Activated Microglia Mediate the Motor Neuron-, Synaptic Denervation- and Muscle Wasting-Changes in Burn Injured Mice

Area of Science:

• Neuroscience
• Immunology
• Regenerative Medicine

Background:

• Muscle wasting (MW) following burn injury (BI) is a significant clinical challenge.
• Microglia-mediated inflammation and motor neuron loss (MNL) are implicated in BI-induced MW, but the precise connections remain unclear.
• Microglia express α7 acetylcholine receptors (α7AChRs), which can modulate inflammatory responses.

Purpose of the Study:

• To investigate the role of microglia-mediated inflammation in burn injury-induced motor neuron loss and muscle wasting.
• To determine if stimulating α7AChRs can mitigate these pathological changes.

Main Methods:

• Wild-type and α7AChR knockout mice were subjected to burn injury (BI) or sham injury (SB).
• Mice were treated with or without the α7AChR agonist GTS-21.
• Spinal cord and muscle tissues were analyzed for microglial activation, motor neuron survival, synaptic integrity, inflammatory markers, and muscle mass.

Main Results:

• BI induced significant microgliosis, motor neuron loss, synaptic denervation, and muscle wasting in wild-type mice.
• α7AChR knockout exacerbated motor neuron loss and inflammatory responses.
• GTS-21 treatment significantly reduced inflammation, motor neuron loss, synaptic denervation, and muscle wasting in wild-type mice but had no effect in knockout mice.

Conclusions:

• Microglia-mediated inflammation plays a critical role in burn injury-induced motor neuron loss and muscle wasting.
• Targeting α7AChRs with agonists like GTS-21 can effectively mitigate these detrimental effects.
• α7AChRs are important for maintaining spinal cord homeostasis, even in the absence of injury.