Protein arginine methyltransferase-1 deficiency restrains depression-like behavior of mice by inhibiting inflammation and oxidative stress via Nrf-2.

Abstract

Current evidence indicates that depression is accompanied by the activation of inflammatory response and oxidative stress. Protein arginine methyltransferase 1 (PRMT1) is a histone methyltransferase that methylates Arg3 on histone H4, playing crucial role in regulating various pathological processes. In the study, we attempted to explore the effects of PRMT1 on animal model with depression through a single administration of lipopolysaccharide (LPS). Our results indicated that PRMT1 knockout (PRMT1-/-) improved LPS-induced anxiety- and depressive-like behavior, along with up-regulated expression levels of brain-derived neurotrophic factor (BDNF) and PSD-95. Furthermore, PRMT1 deficiency significantly improved LPS-induced changes in dendritic spine density in the areas of prefrontal cortex (PFC), CA3 and dentate gyrus (DG), and nucleus accumbens (NAc). In addition, PRMT1 deletion ameliorated the neuroinflammatory responses, as evidenced by the reduced expression of interleukin 1β (IL-1β) and tumor necrosis factor (TNF)-α, which might be through repressing nuclear factor-κB (NF-κB) signaling. Moreover, oxidative stress induced by LPS was alleviated by PRMT1 knockout in hippocampus of mice at least partly via promoting Nrf-2 expressions. The anti-depressant effects of PRMT1 inhibition were verified in LPS-incubated astrocytes. Importantly, we found that PRMT1 knockout-alleviated inflammation and oxidative stress triggered by LPS were significantly recovered by the suppression of Nrf-2. Therefore, Nrf-2 was markedly involved in PRMT1-regulated depression-like behavior. Taken together, the results indicated that PRMT1 might be an important therapeutic target for developing effective treatment to prevent depressive-like behavior.

• Authors: Hongbo Liu, Jinghui Jiang, Lili Zhao
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 518 Issue 3 Pg. 430-437 (10 20 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31492498 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Lipopolysaccharides
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Prmt1 protein, mouse
• Protein-Arginine N-Methyltransferases

Topics

• Animals
• Anxiety (genetics, immunology, pathology)
• Depression (genetics, immunology, pathology)
• Gene Deletion
• Inflammation (genetics, immunology, pathology)
• Lipopolysaccharides (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NF-E2-Related Factor 2 (genetics, immunology)
• Oxidative Stress
• Protein-Arginine N-Methyltransferases (genetics, immunology)
• Up-Regulation