title: Aβ plaque-associated glial reaction as a determinant of apoptotic neuronal death and cortical gliogenesis: a study in APP mutant mice.
abstract: The purpose of this study was to investigate the microglia-driven apoptosis and the Aβ deposits triggered generation of new microglial cells in the neocortex of TgCRND8 mice. Three- and seven-month-old TgCRND8 mice, displaying an early and widespread amyloid deposition, respectively, were used. In 7-month-old TgCRND8 mice the Aβ-associated glial reaction was accompanied by an intense immunoreactivity of both TNF-α and inducible nitric oxide synthase, increased immunoreactivity of the pro-apoptotic protein Bax and a decrease in levels of the anti-apoptotic protein Bcl-2.Cortical and hippocampal neurons of TgCRND8 mice displayed higher immunoreactivity and higher nuclear expression of the transcription factor NF-kB than controls. It is possible that such an increase could represent a defence/compensatory response to degeneration. These findings indicate that Aβ deposits activate brain-resident microglia population and astrocytes, and induce overproduction of inflammatory mediators that enhance pro- and anti-apoptotic cascades. In both 3- and 7-month-old TgCRND8 mice apparent gliogenesis was present in the vicinity of Aβ plaques in the neocortex, indicating that microglia have a high proliferative rate which might play a more complex role than previously acknowledge.
authors: Department of Pharmacology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy.
authors: Ilaria
authors: I
authors: Luccarini
authors: Cristina
authors: C
authors: Grossi
authors: Chiara
authors: C
authors: Traini
authors: Anna
authors: A
authors: Fiorentini
authors: Teresa
authors: T
authors: Ed Dami
authors: Fiorella
authors: F
authors: Casamenti
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology*
chemical_list: C491049:Aif1 protein, mouse; D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D052247:Nitric Oxide Synthase Type II; D001973:Bromodeoxyuridine