title: Three-dimensional morphometric analysis of microglial changes in a mouse model of virus encephalitis: age and environmental influences.
abstract: Many RNA virus CNS infections cause neurological disease. Because Piry virus has a limited human pathogenicity and exercise reduces activation of microglia in aged mice, possible influences of environment and aging on microglial morphology and behavior in mice sublethal encephalitis were investigated. Female albino Swiss mice were raised either in standard (S) or in enriched (EE) cages from age 2 to 6 months (young - Y), or from 2 to 16 months (aged - A). After behavioral tests, mice nostrils were instilled with Piry-virus-infected or with normal brain homogenates. Brain sections were immunolabeled for virus antigens or microglia at 8 days post-infection (dpi), when behavioral changes became apparent, and at 20 and 40 dpi, after additional behavioral testing. Young infected mice from standard (SYPy) and enriched (EYPy) groups showed similar transient impairment in burrowing activity and olfactory discrimination, whereas aged infected mice from both environments (EAPy, SAPy) showed permanent reduction in both tasks. The beneficial effects of an enriched environment were smaller in aged than in young mice. Six-hundred and forty microglial cells, 80 from each group were reconstructed. An unbiased, stereological sampling approach and multivariate statistical analysis were used to search for microglial morphological families. This procedure allowed distinguishing between microglial morphology of infected and control subjects. More severe virus-associated microglial changes were observed in young than in aged mice, and EYPy seem to recover microglial homeostatic morphology earlier than SYPy . Because Piry-virus encephalitis outcomes were more severe in aged mice, it is suggested that the reduced inflammatory response in those individuals may aggravate encephalitis outcomes.
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.
authors.forename: Aline A
authors.initials: AA
authors.lastname: de Sousa
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.
authors.forename: Renata R
authors.initials: RR
authors.lastname: Dos Reis
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.
authors.forename: Camila M
authors.initials: CM
authors.lastname: de Lima
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: de Oliveira
authors.affiliation: Avenida Alcindo Cancela, Universidade da Amazônia, Belém, Pará, Brazil.
authors.forename: Taiany N
authors.initials: TN
authors.lastname: Fernandes
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.
authors.forename: Giovanni F
authors.initials: GF
authors.lastname: Gomes
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Diniz
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.
authors.forename: Nara M
authors.initials: NM
authors.lastname: Magalhães
authors.affiliation: Instituto Federal de Educação, Ciência e Tecnologia do Pará, Bragança, Pará, Brazil.
authors.forename: Cristovam G
authors.initials: CG
authors.lastname: Diniz
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.
authors.forename: Marcia C K
authors.initials: MC
authors.lastname: Sosthenes
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Bento-Torres
authors.affiliation: Instituto Evandro Chagas (IEC), Departamento de Arbovirologia e Febres Hemorrágicas, Ananindeua, Pará, Brazil.
authors.forename: José Antonio P
authors.initials: JA
authors.lastname: Diniz
authors.affiliation: Instituto Evandro Chagas (IEC), Departamento de Arbovirologia e Febres Hemorrágicas, Ananindeua, Pará, Brazil.
authors.forename: Pedro F da C
authors.initials: PF
authors.lastname: Vasconcelos
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Laboratório de Investigações em Neurodegeneração e Infecção no Hospital Universitário João de Barros Barreto, Belém, Pará, Brazil.|Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK.
authors.forename: Cristovam Wanderley P
authors.initials: CW
authors.lastname: Diniz
mesh_terms: D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology*; D017252:CD3 Complex / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D004777:Environment; D005106:Exploratory Behavior; D005260:Female; D021621:Imaging, Three-Dimensional; D008568:Memory / Q000502:physiology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000473:pathology*; D012209:Rhabdoviridae / Q000472:pathogenicity; D012903:Smell / Q000502:physiology; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D017252:CD3 Complex; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins
keywords: aging; behavioral changes; enriched environment; microglial morphometry; sublethal arbovirus encephalitis