title: Chronic Progressive Neurodegeneration in a Transgenic Mouse Model of Prion Disease.
abstract: Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic proteins without an accompanying neurodegeneration pattern. The lack of a comprehensive model hinders efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice mimicking for genetic Creutzfeldt-Jacob disease as compared to age-matched wild-type mice. Mice exhibited a neurodegenerative process of progressive reduction in cortical neurons and synapses starting at age of 4-6 months, in accord with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with neurological disease progression, indicating these mice can serve as a model for neurodegenerative diseases.
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center Jerusalem, Israel.
authors.forename: Nina
authors.initials: N
authors.lastname: Fainstein
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center Jerusalem, Israel.
authors.forename: Dvir
authors.initials: D
authors.lastname: Dori
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center Jerusalem, Israel.
authors.forename: Kati
authors.initials: K
authors.lastname: Frid
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center Jerusalem, Israel.
authors.forename: Alexa T
authors.initials: AT
authors.lastname: Fritz
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center Jerusalem, Israel.
authors.forename: Ilona
authors.initials: I
authors.lastname: Shapiro
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center Jerusalem, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gabizon
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center Jerusalem, Israel.
authors.forename: Tamir
authors.initials: T
authors.lastname: Ben-Hur
keywords: aging; animal model; neurodegeneration; neurogenesis; prion diseases