{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:08:44Z","timestamp":1784012924641,"version":"3.55.0"},"reference-count":23,"publisher":"Knowledge E DMCC","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["knepublishing.com"],"crossmark-restriction":true},"short-container-title":["JOVR"],"abstract":"<jats:p>Purpose: The endocannabinoid system can suppress inflammatory environment by regulating inflammatory mechanisms in immune and glial cells. Astrocytes secrete soluble inflammatory mediators. Prolonged activation of astrocytes is associated with accelerated aging in the central nervous system. MicroRNAs are increasingly shown to be critical gene regulators during inflammation and gliosis. In this study, we investigated the microRNA changes affected by anandamide (AEA), a dominant endocannabinoid in normal human astrocytes, following exposure to the HIV-1 Tat (Trans-activator of transcription) protein. Methods: We performed global human microRNA profiling in Tat-activated astrocytes on exposure to AEA. To delineate the mechanism of action, we utilized the bioinformatic tools miRWalk, KEGG, and Cytoscape to assess the global microarray data for significantly impacted miRNAs and their gene targets at the mRNA level. Results: Tat-induced activation significantly upregulated 122 miRNAs (P &lt; 0.05) in astrocytes. Conversely, the addition of AEA in activated astrocytes significantly downregulated the expression of 57 miRNAs. Out of 122 miRNAs upregulated by Tat treatment, 37 miRNAs that were common to Tat and Tat+AEA cells showed reversed expression, suggesting these might be the critical miRNAs with a key role in the AEA-induced mitigation of neuroinflammation. Conclusion: Reversed expression of a selected group of miRNAs identifies antagonistic pathways that promote an anti-inflammatory environment. Pathway analysis of these 37 key miRNAs showed gene targets that regulate inflammation and senescence.<\/jats:p>","DOI":"10.18502\/jovr.v21.17666","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T06:37:13Z","timestamp":1784011033000},"page":"1-10","update-policy":"https:\/\/doi.org\/10.18502\/knecrossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Antagonistic Activity of Anandamide on Tat-treated Human Astrocytes Identifies Inflammaging Pathways: Anandamide Affects Aging Pathways"],"prefix":"10.18502","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1433-0556","authenticated-orcid":false,"given":"Durairaj","family":"Duraikannu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-9446","authenticated-orcid":false,"given":"Kamini","family":"Khatak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1004-7091","authenticated-orcid":false,"given":"Hemavathy","family":"Nagarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2695-4668","authenticated-orcid":false,"given":"Sridharan","family":"Sudharshan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-7400","authenticated-orcid":false,"given":"Nivedita","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7770","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"337661","doi-asserted-by":"crossref","unstructured":"1. Lowe H, Toyang N, Steele B, Bryant J, Ngwa W. The endocannabinoid system: A potential target for the treatment of various diseases. Int J Mol Sci 2021;22:9472.","DOI":"10.3390\/ijms22179472"},{"key":"337662","doi-asserted-by":"crossref","unstructured":"2. Tanaka M, Sackett S, Zhang Y. Endocannabinoid modulation of microglial phenotypes in neuropathology. Front Neurol 2020;11:87.","DOI":"10.3389\/fneur.2020.00087"},{"key":"337663","doi-asserted-by":"crossref","unstructured":"3. Molina-Holgado F, Lled\u00f3 A, Guaza C. Anandamide suppresses nitric oxide and TNF-\u03b1 responses to Theiler\u2019s virus or endotoxin in astrocytes. Neuroreport 1997;8:1929-1933.","DOI":"10.1097\/00001756-199705260-00027"},{"key":"337664","doi-asserted-by":"crossref","unstructured":"4. Ilyasov AA, Milligan CE, Pharr EP, Howlett AC. The endocannabinoid system and oligodendrocytes in health and disease. 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CXCL13 as a biomarker of immune activation during early and chronic HIV infection. Front Immunol 2019;10:289.","DOI":"10.3389\/fimmu.2019.00289"},{"key":"337669","doi-asserted-by":"crossref","unstructured":"9. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010;11:597-610.","DOI":"10.1038\/nrg2843"},{"key":"337670","doi-asserted-by":"crossref","unstructured":"10. O\u2019Neill LA, Sheedy FJ, McCoy CE. MicroRNAs: The finetuners of Toll-like receptor signalling. Nat Rev Immunol 2011;11:163-175.","DOI":"10.1038\/nri2957"},{"key":"337671","doi-asserted-by":"crossref","unstructured":"11. Sultan M, Alghetaa H, Mohammed A, Abdulla OA, Wisniewski PJ, Singh N, et al. The endocannabinoid anandamide attenuates acute respiratory distress syndrome by downregulating miRNA that target inflammatory pathways. Front Pharmacol 2021;12:644281.","DOI":"10.3389\/fphar.2021.644281"},{"key":"337672","doi-asserted-by":"crossref","unstructured":"12. Rahimian P, He JJ. HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression. J Neuroinflammation 2016;13:247.","DOI":"10.1186\/s12974-016-0716-2"},{"key":"337673","doi-asserted-by":"crossref","unstructured":"13. Doke M, Jeganathan V, McLaughlin JP, Samikkannu T. HIV-1 Tat and cocaine impact mitochondrial epigenetics: Effects on DNA methylation. Epigenetics 2021;16:980-999.","DOI":"10.1080\/15592294.2020.1834919"},{"key":"337674","doi-asserted-by":"crossref","unstructured":"14. Doke M, McLaughlin JP, Cai JJ, Pendyala G, Kashanchi F, Khan MA, et al. HIV-1 Tat and cocaine impact astrocytic energy reservoirs and epigenetic regulation by influencing the LINC01133-hsa-miR-4726-5p-NDUFA9 axis. Mol Ther Nucleic Acids 2022;29:243-258.","DOI":"10.1016\/j.omtn.2022.07.001"},{"key":"337675","doi-asserted-by":"crossref","unstructured":"15. Henry CJ, Huang Y, Wynne AM, Godbout JP. Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1\u03b2 and anti-inflammatory IL-10 cytokines. Brain Behav Immun 2009;23:309-317.","DOI":"10.1016\/j.bbi.2008.09.002"},{"key":"337676","doi-asserted-by":"crossref","unstructured":"16. Huang Y, Henry CJ, Dantzer R, Johnson RW, Godbout JP. Exaggerated sickness behavior and brain proinflammatory cytokine expression in aged mice in response to intracerebroventricular lipopolysaccharide. Neurobiol Aging 2008;29:1744-1753.","DOI":"10.1016\/j.neurobiolaging.2007.04.012"},{"key":"337677","doi-asserted-by":"crossref","unstructured":"17. Boehm M, Slack F. A developmental timing microRNA and its target regulate life span in C. elegans. 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