Exp Neurobiol.  2025 Feb;34(1):34-47. 10.5607/en24016.

Neuroinflammation in Adaptive Immunodeficient Mice with Colitis-like Symptoms

• Park SH
• Kang J
• Lee JY
• Yoon JS
• Hwang SH
• Lee JY
• Gupta DP
• Baek IH
• Han KJ
• Song GJ

• KMID: 2565916
• DOI: http://doi.org/10.5607/en24016

Abstract

Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis. Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Keyword

Neuroinflammation; IBD; Colitis; Adaptive immunodeficient mice; Brain-gut crosstalk