Journal article
Inhibition of DNA methylation with zebularine alters lipopolysaccharide-induced neuroinflammation in mice
Brain, behavior, and immunity, v 66, e37
Nov 2017
Abstract
Inhibitors of DNA methyltransferases (DNMTs), the enzymes that catalyze DNA methylation, alter DNA methylation globally in the brain and at individual neural plasticity-associated genes. This suggests that DNA methylation is dynamically regulated in the brain, but how DNMT inhibitors centrally influence lipopolysaccharide (LPS)-induced neuroinflammation is not known. Specifically, we sought to determine if zebularine would alter DNA methylation of the Il1b promoter as well as expression of inflammatory genes in the hippocampus and microglia. Adult 3–6month-old C57BL/6J mice were implanted with an intracerebroventricular (ICV) cannula, and after 7days of recovery were injected ICV with saline or the DNMT inhibitor zebularine (300ng/ul). LPS (10ng/ul) or saline was injected ICV 30min later. Using bisulfite pyrosequencing, novel findings indicate that ICV zebularine led to decreased DNA methylation of one of the CpG sites near the Il1b proximal promoter alone or in combination with LPS (p<0.05). Additionally, mice given both zebularine and LPS had similar pro-inflammatory gene expression compared to only LPS-treated mice in the hippocampus at 48h (p>0.05). Ongoing work will assess treatment effects 4h post-injection when inflammation is expected to be maximal. Taken together, these data suggest that modulation of DNA methylation with a DNMT inhibitor in the brain can affect molecular mechanisms of neuroinflammation. Supported by NIH AG016710.
Metrics
4 Record Views
Details
- Title
- Inhibition of DNA methylation with zebularine alters lipopolysaccharide-induced neuroinflammation in mice
- Creators
- S.M. Matt - University of Illinois Urbana-ChampaignJ.D. Zimmerman - University of Illinois Urbana-ChampaignM.A. Lawson - University of Illinois Urbana-ChampaignA.C. Bustamante - University of Illinois Urbana-ChampaignM. Uddin - University of Illinois Urbana-ChampaignR.W. Johnson - University of Illinois Urbana-Champaign
- Publication Details
- Brain, behavior, and immunity, v 66, e37
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Other Identifier
- 991021902505604721