title: Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice.
abstract: Mice exposed to standard (SE) or enriched environment (EE) were transplanted with murine or human glioma cells and differences in tumour development were evaluated. We report that EE exposure affects: (i) tumour size, increasing mice survival; (ii) glioma establishment, proliferation and invasion; (iii) microglia/macrophage (M/Mφ) activation; (iv) natural killer (NK) cell infiltration and activation; and (v) cerebral levels of IL-15 and BDNF. Direct infusion of IL-15 or BDNF in the brain of mice transplanted with glioma significantly reduces tumour growth. We demonstrate that brain infusion of IL-15 increases the frequency of NK cell infiltrating the tumour and that NK cell depletion reduces the efficacy of EE and IL-15 on tumour size and of EE on mice survival. BDNF infusion reduces M/Mφ infiltration and CD68 immunoreactivity in tumour mass and reduces glioma migration inhibiting the small G protein RhoA through the truncated TrkB.T1 receptor. These results suggest alternative approaches for glioma treatment.
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Garofalo
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: D'Alessandro
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Chece
authors.affiliation: Université Nice-Sophia Antipolis, IPMC CNRS-UMR, 7275 Valbonne, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Brau
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Maggi
authors.affiliation: Department of Biology and Biotechnology Charles Darwin, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rosa
authors.affiliation: Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Porzia
authors.affiliation: Department of Experimental Medicine, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mainiero
authors.affiliation: 1] IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, IS, Italy [2] Department of Neurology and Psychiatry, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Esposito
authors.affiliation: Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Lauro
authors.affiliation: Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Benigni
authors.affiliation: Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bernardini
authors.affiliation: 1] Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy [2] IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, IS, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.affiliation: 1] Department of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy [2] IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, IS, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Limatola
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004777:Environment; D005910:Glioma / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010812:Physical Stimulation; D010988:Play and Playthings; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism; D012931:Social Environment; D015996:Survival Rate; D047368:Tumor Burden / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D020742:rhoA GTP-Binding Protein; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019208:Brain-Derived Neurotrophic Factor; D019409:Interleukin-15; D020813:Receptor, trkB; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C526380:RhoA protein, mouse
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