title: Pathogen-free husbandry conditions alleviate behavioral deficits and neurodegeneration in AD10 anti-NGF mice.
abstract: It has been suggested that systemic infection, occurring during aging and chronic neurodegenerative diseases, can evoke an immune response that aggravates the progression of neurodegeneration and cognitive decline. It has been shown that the AD11 neurodegeneration mouse model, expressing a recombinant anti-nerve growth factor (NGF) antibody, shows a milder phenotype when housed in murine pathogen-free (MPF) conditions with respect to AD11 mice reared in conventional (CV) housing. AD10 mice, a variant of the anti-NGF AD11 model, expressing only an immunoglobulin light chain for the transgenic anti-NGF antibody, in the absence of the corresponding transgenic antibody chain VH, exhibit a complex neurodegenerative phenotype, similar to that of AD11 mice. Here we show that the AD10 transgenic mice, housed in murine pathogen-free conditions (MPF-AD10 mice), also display a milder behavioral and neurodegenerative phenotype compared to the corresponding mice kept under conventional housing conditions (CV-AD10). As a first step toward the identification of mechanisms underlying this difference, a differential gene expression profiling was performed on brains from CV-AD10 and MPF-AD10 mice, showing a decrease of the immune response and neuroinflammation gene expression in MPF-AD10 mice. Results suggest that the activation of the immune response gene expression in the CV-AD10, in a microbially unprotected environment, might contribute to a more severe and progressive neurodegenerative phenotype, compared to the MPF mice.
authors.affiliation: Laboratory of Behavioral Genetics, School of Life Sciences, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Stamatina
authors.initials: S
authors.lastname: Tzanoulinou
authors.forename: Rossella
authors.initials: R
authors.lastname: Brandi
authors.forename: Ivan
authors.initials: I
authors.lastname: Arisi
authors.forename: Mara
authors.initials: M
authors.lastname: D'Onofrio
authors.forename: Séverine M
authors.initials: SM
authors.lastname: Urfer
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
authors.forename: Daniel
authors.initials: D
authors.lastname: Constam
authors.forename: Simona
authors.initials: S
authors.lastname: Capsoni
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control*; D000822:Animal Husbandry / Q000379:methods*; D000818:Animals; D006799:Housing, Animal; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D000090204:Mesothelin; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000235:genetics* / Q000276:immunology; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D013047:Specific Pathogen-Free Organisms / Q000235:genetics / Q000276:immunology
chemical_list: C000715528:Msln protein, mouse; D020932:Nerve Growth Factor; D000090204:Mesothelin
keywords: Memory deficits; murine pathogen-free; nerve growth factor; neuroinflammation; systemic inflammation