| Autor: |
Warren D. Anderson, Andrew D. Greenhalgh, Aditya Takwale, Samuel David, Rajanikanth Vadigepalli |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Frontiers in Cellular Neuroscience, Vol 11 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
1662-5102 |
| DOI: |
10.3389/fncel.2017.00233 |
| Popis: |
Coordinated interactions between cytokine signaling and morphological dynamics of microglial cells regulate neuroinflammation in CNS injury and disease. We found that pro-inflammatory cytokine gene expression in vivo showed a pronounced recovery following systemic LPS. We performed a novel multivariate analysis of microglial morphology and identified changes in specific morphological properties of microglia that matched the expression dynamics of pro-inflammatory cytokine TNFα. The adaptive recovery kinetics of TNFα expression and microglial soma size showed comparable profiles and dependence on anti-inflammatory cytokine IL-10 expression. The recovery of cytokine variations and microglial morphology responses to inflammation were negatively regulated by IL-10. Our novel morphological analysis of microglia is able to detect subtle changes and can be used widely. We implemented in silico simulations of cytokine network dynamics which showed—counter-intuitively, but in line with our experimental observations—that negative feedback from IL-10 was sufficient to impede the adaptive recovery of TNFα-mediated inflammation. Our integrative approach is a powerful tool to study changes in specific components of microglial morphology for insights into their functional states, in relation to cytokine network dynamics, during CNS injury and disease. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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