Oncotarget

Research Papers:

Progression of motor deficits in glioma-bearing mice: impact of CNF1 therapy at symptomatic stages

Eleonora Vannini, Federica Maltese, Francesco Olimpico, Alessia Fabbri, Mario Costa, Matteo Caleo and Laura Baroncelli _

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Oncotarget. 2017; 8:23539-23550. https://doi.org/10.18632/oncotarget.15328

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Abstract

Eleonora Vannini1,*, Federica Maltese1,*, Francesco Olimpico2,*, Alessia Fabbri3, Mario Costa1, Matteo Caleo1, Laura Baroncelli1

1Institute of Neuroscience, National Research Council (CNR), Pisa, Italy

2BioSNS laboratory, Scuola Normale Superiore di Pisa, Pisa, Italy

3Istituto Superiore di Sanità, Rome, Italy

*These authors have contributed equally to this work

Correspondence to:

Laura Baroncelli, email: baroncelli@in.cnr.it

Matteo Caleo, email: caleo@in.cnr.it

Keywords: glioma, motor cortex, behavioral test, CNF1, mouse model

Received: May 27, 2016    Accepted: January 23, 2017    Published: February 15, 2017

ABSTRACT

Glioblastoma (GBM) is the most aggressive type of brain tumor. In this context, animal models represent excellent tools for the early detection and longitudinal mapping of neuronal dysfunction, that are critical in the preclinical validation of new therapeutic strategies. In a mouse glioma model, we developed sensitive behavioral readouts that allow early recognizing and following neurological symptoms. We injected GL261 cells into the primary motor cortex of syngenic mice and we used a battery of behavioral tests to longitudinally monitor the dysfunction induced by tumor growth. Grip strength test revealed an early onset of functional deficit associated to the glioma growth, with a significant forelimb weakness appearing 9 days after tumor inoculation. A later deficit was observed in the rotarod and in the grid walk tasks. Using this model, we found reduced tumor growth and maintenance of behavioral functions following treatment with Cytotoxic Necrotizing Factor 1 (CNF1) at a symptomatic stage. Our data provide a detailed and precise examination of how tumor growth reverberates on the behavioral functions of glioma-bearing mice, providing normative data for the study of therapeutic strategies for glioma treatment. The reduced tumor volume and robust functional sparing observed in CNF1-treated, glioma-bearing mice strengthen the notion that CNF1 delivery is a promising strategy for glioma therapy.


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