Enteric neuro-immune interactions in intestinal health and disease

van Baarle, Lies; Stakenborg, Michelle; Matteoli, Gianluca

doi:10.1016/j.smim.2023.101819

Cited by 8 publications

(1 citation statement)

References 143 publications

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“…Neuro-immune interactions have been studied in the context of a variety of conditions including, but not limited to infection 108 , inflammation 109,110 , homeostasis in the gut 111–113 , as well as neurological diseases 114,115 . Neuro-immune communications in the context of cancer and behavior have also been studied (e.g., sickness behavior, depression) 116–118 however, these studies did not assess these interactions at the tumor bed.…”

Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating nerves functionally alter brain circuits and modulate behavior in a mouse model of head-and-neck cancer

Barr,

Walz,

Restaino

et al. 2023

Preprint

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Cancer patients often experience changes in mental health, prompting an exploration into whether nerves infiltrating tumors contribute to these alterations by impacting brain functions. Using a male mouse model for head and neck cancer, we utilized neuronal tracing techniques and show that tumor-infiltrating nerves indeed connect to distinct brain areas via the ipsilateral trigeminal ganglion. The activation of this neuronal circuitry led to behavioral alterations represented by decreased nest-building, increased latency to eat a cookie, and reduced wheel running. Tumor-infiltrating nociceptor neurons exhibited heightened activity, as indicated by increased calcium mobilization. Correspondingly, the specific brain regions receiving these neural projections showed elevated cFos and delta FosB expression in tumor-bearing mice, alongside markedly intensified calcium responses compared to non-tumor-bearing counterparts. The genetic elimination of nociceptor neurons in tumor-bearing mice led to decreased brain Fos expression and mitigated the behavioral alterations induced by the presence of the tumor. While antalgic treatment successfully restored behaviors involving oral movements to normalcy in tumor-bearing mice, it did not have a similar therapeutic effect on voluntary wheel running. This discrepancy points towards an intricate relationship, where pain is not the exclusive driver of such behavioral shifts. Unraveling the interaction between the tumor, infiltrating nerves, and the brain is pivotal to developing targeted interventions to alleviate the mental health burdens associated with cancer.

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