Antagonistic activity of AEA on TAT treated Human Astrocytes identify Inflammaging pathways

Abstract

Physiologically, the endocannabinoids are known to reduce inflammation by decreasing production of inflammatory factors in immune and glial cells. Astrocytes secrete soluble inflammatory mediators and prolonged activation of astrocytes is associated with accelerated aging in Central Nervous System. Many reports show miRNAs as critical gene regulators in inflammation and astrogliosis in astrocytes. The aim of this study is to investigate the microRNA changes affected by Anandamide on HIV1 TAT (Trans-activator of transcription protein) stimulated normal human astrocytes. We performed global microRNA profile in TAT activated astrocytes and analysed changes on exposure to AEA. To delineate the mechanism of action we assessed with bioinformatic tools miRWalk, KEGG and Cytoscape the global microarray for significantly impacted miRNAs, and their gene targets. TAT activation in astrocytes upregulated 122 miRNAs significantly (p < 0.05). Addition of AEA in activated astrocytes downregulate the expression of 57 miRNAs significantly. Out of 122 upregulated miRNAs on TAT treatment, 37 miRNAs which were common in TAT and TAT+AEA cells showed reversal suggesting clues to critical miRNAs for the AEA-induced mitigation of neuroinflammation. Reversal in expression of selected group of miRNAs identify antagonistic pathways which are promoting anti-inflammatory environment. Pathway analysis of key 37 miRNAs show gene targets that regulate inflammation and senescence.