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

Autor:	Barr J; Sanford Research, Cancer Biology and Immunotherapies Group, Sioux Falls, Sioux Falls, United States., Walz A; Sanford Research, Cancer Biology and Immunotherapies Group, Sioux Falls, Sioux Falls, United States., Restaino AC; Sanford Research, Cancer Biology and Immunotherapies Group, Sioux Falls, Sioux Falls, United States.; University of South Dakota, Sanford School of Medicine, Vermillion, United States., Amit M; University of Texas, MD Anderson Cancer Center, Houston, United States., Barclay SM; Sanford Research, Cancer Biology and Immunotherapies Group, Sioux Falls, Sioux Falls, United States., Vichaya EG; Baylor University, Department of Psychology and Neuroscience, Waco, United States., Spanos WC; Sanford Research, Cancer Biology and Immunotherapies Group, Sioux Falls, Sioux Falls, United States.; University of South Dakota, Sanford School of Medicine, Vermillion, United States., Dantzer R; University of Texas, MD Anderson Cancer Center, Houston, United States., Talbot S; Queen's University, Department of Biomedical and Molecular Sciences, Kingston, Canada., Vermeer PD; Sanford Research, Cancer Biology and Immunotherapies Group, Sioux Falls, Sioux Falls, United States.; University of South Dakota, Sanford School of Medicine, Vermillion, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Sep 20; Vol. 13. Date of Electronic Publication: 2024 Sep 20.
DOI:	10.7554/eLife.97916
Abstrakt:	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. Competing Interests: JB, AW, AR, MA, SB, EV, WS, RD, ST, PV No competing interests declared (© 2024, Barr, Walz et al.)
Databáze:	MEDLINE
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