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

• DOI: 10.7554/elife.97916
• Publication Date: 2024-06-03T18:25:07Z
• Authors: Jeffrey Barr; Austin Walz; Anthony C Restaino; Moran Amit; Sarah M Barclay; Elisabeth G Vichaya; William C Spanos; Robert Dantzer; Sebastien Talbot; Paola D Vermeer
• Keywords: Nociceptor; Brain tumor; Calcium imaging; Premovement neuronal activity

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 mouse model for head and neck cancer neuronal tracing, we show that tumor-infiltrating connect distinct areas. The activation of this circuitry altered behaviors (decreased nest-building, increased latency eat cookie, reduced wheel running). Tumor-infiltrating nociceptor neurons exhibited heightened calcium activity regions receiving neural projections showed elevated Fos as well responses compared non-tumor-bearing counterparts. genetic elimination decreased expression mitigated the behavioral induced presence tumor. While analgesic treatment restored nesting cookie test behaviors, it did not fully restore voluntary running indicating pain is exclusive driver such shifts. Unraveling interaction between tumor, nerves, pivotal developing targeted interventions alleviate health burdens associated with cancer.