Tumor-Infiltrating Nerves Functionally Alter Brain Circuits and Modulate Behavior in a Mouse Model of Head-and-Neck Cancer

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

Publication Date

9-20-2024

Journal

eLife

Abstract

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 and neuronal tracing, we show that tumor-infiltrating nerves connect to distinct brain areas. The activation of this neuronal circuitry altered behaviors (decreased nest-building, increased latency to eat a cookie, and reduced wheel running). Tumor-infiltrating nociceptor neurons exhibited heightened calcium activity and brain regions receiving these neural projections showed elevated Fos as well as increased calcium responses compared to non-tumor-bearing counterparts. The genetic elimination of nociceptor neurons decreased brain Fos expression and mitigated the behavioral alterations induced by the presence of the tumor. While analgesic treatment restored nesting and cookie test behaviors, it did not fully restore voluntary wheel running indicating that 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.

Keywords

Animals, Mice, Disease Models, Animal, Head and Neck Neoplasms, Brain, Behavior, Animal, Neurons, Mice, Inbred C57BL, Male

DOI

10.7554/eLife.97916

PMID

39302290

PMCID

PMC11415076

PubMedCentral® Posted Date

9-20-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes