title: Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease: stereological analysis in the albino Swiss mice model.
abstract: Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration, and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression.
authors.affiliation: Laboratory of Neurodegeneration and Infection at the University Hospital João de Barros Barreto, Federal University of Pará, Belém, Pará, Brazil.
authors.forename: Roseane
authors.initials: R
authors.lastname: Borner
authors.forename: João
authors.initials: J
authors.lastname: Bento-Torres
authors.forename: Diego R V
authors.initials: DR
authors.lastname: Souza
authors.forename: Danyelle B
authors.initials: DB
authors.lastname: Sadala
authors.forename: Nonata
authors.initials: N
authors.lastname: Trevia
authors.forename: José Augusto
authors.initials: JA
authors.lastname: Farias
authors.forename: Nara
authors.initials: N
authors.lastname: Lins
authors.forename: Aline
authors.initials: A
authors.lastname: Passos
authors.forename: Amanda
authors.initials: A
authors.lastname: Quintairos
authors.forename: José Antônio
authors.initials: JA
authors.lastname: Diniz
authors.forename: Victor Hugh
authors.initials: VH
authors.lastname: Perry
authors.forename: Pedro Fernando
authors.initials: PF
authors.lastname: Vasconcelos
authors.forename: Colm
authors.initials: C
authors.lastname: Cunningham
authors.forename: Cristovam W
authors.initials: CW
authors.lastname: Picanço-Diniz
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D017096:Prion Diseases / Q000473:pathology* / Q000523:psychology*