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In vivo indomethacin treatment causes microglial activation in adult mice
M M Prechel1, C Ding, R L Washington
1Department of Pathology, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA. mpreche@wpo.it.luc.edu
Abstract:
The current study was undertaken to study the role of prostaglandins in regulating microglial activation. Mice were treated with indomethacin (2 microg/ml) in their drinking water to selectively inhibit cyclooxygenase activity. After 4-8 days, the effect of inhibiting prostaglandin synthesis on microglial activity was evaluated. This was accomplished by analyzing microglial expression of Mac-1 (C3 complement receptor) as an indicator of activation. Mac-1 expression was assessed by immunohistochemistry of fixed brain cryosections, and by flow cytometric analysis of immunostained single cell suspensions. Both methods demonstrated that compared to age-matched, untreated controls, brains of indomethacin-treated mice had increased levels of Mac-1 expression, suggesting an increase in the state of microglial activation. These results demonstrate the importance of prostaglandins in down regulating microglial activity, and that inhibition of prostaglandin synthesis with indomethacin may act to increase the reactivity of the brain's immune system.
Insights
Prostaglandins normally reduce microglial activation. Inhibiting prostaglandin synthesis with indomethacin increased microglial activation, indicating prostaglandins are crucial for regulating the brain's immune response.
Area of Science:
- Neuroimmunology
- Molecular Biology
Background:
- Microglia are the primary immune cells of the central nervous system.
- Prostaglandins are signaling molecules with diverse physiological roles, including immune modulation.
- Dysregulated microglial activation is implicated in various neurological disorders.
Purpose of the Study:
- To investigate the role of prostaglandins in regulating microglial activation.
- To determine if inhibiting prostaglandin synthesis affects microglial activation markers.
Main Methods:
- Mice were treated with indomethacin to inhibit cyclooxygenase (COX) activity and prostaglandin synthesis.
- Microglial activation was assessed by quantifying Mac-1 (C3 complement receptor) expression.
- Mac-1 levels were measured using immunohistochemistry and flow cytometry.
Main Results:
- Indomethacin treatment led to significantly increased Mac-1 expression in the brains of mice compared to controls.
- This suggests a higher state of microglial activation in prostaglandin-synthesis-inhibited mice.
- Both immunohistochemistry and flow cytometry confirmed these findings.
Conclusions:
- Prostaglandins play a critical role in down-regulating microglial activity.
- Inhibition of prostaglandin synthesis, for example with indomethacin, can enhance microglial activation.
- These findings highlight the importance of prostaglandins in maintaining immune homeostasis in the brain.