Dexmedetomidine inhibits inflammation in microglia cells under stimulation of LPS and ATP by c-Fos/NLRP3/caspase-1 cascades

Hu, Li; Zhang, Xueping; Chen, Mingfu; Chen, Jianyan; Gao, Tao; Yao, Shanglong

doi:10.17179/excli2017-1018

Cited by 28 publications

(14 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This alteration is associated with restoring the abnormal microglial phenotype and attenuation of the disease [ 76 ]. While some studies show that c-Fos suppresses the expression of pro-inflammatory phenotype-associated genes, such as inducible NO synthase ( iNOS ) [ 77 ], tumor necrosis factor-alpha ( Tnfα ), and Il-6 through the suppression of NF-k

activity [ 78 ], suggesting that it acts as an anti-inflammatory transcription factor essential for microglia survival [ 76 , 78 ], other studies show that the blockade of c-Fos with dexmedetomidine halts microglia inflammation and inhibits postoperative cognitive dysfunction in AD patients, thus setting c-Fos as a potential anti-inflammatory therapeutic target for NDs [ 79 ]. Regarding the Gsk3

, its activation is associated with increased neuroinflammation and microglial activation.…”

Section: Discussionmentioning

confidence: 99%

Profiling Microglia in a Mouse Model of Machado–Joseph Disease

et al. 2022

View full text Add to dashboard Cite

Microglia have been increasingly implicated in neurodegenerative diseases (NDs), and specific disease associated microglia (DAM) profiles have been defined for several of these NDs. Yet, the microglial profile in Machado–Joseph disease (MJD) remains unexplored. Here, we characterized the profile of microglia in the CMVMJD135 mouse model of MJD. This characterization was performed using primary microglial cultures and microglial cells obtained from disease-relevant brain regions of neonatal and adult CMVMJD135 mice, respectively. Machine learning models were implemented to identify potential clusters of microglia based on their morphological features, and an RNA-sequencing analysis was performed to identify molecular perturbations and potential therapeutic targets. Our findings reveal morphological alterations that point to an increased activation state of microglia in CMVMJD135 mice and a disease-specific transcriptional profile of MJD microglia, encompassing a total of 101 differentially expressed genes, with enrichment in molecular pathways related to oxidative stress, immune response, cell proliferation, cell death, and lipid metabolism. Overall, these results allowed us to define the cellular and molecular profile of MJD-associated microglia and to identify genes and pathways that might represent potential therapeutic targets for this disorder.

show abstract

, its activation is associated with increased neuroinflammation and microglial activation.…”

Section: Discussionmentioning

confidence: 99%

Profiling Microglia in a Mouse Model of Machado–Joseph Disease

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The immediate early gene product c-Fos has been widely used as an indirect marker of cell (neurons as well as other cell types) activation in response to nutrient and hormonal signals such as glucose [ 58 , 59 ]. Intriguingly, a recent study demonstrated that c-Fos expression was increased in response to LPS/ATP treatment in HMC3 microglial cells [ 60 ]. Another study reported that a high concentration of glucose increases phosphorylation of ERK1/2 in BV-2 microglia [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Regulation of the Fructose Transporter Gene Slc2a5 Expression by Glucose in Cultured Microglial Cells

Mizuno

Lew

Jhanji

2021

IJMS

View full text Add to dashboard Cite

Microglia play a role in the regulation of metabolism and pathogenesis of obesity. Microglial activity is altered in response to changes in diet and the body’s metabolic state. Solute carrier family 2 member 5 (Slc2a5) that encodes glucose transporter 5 (GLUT5) is a fructose transporter primarily expressed in microglia within the central nervous system. However, little is known about the nutritional regulation of Slc2a5 expression in microglia and its role in the regulation of metabolism. The present study aimed to address the hypothesis that nutrients affect microglial activity by altering the expression of glucose transporter genes. Murine microglial cell line SIM-A9 cells and primary microglia from mouse brain were exposed to different concentrations of glucose and levels of microglial activation markers and glucose transporter genes were measured. High concentration of glucose increased levels of the immediate-early gene product c-Fos, a marker of cell activation, Slc2a5 mRNA, and pro-inflammatory cytokine genes in microglial cells in a time-dependent manner, while fructose failed to cause these changes. Glucose-induced changes in pro-inflammatory gene expression were partially attenuated in SIM-A9 cells treated with the GLUT5 inhibitor. These findings suggest that an increase in local glucose availability leads to the activation of microglia by controlling their carbohydrate sensing mechanism through both GLUT5-dependent and –independent mechanisms.

show abstract

“…It is known that microglial NOD-like receptor 3 (NLRP3) is associated with neuroinflammation and is also a therapeutic target in Alzheimer’s disease. Thus, the anti-inflammatory effects of dexmedetomidine inhibit NLRP3-derived inflammasome, modulating the c-fos upregulated expression [ 155 ]. As in other glial types, there is also evidence showing that LPS can induce the expression of c-fos in microglia and the consequent inflammation in the brain [ 156 ].…”

Section: C-fos and Glial Cells: Evidence And Perspectivesmentioning

confidence: 99%

Immediate Early Gene c-fos in the Brain: Focus on Glial Cells

et al. 2022

View full text Add to dashboard Cite

The c-fos gene was first described as a proto-oncogene responsible for the induction of bone tumors. A few decades ago, activation of the protein product c-fos was reported in the brain after seizures and other noxious stimuli. Since then, multiple studies have used c-fos as a brain activity marker. Although it has been attributed to neurons, growing evidence demonstrates that c-fos expression in the brain may also include glial cells. In this review, we collect data showing that glial cells also express this proto-oncogene. We present evidence demonstrating that at least astrocytes, oligodendrocytes, and microglia express this immediate early gene (IEG). Unlike neurons, whose expression changes used to be associated with depolarization, glial cells seem to express the c-fos proto-oncogene under the influence of proliferation, differentiation, growth, inflammation, repair, damage, plasticity, and other conditions. The collected evidence provides a complementary view of c-fos as an activity marker and urges the introduction of the glial cell perspective into brain activity studies. This glial cell view may provide additional information related to the brain microenvironment that is difficult to obtain from the isolated neuron paradigm. Thus, it is highly recommended that detection techniques are improved in order to better differentiate the phenotypes expressing c-fos in the brain and to elucidate the specific roles of c-fos expression in glial cells.

show abstract

Dexmedetomidine inhibits inflammation in microglia cells under stimulation of LPS and ATP by c-Fos/NLRP3/caspase-1 cascades

Cited by 28 publications

References 26 publications

Profiling Microglia in a Mouse Model of Machado–Joseph Disease

Profiling Microglia in a Mouse Model of Machado–Joseph Disease

Regulation of the Fructose Transporter Gene Slc2a5 Expression by Glucose in Cultured Microglial Cells

Immediate Early Gene c-fos in the Brain: Focus on Glial Cells

Contact Info

Product

Resources

About