PGC-1α-Mediated Mitochondrial Biogenesis is Involved in Cannabinoid Receptor 2 Agonist AM1241-Induced Microglial Phenotype Amelioration.

Abstract

Cannabinoid type 2 receptor (CB2R) agonist AM1241 induces anti-inflammation by ameliorating microglial phenotypes, the mechanism, however, is still unknown. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcription protein which can regulate mitochondrial biogenesis, and the aim of this study is to investigate whether PGC-1α is involved in AM1241-induced anti-inflammation in N9 microglial cells. We used 10 ng/ml lipopolysaccharide (LPS) plus 10 U/ml interferon γ (IFNγ) to activate microglia into classic activated phenotype (M1 phenotype), and found that co-administration of 10 µM AM1241 increased the expressions of mitochondria biogenesis-associated proteins, including nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM) and COX IV, and up-regulated the biomarker levels of microglial M2 phenotype, including arginase 1 (Arg-1) and brain-derived neurotrophic factor (BDNF), and down-regulated biomarker levels of M1 phenotype, including inducible nitric oxide synthase (iNOS) and tumor necrosis factor α (TNF-α), compared to the cells treated with LPS plus IFNγ only (P < 0.05). By using PGC-1α-siRNA, however, we found that down-regulation of PGC-1α significantly reversed the AM1241-induced effects above (P < 0.05). According to the results in this study, we found that PGC-1α may mediate CB2R agonist AM1241-induced anti-inflammation in N9 microglial cells, and the mechanism might be associated with the enhancement of mitochondria biogenesis.

• Authors: Lei Ma, Wen Niu, Jianrui Lv, Ji Jia, Miaozhang Zhu, Shuai Yang
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 38 Issue 8 Pg. 1529-1537 (Nov 2018) ISSN: 1573-6830 [Electronic] United States
• PMID: 30315387 (Publication Type: Journal Article)

Chemical References

• AM 1241
• Cannabinoids
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• RNA, Small Interfering
• Receptor, Cannabinoid, CB2

Topics

• Animals
• Cannabinoids (pharmacology)
• Cell Line
• Energy Metabolism (drug effects)
• Microglia (drug effects, metabolism, ultrastructure)
• Mitochondria (drug effects, metabolism, ultrastructure)
• Organelle Biogenesis
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (metabolism)
• Phenotype
• RNA, Small Interfering (metabolism)
• Rats
• Receptor, Cannabinoid, CB2 (agonists)