Activation of Myenteric Glia during Acute Inflammation In Vitro and In Vivo

Area of Science:

• Neuroscience
• Gastroenterology
• Immunology

Background:

• Enteric glial cells (EGCs) are key components of the enteric nervous system, similar to astrocytes.
• EGCs react to inflammatory conditions, but research primarily focuses on mucosal inflammation in Inflammatory Bowel Disease (IBD).
• Little is known about how systemic inflammation affects the entire EGC network beyond the mucosa.

Purpose of the Study:

• To investigate the impact of systemic lipopolysaccharide (LPS)-induced hyperinflammation on EGCs in vivo.
• To analyze the effects on both the small and large intestine's EGC network.
• To understand the specific role of Glial Fibrillary Acidic Protein (GFAP)-expressing EGCs in systemic inflammation.

Main Methods:

• Used a rat model to induce systemic inflammation via LPS injection.
• Analyzed intestinal tissues at transcript and protein levels 4 hours post-LPS injection.
• Employed laser capture microdissection for plexus-specific gene expression analysis.
• Established primary glial cell cultures from GFAP-EGFP reporter mice for in vitro studies.
• Performed cytokine secretion analysis and global gene expression profiling, followed by bioinformatic comparative transcriptome analysis.

Main Results:

• Systemic LPS injection caused rapid, localized activation of GFAP-expressing EGCs at the mRNA level in the myenteric plexus.
• Primary cultures of GFAP+ EGCs secreted increased inflammatory cytokines after LPS stimulation.
• A significant shift in myenteric glial gene expression was observed, primarily affecting immune response genes.

Conclusions:

• The myenteric GFAP-expressing glial subpopulation is highly susceptible and responsive to acute systemic gut inflammation.
• These findings expand our understanding of glial cell involvement in systemic intestinal inflammation, complementing existing knowledge on mucosal inflammation.