title: Early-onset dysfunction of retrosplenial cortex precedes overt amyloid plaque formation in Tg2576 mice.
abstract: A mouse model of amyloid pathology was used to first examine using a cross sectional design changes in retrosplenial cortex activity in transgenic mice aged 5, 11, 17, and 23 months. Attention focused on: (1) overt amyloid labeled with β-amyloid((1-42)) and Congo Red staining, (2) metabolic function assessed by the enzyme, cytochrome oxidase, and (3) neuronal activity as assessed indirectly by the immediate-early gene (IEG), c-Fos. Changes in cytochrome oxidase and c-Fos activity were observed in the retrosplenial cortex in Tg2576 mice as early as 5 months of age, long before evidence of plaque formation. Subsequent analyses concentrating on this early dysfunction revealed at 5 months pervasive, amyloid precursor protein (APP)-derived peptide accumulation in the retrosplenial cortex and selective afferents (anterior thalamus, hippocampus), which was associated with the observed c-Fos hyporeactivity. These findings indicate that retrosplenial cortex dysfunction occurs during early stages of amyloid production in Tg2576 mice and may contribute to cognitive dysfunction.
authors.affiliation: School of Psychology, Cardiff University, 70 Park Place, Cardiff, Wales, CF10 3AT, UK. guillaume.poirier@epfl.ch
authors.forename: G L
authors.initials: GL
authors.lastname: Poirier
authors.forename: E
authors.initials: E
authors.lastname: Amin
authors.forename: M A
authors.initials: MA
authors.lastname: Good
authors.forename: J P
authors.initials: JP
authors.lastname: Aggleton
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism*; D018728:Entorhinal Cortex / Q000378:metabolism / Q000473:pathology; D005106:Exploratory Behavior; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism / Q000473:pathology; D014793:Visual Cortex / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; C075222:amyloid beta-protein (1-42); D003576:Electron Transport Complex IV