Voluntary Physical Exercise Reduces Motor Dysfunction and Hampers Tumor Cell Proliferation in a Mouse Model of Glioma.

Elena Tantillo,Eleonora Vannini,Matteo Caleo,Antonella Colistra,Mario Costa,Laura Baroncelli

doi:10.3390/ijerph17165667

Abstract

Currently, high-grade gliomas are the most difficult brain cancers to treat and all the approved experimental treatments do not offer long-term benefits regarding symptom improvement. Epidemiological studies indicate that exercise decreases the risk of brain cancer mortality, but a direct relationship between physical exercise and glioma progression has not been established so far. Here, we exploited a mouse model of high-grade glioma to directly test the impact of voluntary physical exercise on the tumor proliferation and motor capabilities of affected animals. We report that exposing symptomatic, glioma-bearing mice to running wheels (i) reduced the proliferation rate of tumors implanted in the motor cortex and (ii) delayed glioma-induced motor dysfunction. Thus, voluntary physical exercise might represent a supportive intervention that complements existing neuro-oncologic therapies, contributing to the preservation of functional motor ability and counteracting the detrimental effects of glioma on behavioral output.

Highlights

Voluntary physical exercise is among the components of the well-known paradigm of environmental enrichment (EE), a very effective strategy to restore plasticity and elicit recovery from different neurodevelopmental disorders [1,2,3,4,5,6,7]
Tumors were induced using a unilateral injection of syngeneic GL261 cells into the mouse motor cortex and 12 days after tumor induction, i.e., at symptomatic stages of the pathology [28], mice were randomized to either remain in standard cages or be placed into cages containing a running wheel (Figure 1A)
We found that glioma-bearing mice ran on average 1.215 km/week, comparable to km/week, comparable to naive animals reared in the same conditions (t-test, p = 0.79; Figure 1B)

Summary

Introduction

Voluntary physical exercise is among the components of the well-known paradigm of environmental enrichment (EE), a very effective strategy to restore plasticity and elicit recovery from different neurodevelopmental disorders [1,2,3,4,5,6,7]. EE consists of rearing animals in large social groups and in the presence of running wheels and many stimulating objects that are regularly changed and substituted to stimulate explorative behavior, curiosity, and attentional processes [9,10]. EE enhances plasticity in the cerebral cortex, allowing for the recovery of visual functions in amblyopic animals [6]. The molecular substrate of the effects of EE on brain plasticity is multi-factorial, with reduced intracerebral inhibition, enhanced neurotrophin expression, and epigenetic changes

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Discussion

Conclusion