{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T05:01:51Z","timestamp":1773982911145,"version":"3.50.1"},"reference-count":99,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R03DA044087"],"award-info":[{"award-number":["R03DA044087"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>HIV-1 and drug abuse have been indissolubly allied as entwined epidemics. It is well-known that drug abuse can hasten the progression of HIV-1 and its consequences, especially in the brain, causing neuroinflammation. This study reports the combined effects of HIV-1 Transactivator of Transcription (Tat) protein and cocaine on miR-124 promoter DNA methylation and its role in microglial activation and neuroinflammation. The exposure of mouse primary microglial cells to HIV-1 Tat (25 ng\/mL) and\/or cocaine (10 \u03bcM) resulted in the significantly decreased expression of primary (pri)-miR-124-1, pri-miR-124-2, and mature miR-124 with a concomitant upregulation in DNMT1 expression as well as global DNA methylation. Our bisulfite-converted genomic DNA sequencing also revealed significant promoter DNA methylation in the pri-miR-124-1 and pri-miR-124-2 in HIV-1 Tat- and cocaine-exposed mouse primary microglial cells. We also found the increased expression of proinflammatory cytokines such as IL1\u03b2, IL6 and TNF in the mouse primary microglia exposed to HIV-1 Tat and cocaine correlated with microglial activation. Overall, our findings demonstrate that the exposure of mouse primary microglia to both HIV-1 Tat and cocaine could result in intensified microglial activation via the promoter DNA hypermethylation of miR-124, leading to the exacerbated release of proinflammatory cytokines, ultimately culminating in neuroinflammation.<\/jats:p>","DOI":"10.3390\/ijms232315017","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T04:32:53Z","timestamp":1669782773000},"page":"15017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Epigenetic Role of miR-124 in HIV-1 Tat- and Cocaine-Mediated Microglial Activation"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0386-5611","authenticated-orcid":false,"given":"Palsamy","family":"Periyasamy","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7125-2289","authenticated-orcid":false,"given":"Annadurai","family":"Thangaraj","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muthukumar","family":"Kannan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2225-1129","authenticated-orcid":false,"given":"Abiola","family":"Oladapo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilpa","family":"Buch","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1742-6405-11-13","article-title":"Viral and cellular factors underlying neuropathogenesis in HIV associated neurocognitive disorders (HAND)","volume":"11","author":"Rao","year":"2014","journal-title":"AIDS Res. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2014.10.008","article-title":"Role of the immune system in HIV-associated neuroinflammation and neurocognitive implications","volume":"45","author":"Hong","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"146426","DOI":"10.1016\/j.brainres.2019.146426","article-title":"The impact of substance abuse on HIV-mediated neuropathogenesis in the current ART era","volume":"1724","author":"Chilunda","year":"2019","journal-title":"Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1097\/WCO.0000000000000807","article-title":"Chronic inflammation mediates brain injury in HIV infection: Relevance for cure strategies","volume":"33","author":"McArthur","year":"2020","journal-title":"Curr. Opin. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fcimb.2020.00061","article-title":"HIV-1 Tat: Role in Bystander Toxicity","volume":"10","author":"Ajasin","year":"2020","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1046\/j.1471-4159.2003.01543.x","article-title":"HIV-Tat protein induces oxidative and inflammatory pathways in brain endothelium","volume":"84","author":"Toborek","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/320367a0","article-title":"The trans-activator gene of HTLV-III is essential for virus replication","volume":"320","author":"Fisher","year":"1986","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17852","DOI":"10.1074\/jbc.273.28.17852","article-title":"HIV-1 Tat induces neuronal death via tumor necrosis factor-alpha and activation of non-N-methyl-D-aspartate receptors by a NFkappaB-independent mechanism","volume":"273","author":"New","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.brainresrev.2005.04.002","article-title":"HIV-dementia, Tat-induced oxidative stress, and antioxidant therapeutic considerations","volume":"50","author":"Pocernich","year":"2005","journal-title":"Brain Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.brainres.2005.03.031","article-title":"HIV-1 viral proteins gp120 and Tat induce oxidative stress in brain endothelial cells","volume":"1045","author":"Price","year":"2005","journal-title":"Brain Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3109\/13550289809114529","article-title":"Neuronal apoptosis induced by HIV-1 Tat protein and TNF-alpha: Potentiation of neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia","volume":"4","author":"Shi","year":"1998","journal-title":"J. Neurovirol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s11481-018-9788-3","article-title":"Critical Role of Beclin1 in HIV Tat and Morphine-Induced Inflammation and Calcium Release in Glial Cells from Autophagy Deficient Mouse","volume":"13","author":"Lapierre","year":"2018","journal-title":"J. Neuroimmune Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1080\/15548627.2018.1476810","article-title":"HIV-1 TAT-mediated microglial activation: Role of mitochondrial dysfunction and defective mitophagy","volume":"14","author":"Thangaraj","year":"2018","journal-title":"Autophagy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/cbf.3357","article-title":"HIV-1 Tat-induced bystander apoptosis in Jurkat cells involves unfolded protein responses","volume":"36","author":"Campestrini","year":"2018","journal-title":"Cell Biochem. Funct."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22819","DOI":"10.1074\/jbc.M116.731828","article-title":"HIV-1 Tat Induces Unfolded Protein Response and Endoplasmic Reticulum Stress in Astrocytes and Causes Neurotoxicity through Glial Fibrillary Acidic Protein (GFAP) Activation and Aggregation","volume":"291","author":"Fan","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11362","DOI":"10.1523\/JNEUROSCI.1208-16.2016","article-title":"HIV Tat Impairs Neurogenesis through Functioning As a Notch Ligand and Activation of Notch Signaling Pathway","volume":"36","author":"Fan","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrneurol.2016.27","article-title":"HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment","volume":"12","author":"Saylor","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.bbi.2019.03.011","article-title":"HIV-1 Tat-mediated microglial inflammation involves a novel miRNA-34a-NLRC5-NFkappaB signaling axis","volume":"80","author":"Periyasamy","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1523\/JNEUROSCI.3045-16.2017","article-title":"HIV-1 Tat Primes and Activates Microglial NLRP3 Inflammasome-Mediated Neuroinflammation","volume":"37","author":"Chivero","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101843","DOI":"10.1016\/j.redox.2020.101843","article-title":"HIV TAT-mediated microglial senescence: Role of SIRT3-dependent mitochondrial oxidative stress","volume":"40","author":"Thangaraj","year":"2021","journal-title":"Redox Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1007\/s11481-019-09869-8","article-title":"HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture","volume":"15","author":"Hu","year":"2020","journal-title":"J. Neuroimmune Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/s12974-016-0716-2","article-title":"HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression","volume":"13","author":"Rahimian","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"41125","DOI":"10.1074\/jbc.M111.268466","article-title":"HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs","volume":"286","author":"Chang","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5367","DOI":"10.1523\/JNEUROSCI.3474-17.2018","article-title":"Epigenetic Promoter DNA Methylation of miR-124 Promotes HIV-1 Tat-Mediated Microglial Activation via MECP2-STAT3 Axis","volume":"38","author":"Periyasamy","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s11481-018-9779-4","article-title":"Exosomal miR-9 Released from HIV Tat Stimulated Astrocytes Mediates Microglial Migration","volume":"13","author":"Yang","year":"2018","journal-title":"J. Neuroimmune Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11812","DOI":"10.1523\/JNEUROSCI.1139-14.2014","article-title":"Tat 101-mediated enhancement of brain pericyte migration involves platelet-derived growth factor subunit B homodimer: Implications for human immunodeficiency virus-associated neurocognitive disorders","volume":"34","author":"Niu","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134951","DOI":"10.1016\/j.neulet.2020.134951","article-title":"Cocaine self-administration differentially activates microglia in the mouse brain","volume":"728","author":"Burkovetskaya","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1080\/15548627.2019.1607686","article-title":"Mitigation of cocaine-mediated mitochondrial damage, defective mitophagy and microglial activation by superoxide dismutase mimetics","volume":"16","author":"Thangaraj","year":"2020","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.nbd.2018.05.017","article-title":"Cocaine-mediated activation of microglia and microglial MeCP2 and BDNF production","volume":"117","author":"Cotto","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1007\/s12035-017-0584-5","article-title":"Cocaine-Mediated Downregulation of miR-124 Activates Microglia by Targeting KLF4 and TLR4 Signaling","volume":"55","author":"Periyasamy","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1080\/15592294.2016.1232233","article-title":"Cocaine-mediated downregulation of microglial miR-124 expression involves promoter DNA methylation","volume":"11","author":"Guo","year":"2016","journal-title":"Epigenetics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1080\/15548627.2015.1052205","article-title":"Cocaine-mediated microglial activation involves the ER stress-autophagy axis","volume":"11","author":"Guo","year":"2015","journal-title":"Autophagy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12974-016-0501-2","article-title":"Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis","volume":"13","author":"Liao","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.biopsych.2020.08.012","article-title":"Cocaine Triggers Astrocyte-Mediated Synaptogenesis","volume":"89","author":"Wang","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sivalingam, K., and Samikkannu, T. (2020). Neuroprotective Effect of Piracetam against Cocaine-Induced Neuro Epigenetic Modification of DNA Methylation in Astrocytes. Brain Sci., 10.","DOI":"10.3390\/brainsci10090611"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1080\/15548627.2016.1183844","article-title":"Cocaine induces astrocytosis through ER stress-mediated activation of autophagy","volume":"12","author":"Periyasamy","year":"2016","journal-title":"Autophagy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1007\/s12035-020-02184-x","article-title":"NLRP3 Inflammasome Blockade Reduces Cocaine-Induced Microglial Activation and Neuroinflammation","volume":"58","author":"Chivero","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"27864","DOI":"10.1038\/srep27864","article-title":"Effect of Cocaine on HIV Infection and Inflammasome Gene Expression Profile in HIV Infected Macrophages","volume":"6","author":"Atluri","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1083\/jcb.201712011","article-title":"Cocaine-induced release of CXCL10 from pericytes regulates monocyte transmigration into the CNS","volume":"218","author":"Niu","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1007\/s12035-018-1325-0","article-title":"Cocaine Mediated Neuroinflammation: Role of Dysregulated Autophagy in Pericytes","volume":"56","author":"Sil","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.biopsych.2017.09.016","article-title":"Cocaine Rearranges the Neuronal Epigenome","volume":"82","author":"Schmidt","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41419-018-0422-3","article-title":"Astrocytic metabolic switch is a novel etiology for Cocaine and HIV-1 Tat-mediated neurotoxicity","volume":"9","author":"Natarajaseenivasan","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1002\/glia.23291","article-title":"Cocaine and HIV-1 Tat disrupt cholesterol homeostasis in astrocytes: Implications for HIV-associated neurocognitive disorders in cocaine user patients","volume":"66","author":"Cotto","year":"2018","journal-title":"Glia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9299","DOI":"10.1002\/jcp.26322","article-title":"Network analysis of hippocampal neurons by microelectrode array in the presence of HIV-1 Tat and cocaine","volume":"233","author":"Shekarabi","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1007\/s12035-020-02131-w","article-title":"HIV-Tat and Cocaine Impact Brain Energy Metabolism: Redox Modification and Mitochondrial Biogenesis Influence NRF Transcription-Mediated Neurodegeneration","volume":"58","author":"Sivalingam","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s11481-019-09885-8","article-title":"Inhibition of the Dead Box RNA Helicase 3 Prevents HIV-1 Tat and Cocaine-Induced Neurotoxicity by Targeting Microglia Activation","volume":"15","author":"Aksenova","year":"2020","journal-title":"J. Neuroimmune Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s11481-016-9669-6","article-title":"HIV-1 Tat and Cocaine Impair Survival of Cultured Primary Neuronal Cells via a Mitochondrial Pathway","volume":"11","author":"Darbinian","year":"2016","journal-title":"J. Neuroimmune Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"894","DOI":"10.3389\/fmicb.2015.00894","article-title":"HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol","volume":"6","author":"Bertrand","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/QAI.0b013e3181900129","article-title":"Crack-cocaine use accelerates HIV disease progression in a cohort of HIV-positive drug users","volume":"50","author":"Baum","year":"2009","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1212\/WNL.0000000000002485","article-title":"Neuroinflammation in treated HIV-positive individuals: A TSPO PET study","volume":"86","author":"Vera","year":"2016","journal-title":"Neurology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1097\/QAD.0000000000001858","article-title":"Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy","volume":"32","author":"Rubin","year":"2018","journal-title":"AIDS"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"a007120","DOI":"10.1101\/cshperspect.a007120","article-title":"HIV-1-related central nervous system disease: Current issues in pathogenesis, diagnosis, and treatment","volume":"2","author":"Spudich","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/npp.2016.121","article-title":"Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse","volume":"42","author":"Lacagnina","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/s41380-020-0651-6","article-title":"Hippocampal neural stem cells and microglia response to experimental inflammatory bowel disease (IBD)","volume":"26","author":"Gampierakis","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Desplats, P., Dumaop, W., Cronin, P., Gianella, S., Woods, S., Letendre, S., Smith, D., Masliah, E., and Grant, I. (2014). Epigenetic alterations in the brain associated with HIV-1 infection and methamphetamine dependence. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102555"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nm.2266","article-title":"MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C\/EBP-alpha-PU.1 pathway","volume":"17","author":"Ponomarev","year":"2011","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/dneu.22328","article-title":"miR-124 Contributes to the functional maturity of microglia","volume":"76","author":"Svahn","year":"2016","journal-title":"Dev. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fncel.2015.00193","article-title":"An updated role of microRNA-124 in central nervous system disorders: A review","volume":"9","author":"Sun","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11466","DOI":"10.1073\/pnas.97.21.11466","article-title":"Selective CXCR4 antagonism by Tat: Implications for in vivo expansion of coreceptor use by HIV-1","volume":"97","author":"Xiao","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/375497a0","article-title":"Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120","volume":"375","author":"Westendorp","year":"1995","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1038\/nm0996-960","article-title":"HIV-1 Tat protein as a potential AIDS vaccine","volume":"2","author":"Goldstein","year":"1996","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"685","DOI":"10.3109\/13550289909021297","article-title":"Role of HIV-1 Tat and CC chemokine MIP-1alpha in the pathogenesis of HIV associated central nervous system disorders","volume":"5","author":"Bonwetsch","year":"1999","journal-title":"J. Neurovirol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17098","DOI":"10.1074\/jbc.274.24.17098","article-title":"Transient exposure to HIV-1 Tat protein results in cytokine production in macrophages and astrocytes. A hit and run phenomenon","volume":"274","author":"Nath","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1038\/sj.jcbfm.9600254","article-title":"HIV-TAT protein upregulates expression of multidrug resistance protein 1 in the blood-brain barrier","volume":"26","author":"Hayashi","year":"2006","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1126\/science.56036","article-title":"Cocaine: Plasma concentrations after intranasal application in man","volume":"191","author":"Barash","year":"1976","journal-title":"Science"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.paf.0000118960.58334.a9","article-title":"Criteria for the interpretation of cocaine levels in human biological samples and their relation to the cause of death","volume":"25","author":"Stephens","year":"2004","journal-title":"Am. J. Forensic. Med. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1520\/JFS14828J","article-title":"Regional distribution of cocaine in postmortem brain of chronic human cocaine users","volume":"45","author":"Kalasinsky","year":"2000","journal-title":"J. Forensic. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/07853890.2020.1814962","article-title":"Important role of microglia in HIV-1 associated neurocognitive disorders and the molecular pathways implicated in its pathogenesis","volume":"53","author":"Borrajo","year":"2021","journal-title":"Ann. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1097\/00002030-199607000-00007","article-title":"Expression of HIV regulatory and structural mRNA in the central nervous system","volume":"10","author":"Wiley","year":"1996","journal-title":"AIDS"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3109\/13550280009013158","article-title":"Detection of the human immunodeficiency virus regulatory protein tat in CNS tissues","volume":"6","author":"Hudson","year":"2000","journal-title":"J. Neurovirol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s12967-016-0893-x","article-title":"Regulatory mechanisms of microRNA expression","volume":"14","author":"Gulyaeva","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1750-9378-9-41","article-title":"HIV-1 Tat induces DNMT over-expression through microRNA dysregulation in HIV-related non Hodgkin lymphomas","volume":"9","author":"Luzzi","year":"2014","journal-title":"Infect. Agent Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"149","DOI":"10.4161\/epi.3.3.6372","article-title":"The early expressed HIV-1 genes regulate DNMT1 expression","volume":"3","author":"Youngblood","year":"2008","journal-title":"Epigenetics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9753","DOI":"10.1128\/JVI.75.20.9753-9761.2001","article-title":"Infection of lymphoid cells by integration-defective human immunodeficiency virus type 1 increases de novo methylation","volume":"75","author":"Fang","year":"2001","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/1476-4598-9-167","article-title":"Methylation-mediated silencing and tumour suppressive function of hsa-miR-124 in cervical cancer","volume":"9","author":"Wilting","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1053\/j.gastro.2013.07.001","article-title":"MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis","volume":"145","author":"Koukos","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"524204","DOI":"10.1155\/2013\/524204","article-title":"Research of the methylation status of miR-124a gene promoter among rheumatoid arthritis patients","volume":"2013","author":"Zhou","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Chu, M., Chang, Y., Guo, Y., Wang, N., Cui, J., and Gao, W.Q. (2015). Regulation and methylation of tumor suppressor miR-124 by androgen receptor in prostate cancer cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116197"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.1038\/onc.2016.91","article-title":"Epigenetic silencing of miR-124 prevents spermine oxidase regulation: Implications for Helicobacter pylori-induced gastric cancer","volume":"35","author":"Sierra","year":"2016","journal-title":"Oncogene"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"26027","DOI":"10.18632\/oncotarget.8266","article-title":"Methylation-regulated miR-124-1 suppresses tumorigenesis in hepatocellular carcinoma by targeting CASC3","volume":"7","author":"Xu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"104515","DOI":"10.1016\/j.phrs.2019.104515","article-title":"miR-124 and Parkinson\u2019s disease: A biomarker with therapeutic potential","volume":"150","author":"Angelopoulou","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Liu, X., Feng, Z., Du, L., Huang, Y., Ge, J., Deng, Y., and Mei, Z. (2019). The Potential Role of MicroRNA-124 in Cerebral Ischemia Injury. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010120"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Slota, J.A., and Booth, S.A. (2019). MicroRNAs in Neuroinflammation: Implications in Disease Pathogenesis, Biomarker Discovery and Therapeutic Applications. Noncoding RNA, 5.","DOI":"10.3390\/ncrna5020035"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1177\/1073858417721150","article-title":"MicroRNAs: Roles in Regulating Neuroinflammation","volume":"24","author":"Gaudet","year":"2018","journal-title":"Neuroscientist"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12943-016-0575-6","article-title":"Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2","volume":"16","author":"Niu","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.toxlet.2011.11.032","article-title":"The miR-124 regulates the expression of BACE1\/beta-secretase correlated with cell death in Alzheimer\u2019s disease","volume":"209","author":"Fang","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.toxlet.2017.08.082","article-title":"miR-124 downregulates BACE 1 and alters autophagy in APP\/PS1 transgenic mice","volume":"280","author":"Du","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1007\/s12035-016-9845-y","article-title":"miR-124 Regulates the Expression of BACE1 in the Hippocampus Under Chronic Cerebral Hypoperfusion","volume":"54","author":"Zhang","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2584940","DOI":"10.1155\/2016\/2584940","article-title":"Differential DNA Methylation of MicroRNA Genes in Temporal Cortex from Alzheimer\u2019s Disease Individuals","volume":"2016","author":"Villela","year":"2016","journal-title":"Neural Plast"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/jcb.26170","article-title":"The Neuroprotective Role of MiR-124-3p in a 6-Hydroxydopamine-Induced Cell Model of Parkinson\u2019s Disease via the Regulation of ANAX5","volume":"119","author":"Dong","year":"2018","journal-title":"J. Cell BioChem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s12017-009-8063-4","article-title":"Gene dysregulation in Huntington\u2019s disease: REST, microRNAs and beyond","volume":"11","author":"Johnson","year":"2009","journal-title":"Neuromolecular Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1101\/gad.1519107","article-title":"The microRNA miR-124 antagonizes the anti-neural REST\/SCP1 pathway during embryonic CNS development","volume":"21","author":"Visvanathan","year":"2007","journal-title":"Genes Dev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/jnc.14229","article-title":"Screening the expression characteristics of several miRNAs in G93A-SOD1 transgenic mouse: Altered expression of miRNA-124 is associated with astrocyte differentiation by targeting Sox2 and Sox9","volume":"145","author":"Zhou","year":"2018","journal-title":"J. Neurochem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.mcn.2009.08.009","article-title":"microRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity","volume":"42","author":"Chandrasekar","year":"2009","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/npp.2010.250","article-title":"Regulation of MiR-124, Let-7d, and MiR-181a in the accumbens affects the expression, extinction, and reinstatement of cocaine-induced conditioned place preference","volume":"36","author":"Chandrasekar","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Bosch, P.J., Benton, M.C., Macartney-Coxson, D., and Kivell, B.M. (2015). mRNA and microRNA analysis reveals modulation of biochemical pathways related to addiction in the ventral tegmental area of methamphetamine self-administering rats. BMC Neurosci., 16.","DOI":"10.1186\/s12868-015-0186-y"},{"key":"ref_97","first-page":"155","article-title":"Epigenetic regulation of MIR-124 under ethanol dependence and withdrawal","volume":"47","author":"Mizuo","year":"2012","journal-title":"Nihon Arukoru Yakubutsu Igakkai Zasshi"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-1-61779-536-7_7","article-title":"Culture of neonatal rodent microglia, astrocytes, and oligodendrocytes from cortex and spinal cord","volume":"846","author":"Skaper","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. 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