Attenuation of microglial aryl hydrocarbon receptor alters astrocyte activation and chronic pain sensitization in aging

Area of Science:

• Neuroscience
• Immunology
• Aging Research

Background:

• Microglia play a crucial role in neuroinflammation and pain sensitization.
• Aryl hydrocarbon receptor (AHR) signaling is implicated in immune cell function.
• Age-related changes in microglial function contribute to chronic pain.

Purpose of the Study:

• To compare aryl hydrocarbon receptor (AHR) expression in microglia from aged versus adult mice.
• To investigate the role of microglial AHR in chronic pain sensitization.
• To determine the impact of microglial AHR attenuation on astrocyte activation and neuroinflammation.

Main Methods:

• Immunofluorescence staining to quantify AHR expression in microglia.
• In vitro treatment of BV2 microglial cells with LPS, AHR agonist (FICZ), and antagonist (CH223191).
• Co-culture of treated microglia supernatant with C8-DIA astrocytes and quantification of inflammatory factors via qPCR.

Main Results:

• AHR expression in spinal dorsal horn microglia was significantly reduced in aged mice compared to adult mice.
• Diminished microglial AHR expression led to increased astrocyte activation.
• Activated microglia with reduced AHR expression enhanced astrocyte-mediated inflammation, contributing to prolonged hyperalgesia.

Conclusions:

• Reduced microglial AHR expression in aged mice is associated with heightened neuroinflammation and chronic pain.
• Microglial AHR signaling modulates astrocyte activation and inflammatory responses.
• Targeting microglial AHR may offer a therapeutic strategy for age-related chronic pain.