Cocaine-Mediated Microglial Activation Involves Epigenetic Dysregulation of DNMT1/INCRNA XIST/PPARG Signaling Axis
Led by Dr. Palsamy PeriyasamyUniversity of Nebraska-Lincoln
Study Overview:
This project aims to research whether cocaine activates the microglia via lncRNA Xist-DNMT1-mediated epigenetic promoter DNA hypermethylation of PPARG, thereby resulting in elevated secretion of proinflammatory cytokines.
Specific Aims:
(Aim 1): To determine the epigenetic mechanism(s) underlying cocaine-mediated microglial activation in vitro.
(Aim 2): To validate the epigenetic mechanism(s) underlying cocaine-mediated microglial activation in vivo.
Study Sample Population:
N=20 (pregnant C57BI/6 wild-type mouse dams - and their newborn pups); N=48 (C57BL/6 wild-type mouse, 8-weeks-old).
Unique Study Procedures:
None.
Long-Term Goals:
Findings from this proposal will provide evidence that noncoding RNAs and epigenetic mechanisms play critical roles in the cocaine abuse-mediated neuroinflammation. Also, the proposal outcome will provide robust preliminary data for the successful submission of an R01 grant in early 2022. Understanding the mechanisms responsible for microglial activation induced by cocaine will set the stage for the future development of novel therapeutic targets aimed at dampening the neuroinflammatory responses caused by drug addiction.
Dr. Palsamy PeriyasamyPROJECT Director
Dr. Palsamy Periyasamy is an Assistant Professor in the Department of Pharmacology and Experimental Neuroscience, UNMC. His long-term goal is to investigate the epigenetic changes that occurred during HIV-1 infection and drug abuse leading to glial cell activation and to identify potential therapeutic strategies for HIV-associated neurocognitive disorder (HAND) treatment.