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Updated: Jun 8, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Activated microglia secretome and proinflammatory cytokines increase neuronal mu-opioid receptor signalling and
Javier Cuitavi1, Pere Duart-Abadia2, Julie Sanchez3
1Instituto de Biotecnología y Biomedicina (BIOTECMED), University of Valencia, Burjassot, Spain; Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Burjassot, Spain.
Abstract:
Due to its potential role in processes which rely on mu-opioid receptor function, investigating the relationship between Mu-Opioid receptors (MORs), neuroinflammation, and glial cells has gained momentum. Traditionally, MOR activation has been associated with immunosuppression, but recent findings suggest a more nuanced, bidirectional relationship with the immune system. To further investigate this relationship, herein, we investigated the role of the activated microglia secretome and proinflammatory cytokines in neuronal MOR expression and signalling. Our results show that both microglial secretome and specific cytokines increase neuronal MOR expression and enhance the [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO)-induced MOR activation. We also show that DAMGO-induced neuroinflammation increases neuronal MOR expression, activation, and regulation. Our findings suggest a feedback loop between microglial activation, cytokine release, and neuronal MOR dynamics. Future research should delve into the temporal dynamics and functional implications of this relationship, particularly concerning clinically relevant opioids like morphine and fentanyl and pain management.
Insights
Neuroinflammation and microglia activation enhance neuronal mu-opioid receptor (MOR) expression and signaling. This suggests a feedback loop influencing opioid responses and pain management.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- The relationship between mu-opioid receptors (MORs), neuroinflammation, and glial cells is under active investigation.
- While traditionally linked to immunosuppression, MOR activation exhibits a complex, bidirectional interaction with the immune system.
Purpose of the Study:
- To explore the impact of activated microglia secretome and proinflammatory cytokines on neuronal MOR expression and signaling.
- To elucidate the role of microglial activation in modulating neuronal opioid receptor dynamics.
Main Methods:
- Investigated the effects of microglial secretome and specific cytokines on neuronal MOR expression.
- Assessed the influence of [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) on MOR activation and neuroinflammation.
- Examined the impact of DAMGO-induced neuroinflammation on neuronal MOR expression, activation, and regulation.
Main Results:
- Both microglial secretome and proinflammatory cytokines significantly increased neuronal MOR expression.
- These factors enhanced DAMGO-induced MOR activation.
- DAMGO-induced neuroinflammation led to increased neuronal MOR expression, activation, and regulation.
Conclusions:
- A feedback loop exists between microglial activation, cytokine release, and neuronal MOR dynamics.
- Findings highlight a novel interaction influencing opioid receptor function in the context of neuroinflammation.
- Further research is needed to understand the implications for clinically relevant opioids and pain management.
