Environmental Enrichment Induces Pericyte and IgA-Dependent Wound Repair and Lifespan Extension in a Colon Tumor Model

Abstract

Summary Environmental enrichment (EE) replicates mind-body therapy by providing complex housing to laboratory animals to improve their activity levels, behavior and social interactions. Using a Tcf4Het/+ ApcMin/+-mediated model of colon tumorigenesis, we found that EE vastly improved the survival of tumor-bearing animals, with differential effect on tumor load in male compared to female animals. Analysis of Tcf4Het/+ ApcMin/+ males showed drastically reduced expression of circulating inflammatory cytokines and induced nuclear hormone receptor signaling, both of which are common in the wound repair process. Interestingly, EE provoked tumor wound repair resolution through revascularization, plasma cell recruitment and IgA secretion, replacement of glandular tumor structures with pericytes in a process reminiscent of scarring, and normalization of microbiota. These EE-dependent changes likely underlie the profound improvement in survival of colon-tumor-bearing Tcf4Het/+ ApcMin/+ males. Our studies highlight the exciting promise of EE in the design of future therapeutic strategies for colon cancer patients.

Influence of environmental enrichment on the behavior and physiology of mice infected by Trypanosoma cruzi

“…Abnormal behaviors decreased only for the infected group and only in the post-enrichment period. Similar increases in activity and decreases in inactivity have been observed in many studies of environmental enrichment 8,[38][39][40] .…”

“…However, infected mice showed only a slight increase in activity, and this could be a direct reflection of infection with T. cruzi, as this parasite increases lethargy in animals 43 . Environmental enrichment techniques are known to diminish the expression of abnormal behaviors in many animal species 8,38,[44][45][46][47] . In the present study, abnormal behaviors did not decrease significantly during enrichment treatment in infected groups, showing that the items used may not be adequate for this.…”

“…The mice in the present study used the egg boxes to hide, reducing the visibility of mice more than the other enrichment items. PVC pipes are cold, poorly ventilated items that are difficult to manipulate, and these characteristics may have induced the mice to avoid them 38 . Straw nests and egg boxes, in contrast, are well-ventilated and more easily manipulated items, permitting all individuals to use them concomitantly, and these characteristics may have been more attractive to animals.…”

Environmental enrichment and mouse models: Current perspectives

“…The mechanism for wound repair and lifespan extension in a mouse model with colon cancer has been elucidated . Mice with a Tcf4 Het/+ ‐ and Apc Min/+ ‐mediated colon tumorigenesis that were provided environmental enrichment had improved survival by eliciting a wound repair process (revascularization, plasma cell recruitment and IgA secretion, replacement of glandular tumor tissue with pericytes, and normalizing the microbiota).…”

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

“…Our study also has implications for other chronic medical conditions including cancer. Music and EE-based interventions may serve as preclinical surrogate for developing adjunct digital therapeutics for cancer patients (43,58,127), since music can lower cancer-treatment biomarker IL-6 (94,112,145) while EE and physical exercise can reduce tumor size and increase lifespan in cancer animal models (127,128,146). Other clinical opportunities to combine non-pharmacological modalities with pharmaceutical drugs and biologics include Parkinson's and Alzheimer's diseases (21), asthma (147), arthritis (148) and affective disorders (143,149).…”