title: Progression of motor deficits in glioma-bearing mice: impact of CNF1 therapy at symptomatic stages.
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.
authors.affiliation: Institute of Neuroscience, National Research Council (CNR), Pisa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Vannini
authors.affiliation: Institute of Neuroscience, National Research Council (CNR), Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Maltese
authors.affiliation: BioSNS laboratory, Scuola Normale Superiore di Pisa Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Olimpico
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Fabbri
authors.affiliation: Institute of Neuroscience, National Research Council (CNR), Pisa, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Costa
authors.affiliation: Institute of Neuroscience, National Research Council (CNR), Pisa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Caleo
authors.affiliation: Institute of Neuroscience, National Research Council (CNR), Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Baroncelli
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D000076122:Disks Large Homolog 4 Protein; D029968:Escherichia coli Proteins / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051528:Guanylate Kinases / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D000068079:Motor Disorders / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D001427:Bacterial Toxins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; C060296:cytotoxic necrotizing factor type 1; D051528:Guanylate Kinases
keywords: CNF1; behavioral test; glioma; motor cortex; mouse model