title: Age and Environment Influences on Mouse Prion Disease Progression: Behavioral Changes and Morphometry and Stereology of Hippocampal Astrocytes.
abstract: Because enriched environment (EE) and exercise increase and aging decreases immune response, we hypothesized that environmental enrichment and aging will, respectively, delay and increase prion disease progression. Mice dorsal striatum received bilateral stereotaxic intracerebral injections of normal or ME7 prion infected mouse brain homogenates. After behavior analysis, animals were euthanized and their brains processed for astrocyte GFAP immunolabeling. Our analysis related to the environmental influence are limited to young adult mice, whereas age influence refers to aged mice raised on standard cages. Burrowing activity began to reduce in ME7-SE two weeks before ME7-EE, while no changes were apparent in ME7 aged mice (ME7-A). Object placement recognition was impaired in ME7-SE, NBH-A, and ME7-A but normal in all other groups. Object identity recognition was impaired in ME7-A. Cluster analysis revealed two morphological families of astrocytes in NBH-SE animals, three in NBH-A and ME7-A, and four in NBH-EE, ME7-SE, and ME7-EE. As compared with control groups, astrocytes from DG and CA3 prion-diseased animals show significant numerical and morphological differences and environmental enrichment did not reverse these changes but induced different morphological changes in GFAP+ hippocampal astroglia. We suggest that environmental enrichment and aging delayed hippocampal-dependent behavioral and neuropathological signs of disease progression.
authors.affiliation: Laboratório de Investigações em Neurodegeneração e Infecção, Hospital Universitário, João de Barros Barreto, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Bento-Torres
authors.affiliation: Universidade do Estado do Pará, Centro de Ciências da Saúde, Belém, PA, Brazil.
authors.forename: L L
authors.initials: LL
authors.lastname: Sobral
authors.affiliation: Vertebrate Embryology Laboratory, Biomedical Sciences Institute, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: R R
authors.identifier: 0000-0001-5877-8710
authors.initials: RR
authors.lastname: Reis
authors.affiliation: Laboratório de Investigações em Neurodegeneração e Infecção, Hospital Universitário, João de Barros Barreto, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: R B
authors.initials: RB
authors.lastname: de Oliveira
authors.affiliation: Lab of Experimental Neuropathology, Department of Pharmacology, University of Oxford, Oxford, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Anthony
authors.affiliation: Departamento de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua, PA, Brazil.
authors.forename: P F C
authors.initials: PF
authors.lastname: Vasconcelos
authors.affiliation: Laboratório de Investigações em Neurodegeneração e Infecção, Hospital Universitário, João de Barros Barreto, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Cristovam Wanderley
authors.identifier: 0000-0001-6611-6880
authors.initials: CW
authors.lastname: Picanço Diniz
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004777:Environment; D006624:Hippocampus / Q000473:pathology*; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D017096:Prion Diseases / Q000473:pathology* / Q000523:psychology*