher","award":["R01 MH104131"],"award-info":[{"award-number":["R01 MH104131"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Health NIH","doi-asserted-by":"publisher","award":["MH105330"],"award-info":[{"award-number":["MH105330"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Health NIH","doi-asserted-by":"publisher","award":["MH087332"],"award-info":[{"award-number":["MH087332"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Health NIH","doi-asserted-by":"publisher","award":["DA052209"],"award-info":[{"award-number":["DA052209"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Health NIH","doi-asserted-by":"publisher","award":["P30 AG044271"],"award-info":[{"award-number":["P30 AG044271"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Health NIH","doi-asserted-by":"publisher","award":["P30 AG013319"],"award-info":[{"award-number":["P30 AG013319"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 MH104131"],"award-info":[{"award-number":["R01 MH104131"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH105330"],"award-info":[{"award-number":["MH105330"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH087332"],"award-info":[{"award-number":["MH087332"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA052209"],"award-info":[{"award-number":["DA052209"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AG044271"],"award-info":[{"award-number":["P30 AG044271"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AG013319"],"award-info":[{"award-number":["P30 AG013319"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Combination antiretroviral therapy (cART) has transformed HIV infection from a terminal disease to a manageable chronic health condition, extending patients\u2019 life expectancy to that of the general population. However, the incidence of HIV-associated neurocognitive disorders (HANDs) has persisted despite virological suppression. Patients with HIV display persistent signs of immune activation and inflammation despite cART. The arachidonic acid (AA) cascade is an important immune response system responsible for both pro- and anti-inflammatory processes. Methods: Lipidomics, mRNA and Western blotting analysis provide valuable insights into the molecular mechanisms surrounding arachidonic acid metabolism and the resulting inflammation caused by perturbations thereof. Results: Here, we report the presence of inflammatory eicosanoids in the brains of a transgenic mouse model of NeuroHIV that expresses soluble HIV-1 envelope glycoprotein in glial cells (HIVgp120tg mice). Additionally, we report that the effect of LTC4S knockout in HIVgp120tg mice resulted in the sexually dimorphic transcription of COX- and 5-LOX-related genes. Furthermore, the absence of LTC4S suppressed ERK1\/2 and p38 MAPK signaling activity in female mice only. The mass spectrometry-based lipidomic profiling of these mice reveals beneficial alterations to lipids in the brain. Conclusion: Targeting the AA cascade may hold potential in the treatment of neuroinflammation observed in NeuroHIV and HANDs.<\/jats:p>","DOI":"10.3390\/cells11132123","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T10:21:33Z","timestamp":1657016493000},"page":"2123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Arachidonic Acid Cascade and Eicosanoid Production Are Elevated While LTC4 Synthase Modulates the Lipidomics Profile in the Brain of the HIVgp120-Transgenic Mouse Model of NeuroHIV"],"prefix":"10.3390","volume":"11","author":[{"given":"Nina Y.","family":"Yuan","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California Riverside, 900 University Ave, Riverside, CA 92521, USA"},{"name":"Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricky","family":"Maung","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California Riverside, 900 University Ave, Riverside, CA 92521, USA"},{"name":"Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziying","family":"Xu","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-2413","authenticated-orcid":false,"given":"Xianlin","family":"Han","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA"},{"name":"Department of Medicine-Diabetes, University of Texas Health San Antonio, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3202-670X","authenticated-orcid":false,"given":"Marcus","family":"Kaul","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California Riverside, 900 University Ave, Riverside, CA 92521, USA"},{"name":"Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"ref_1","unstructured":"UN Joint Programme on HIV\/AIDS (UNAIDS) (2022, May 17). UNAIDS Data 2020. Available online: https:\/\/www.unaids.org\/en\/resources\/documents\/2020\/unaids-data."},{"key":"ref_2","unstructured":"Centers for Disease Control and Prevention (2022, May 17). HIV Surveillance Report, Available online: https:\/\/www.cdc.gov\/hiv\/library\/reports\/hiv-surveillance.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1080\/13550280290049615","article-title":"HIV-associated cognitive impairment before and after the advent of combination therapy","volume":"8","author":"Sacktor","year":"2002","journal-title":"J. Neurovirol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s13365-010-0006-1","article-title":"HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: Differences in rates, nature, and predictors","volume":"17","author":"Heaton","year":"2011","journal-title":"J. Neurovirol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/QAI.0000000000001992","article-title":"Effect of HIV Subtype and Antiretroviral Therapy on HIV-Associated Neurocognitive Disorder Stage in Rakai, Uganda","volume":"81","author":"Sacktor","year":"2019","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1212\/01.WNL.0000277520.94788.82","article-title":"Longitudinally preserved psychomotor performance in long-term asymptomatic HIV-infected individuals","volume":"69","author":"Cole","year":"2007","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/cid\/ciu862","article-title":"Neurocognitive change in the era of HIV combination antiretroviral therapy: The longitudinal CHARTER study","volume":"60","author":"Heaton","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1212\/WNL.0000000000002277","article-title":"Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study","volume":"86","author":"Sacktor","year":"2016","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1212\/WNL.0000000000003790","article-title":"Increased brain-predicted aging in treated HIV disease","volume":"88","author":"Cole","year":"2017","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s13365-012-0094-1","article-title":"Impact of HIV and aging on neuropsychological function","volume":"18","author":"Wendelken","year":"2012","journal-title":"J. Neurovirol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1097\/00002030-200401001-00012","article-title":"Cognitive impairment in older HIV-1-seropositive individuals: Prevalence and potential mechanisms","volume":"18","author":"Valcour","year":"2004","journal-title":"AIDS"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/00002030-200401001-00003","article-title":"Prevalence of cognitive disorders differs as a function of age in HIV virus infection","volume":"18","author":"Becker","year":"2004","journal-title":"AIDS"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1097\/00126334-200306012-00006","article-title":"Cognitive functioning in younger and older HIV-1-infected adults","volume":"33","author":"Wilkie","year":"2003","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1080\/13803395.2014.892061","article-title":"Verbal memory declines more rapidly with age in HIV infected versus uninfected adults","volume":"36","author":"Seider","year":"2014","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1007\/s10461-012-0229-7","article-title":"Lower cognitive reserve among individuals with syndromic HIV-associated neurocognitive disorders (HAND)","volume":"16","author":"Morgan","year":"2012","journal-title":"AIDS Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1080\/13803395.2010.499357","article-title":"Medication and finance management among HIV-infected adults: The impact of age and cognition","volume":"33","author":"Thames","year":"2011","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jana.2012.05.002","article-title":"The impact of neuropsychological performance on everyday functioning between older and younger adults with and without HIV","volume":"24","author":"Vance","year":"2013","journal-title":"J. Assoc. Nurses AIDS Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2217\/17460875.2.4.403","article-title":"Role of Lipids in Brain Injury and Diseases","volume":"2","author":"Adibhatla","year":"2007","journal-title":"Future Lipidol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yclnex.2018.05.001","article-title":"Lipids: An insight into the neurodegenerative disorders","volume":"20","author":"Ahsan","year":"2018","journal-title":"Clin. Nutr. Exp."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev.pathmechdis.3.121806.151409","article-title":"Anti-inflammatory and proresolving lipid mediators","volume":"3","author":"Serhan","year":"2008","journal-title":"Annu. Rev. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41392-020-00443-w","article-title":"Metabolism pathways of arachidonic acids: Mechanisms and potential therapeutic targets","volume":"6","author":"Wang","year":"2021","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/ana.410350513","article-title":"Elevated central nervous system prostaglandins in human immunodeficiency virus-associated dementia","volume":"35","author":"Griffin","year":"1994","journal-title":"Ann. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1742-4690-9-4","article-title":"Interactions between prostaglandins, leukotrienes and HIV-1: Possible implications for the central nervous system","volume":"9","author":"Bertin","year":"2012","journal-title":"Retrovirology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1084\/jem.176.6.1703","article-title":"Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: Implications for the neuropathogenesis of HIV disease","volume":"176","author":"Genis","year":"1992","journal-title":"J. Exp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1111\/j.1471-4159.2005.03267.x","article-title":"Human immunodeficiency virus type 1 envelope glycoprotein 120 induces cyclooxygenase-2 expression in neuroblastoma cells through a nuclear factor-kappaB and activating protein-1 mediated mechanism","volume":"94","author":"Alvarez","year":"2005","journal-title":"J. NeuroChem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1189\/jlb.68.3.423","article-title":"Induction of cyclooxygenase-2 expression during HIV-1-infected monocyte-derived macrophage and human brain microvascular endothelial cell interactions","volume":"68","author":"Pereira","year":"2000","journal-title":"J. Leukoc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0378-4274(02)00434-4","article-title":"Neurobiological mediators of neuronal apoptosis in experimental neuroAIDS","volume":"139","author":"Corasaniti","year":"2003","journal-title":"Toxicol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1006\/bbrc.1998.8321","article-title":"HIV-1 gp120-induced apoptosis in the rat neocortex involves enhanced expression of cyclo-oxygenase type 2 (COX-2)","volume":"244","author":"Bagetta","year":"1998","journal-title":"BioChem. Biophys. Res. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1046\/j.1471-4159.2000.0750196.x","article-title":"HIV-1 coat glycoprotein gp120 induces apoptosis in rat brain neocortex by deranging the arachidonate cascade in favor of prostanoids","volume":"75","author":"Maccarrone","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s13365-011-0026-5","article-title":"Human immunodeficiency virus type 1 clade B and C gp120 differentially induce neurotoxin arachidonic acid in human astrocytes: Implications for neuroAIDS","volume":"17","author":"Samikkannu","year":"2011","journal-title":"J. Neurovirol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1073\/pnas.86.2.621","article-title":"Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1","volume":"86","author":"Wahl","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/jcbfm.2010.111","article-title":"Imaging upregulated brain arachidonic acid metabolism in HIV-1 transgenic rats","volume":"31","author":"Basselin","year":"2011","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/1742-2094-8-101","article-title":"Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats","volume":"8","author":"Rao","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1111\/j.1460-9568.1995.tb01048.x","article-title":"The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid","volume":"7","author":"Dreyer","year":"1995","journal-title":"Eur. J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0165-5728(92)90100-Y","article-title":"Mediator release in cerebrospinal fluid of human immunodeficiency virus-positive patients with central nervous system involvement","volume":"38","author":"Froldi","year":"1992","journal-title":"J. Neuroimmunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cassol, E., Misra, V., Holman, A., Kamat, A., Morgello, S., and Gabuzda, D. (2013). Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-203"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jneuroim.2004.09.007","article-title":"Microarray analysis of activated mixed glial (microglia) and monocyte-derived macrophage gene expression","volume":"157","author":"Albright","year":"2004","journal-title":"J. Neuroimmunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.4049\/jimmunol.1302915","article-title":"CCR5 knockout prevents neuronal injury and behavioral impairment induced in a transgenic mouse model by a CXCR4-using HIV-1 glycoprotein 120","volume":"193","author":"Maung","year":"2014","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/367188a0","article-title":"Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice","volume":"367","author":"Toggas","year":"1994","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1006\/viro.1999.0136","article-title":"CXCR4 mediates entry and productive infection of syncytia-inducing (X4) HIV-1 strains in primary macrophages","volume":"269","author":"Valentin","year":"2000","journal-title":"Virology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s13365-017-0584-2","article-title":"Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research","volume":"24","author":"Thaney","year":"2018","journal-title":"J. Neurovirol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"22608","DOI":"10.1074\/jbc.M103562200","article-title":"Attenuated zymosan-induced peritoneal vascular permeability and IgE-dependent passive cutaneous anaphylaxis in mice lacking leukotriene C4 synthase","volume":"276","author":"Kanaoka","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_43","unstructured":"Kennedy, P., Dorow, S., Bickel, J., Domanski, P., Pisano, M., and Soulika, A. (2022, May 17). Immunoaffinity Mass Spectrometry for Leukotriene Analysis in Brain. Cayman Chemical. Available online: https:\/\/cdn2.caymanchem.com\/cdn\/cms\/caymanchem\/LiteratureCMS\/800164.pdf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/s12974-020-01894-2","article-title":"A pivotal role for Interferon-alpha receptor-1 in neuronal injury induced by HIV-1","volume":"17","author":"Singh","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.bbi.2020.06.016","article-title":"Lipocalin-2 mediates HIV-1 induced neuronal injury and behavioral deficits by overriding CCR5-dependent protection","volume":"89","author":"Shah","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40478-017-0460-6","article-title":"Oligomeric amyloid-beta induces MAPK-mediated activation of brain cytosolic and calcium-independent phospholipase A2 in a spatial-specific manner","volume":"5","author":"Palavicini","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1111\/j.1471-4159.2006.03794.x","article-title":"Abundance of triacylglycerols in ganglia and their depletion in diabetic mice: Implications for the role of altered triacylglycerols in diabetic neuropathy","volume":"97","author":"Cheng","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1471-4159.2006.04342.x","article-title":"Alterations in lipid homeostasis of mouse dorsal root ganglia induced by apolipoprotein E deficiency: A shotgun lipidomics study","volume":"101","author":"Cheng","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1002\/rcm.3595","article-title":"Microfluidics-based electrospray ionization enhances the intrasource separation of lipid classes and extends identification of individual molecular species through multi-dimensional mass spectrometry: Development of an automated high-throughput platform for shotgun lipidomics","volume":"22","author":"Han","year":"2008","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4356","DOI":"10.1021\/ac900241u","article-title":"Automated lipid identification and quantification by multidimensional mass spectrometry-based shotgun lipidomics","volume":"81","author":"Yang","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8212","DOI":"10.1073\/pnas.96.14.8212","article-title":"Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis","volume":"96","author":"Kaul","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/sj.cdd.4402006","article-title":"HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection","volume":"14","author":"Kaul","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.4049\/jimmunol.0902535","article-title":"Activation of p38 MAPK is required in monocytic and neuronal cells for HIV glycoprotein 120-induced neurotoxicity","volume":"185","author":"Medders","year":"2010","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nrneurol.2016.53","article-title":"HIV-associated neurocognitive disorder\u2014Pathogenesis and prospects for treatment","volume":"12","author":"Saylor","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12746","DOI":"10.1073\/pnas.1404372111","article-title":"Phospholipase A2 regulates eicosanoid class switching during inflammasome activation","volume":"111","author":"Norris","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S1471-4906(01)02154-8","article-title":"Prostaglandins as modulators of immunity","volume":"23","author":"Harris","year":"2002","journal-title":"Trends Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.molmed.2008.08.005","article-title":"Arachidonic-acid-derived eicosanoids: Roles in biology and immunopathology","volume":"14","author":"Harizi","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nri3859","article-title":"Eicosanoid storm in infection and inflammation","volume":"15","author":"Dennis","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.tips.2012.02.004","article-title":"Prostaglandins and chronic inflammation","volume":"33","author":"Aoki","year":"2012","journal-title":"Trends Pharm. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fimmu.2018.00038","article-title":"Bioactive Lipids and Chronic Inflammation: Managing the Fire within","volume":"9","author":"Chiurchiu","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0197-4580(00)00124-X","article-title":"Inflammation and Alzheimer\u2019s disease","volume":"21","author":"Akiyama","year":"2000","journal-title":"Neurobiol. Aging"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s11481-011-9312-5","article-title":"Non-steroidal anti-inflammatory drugs and cognitive function: Are prostaglandins at the heart of cognitive impairment in dementia and delirium?","volume":"7","author":"Cunningham","year":"2012","journal-title":"J. Neuroimmune Pharm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1039\/c2mb05503a","article-title":"Dynamic eicosanoid responses upon different inhibitor and combination treatments on the arachidonic acid metabolic network","volume":"8","author":"He","year":"2012","journal-title":"Mol. Biosyst."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s11888-012-0146-1","article-title":"Lipoxygenase and Cyclooxygenase Pathways and Colorectal Cancer Prevention","volume":"8","author":"Rao","year":"2012","journal-title":"Curr. Colorectal Cancer Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.ejps.2018.06.003","article-title":"Safer anti-inflammatory therapy through dual COX-2\/5-LOX inhibitors: A structure-based approach","volume":"121","author":"Manju","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"781889","DOI":"10.3389\/fphar.2022.781889","article-title":"Lipoxins in the Nervous System: Brighter Prospects for Neuroprotection","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.2353\/ajpath.2010.100322","article-title":"Novel lipid mediators and resolution mechanisms in acute inflammation: To resolve or not?","volume":"177","author":"Serhan","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature13324","article-title":"Mfsd2a is critical for the formation and function of the blood-brain barrier","volume":"509","author":"Lacoste","year":"2014","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nature13241","article-title":"Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid","volume":"509","author":"Nguyen","year":"2014","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Chan, J.P., Wong, B.H., Chiin, C.F., Galam, D.L.A., Foo, J.C., Wong, L.C., Ghosh, S., Wenk, M.R., Cazenave-Gassiot, A., and Silver, D.L. (2018). The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2006443"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Farooqui, A.A. (2009). Beneficial Effects of Fish Oil on Human Brain, Springer.","DOI":"10.1007\/978-1-4419-0543-7"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1093\/intimm\/dxz001","article-title":"Omega-3 fatty acid-derived mediators that control inflammation and tissue homeostasis","volume":"31","author":"Ishihara","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1750-3639.2005.tb00513.x","article-title":"Neuroprotectin D1 (NPD1): A DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress","volume":"15","author":"Bazan","year":"2005","journal-title":"Brain Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3267172","DOI":"10.1155\/2020\/3267172","article-title":"Resolution of Inflammation in Neurodegenerative Diseases: The Role of Resolvins","volume":"2020","author":"Chamani","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0092-8674(93)90666-E","article-title":"cPLA2 is phosphorylated and activated by MAP kinase","volume":"72","author":"Lin","year":"1993","journal-title":"Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"20146","DOI":"10.1074\/jbc.M908941199","article-title":"Cytosolic phospholipase A2 is required for macrophage arachidonic acid release by agonists that Do and Do not mobilize calcium. Novel role of mitogen-activated protein kinase pathways in cytosolic phospholipase A2 regulation","volume":"275","author":"Gijon","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Han, X. (2016). Lipidomics: Comprehensive Mass Spectrometry of Lipids, Wiley. (online resource).","DOI":"10.1002\/9781119085263"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s007020070051","article-title":"Membrane breakdown in acute and chronic neurodegeneration: Focus on choline-containing phospholipids","volume":"107","author":"Klein","year":"2000","journal-title":"J. Neural. Transm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1073\/pnas.89.5.1671","article-title":"Evidence for a membrane defect in Alzheimer disease brain","volume":"89","author":"Nitsch","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"14509","DOI":"10.1038\/s41598-020-71510-z","article-title":"Untargeted lipidomics reveals progression of early Alzheimer\u2019s disease in APP\/PS1 transgenic mice","volume":"10","author":"Zhang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fncel.2019.00002","article-title":"Phosphatidic Acid: From Pleiotropic Functions to Neuronal Pathology","volume":"13","author":"Tanguy","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jbior.2016.09.004","article-title":"Phosphatidic acid and neurotransmission","volume":"63","author":"Raben","year":"2017","journal-title":"Adv. Biol. Regul."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1046\/j.1471-4159.2002.00997.x","article-title":"Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer\u2019s disease: Potential role in disease pathogenesis","volume":"82","author":"Han","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Hsiao, J.H., Fu, Y., Hill, A.F., Halliday, G.M., and Kim, W.S. (2013). Elevation in sphingomyelin synthase activity is associated with increases in amyloid-beta peptide generation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074016"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.neurobiolaging.2008.05.010","article-title":"Deregulation of sphingolipid metabolism in Alzheimer\u2019s disease","volume":"31","author":"He","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3389\/fneur.2020.00437","article-title":"Exploring Sphingolipid Implications in Neurodegeneration","volume":"11","author":"Alessenko","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.4103\/1673-5374.308087","article-title":"Nuclear sphingomyelin in neurodegenerative diseases","volume":"16","author":"Albi","year":"2021","journal-title":"Neural. Regen. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/j.addr.2003.07.007","article-title":"Aberrant sphingomyelin\/ceramide metabolic-induced neuronal endosomal\/lysosomal dysfunction: Potential pathological consequences in age-related neurodegeneration","volume":"55","author":"Soreghan","year":"2003","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"488","DOI":"10.3389\/fnins.2016.00488","article-title":"From Molecules to the Clinic: Linking Schizophrenia and Metabolic Syndrome through Sphingolipids Metabolism","volume":"10","author":"Castillo","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1007\/s11481-013-9506-0","article-title":"A biological perspective of CSF lipids as surrogate markers for cognitive status in HIV","volume":"8","author":"Haughey","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/jnc.15044","article-title":"Role of sphingolipid metabolism in neurodegeneration","volume":"158","author":"Alaamery","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ana.10828","article-title":"Perturbation of sphingolipid metabolism and ceramide production in HIV-dementia","volume":"55","author":"Haughey","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/BF03210850","article-title":"Disturbance in cerebral spinal fluid sphingolipid content is associated with memory impairment in subjects infected with the human immunodeficiency virus","volume":"16","author":"Mielke","year":"2010","journal-title":"J. Neurovirol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1212\/WNL.0b013e3182a9565e","article-title":"A lipid storage-like disorder contributes to cognitive decline in HIV-infected subjects","volume":"81","author":"Bandaru","year":"2013","journal-title":"Neurology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1212\/01.wnl.0000260610.79853.47","article-title":"Associative and predictive biomarkers of dementia in HIV-1-infected patients","volume":"68","author":"Bandaru","year":"2007","journal-title":"Neurology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0163-7827(00)00017-5","article-title":"The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina","volume":"40","author":"Lauritzen","year":"2001","journal-title":"Prog. Lipid Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.3945\/an.116.012963","article-title":"Docosahexaenoic Acid","volume":"7","author":"Richard","year":"2016","journal-title":"Adv. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0005-2760(94)90077-9","article-title":"Lysophosphatidylcholine from white muscle of bonito Euthynnus pelamis (Linnaeus): Involvement of phospholipase A1 activity for its production","volume":"1214","author":"Satouchi","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/BF02536613","article-title":"Composition of phospholipids of white muscle of six tuna species","volume":"30","author":"Medina","year":"1995","journal-title":"Lipids"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1007\/s00216-015-8671-9","article-title":"Identification of isobaric lyso-phosphatidylcholines in lipid extracts of gilthead sea bream (Sparus aurata) fillets by hydrophilic interaction liquid chromatography coupled to high-resolution Fourier-transform mass spectrometry","volume":"407","author":"Granafei","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1093\/advances\/nmaa024","article-title":"Perspective: The Potential Role of Circulating Lysophosphatidylcholine in Neuroprotection against Alzheimer Disease","volume":"11","author":"Semba","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.addr.2020.01.004","article-title":"Fatty acid metabolism in the progression and resolution of CNS disorders","volume":"159","author":"Bogie","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/cns.12596","article-title":"Cysteinyl Leukotrienes and Their Receptors: Emerging Therapeutic Targets in Central Nervous System Disorders","volume":"22","author":"Ghosh","year":"2016","journal-title":"CNS Neurosci. Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1136\/ard.62.6.501","article-title":"Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective non-steroidal anti-inflammatory drugs","volume":"62","author":"Lajeunesse","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Yang, K., Ma, W., Liang, H., Ouyang, Q., Tang, C., and Lai, L. (2007). Dynamic simulations on the arachidonic acid metabolic network. PLoS Comput. Biol., 3.","DOI":"10.1371\/journal.pcbi.0030055"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2017.06.128","article-title":"Sex-biased eicosanoid biology: Impact for sex differences in inflammation and consequences for pharmacotherapy","volume":"145","author":"Pace","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.phrs.2018.11.024","article-title":"Leukotriene-mediated sex dimorphism in murine asthma-like features during allergen sensitization","volume":"139","author":"Rossi","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1038\/s41598-017-03696-8","article-title":"Sex differences in prostaglandin biosynthesis in neutrophils during acute inflammation","volume":"7","author":"Pace","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"581346","DOI":"10.3389\/fneur.2020.581346","article-title":"The Prevalence of Frascati-Criteria-Based HIV-Associated Neurocognitive Disorder (HAND) in HIV-Infected Adults: A Systematic Review and Meta-Analysis","volume":"11","author":"Wei","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/QAI.0000000000001764","article-title":"Differences in Cognitive Function Between Women and Men With HIV","volume":"79","author":"Maki","year":"2018","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s11065-009-9093-2","article-title":"HIV, cognition and women","volume":"19","author":"Maki","year":"2009","journal-title":"Neuropsychol. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/j.1440-1819.2008.01841.x","article-title":"Neuropsychological impairment and gender differences in HIV-1 infection","volume":"62","author":"Alvarez","year":"2008","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/QAI.0000000000002029","article-title":"Elevated Depressive Symptoms Are a Stronger Predictor of Executive Dysfunction in HIV-Infected Women Than in Men","volume":"81","author":"Rubin","year":"2019","journal-title":"J. Acquir. Immune Defic. Syndr."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/13\/2123\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:43:11Z","timestamp":1760139791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/13\/2123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,5]]},"references-count":113,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["cells11132123"],"URL":"https:\/\/doi.org\/10.3390\/cells11132123","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,5]]}}}