1. Early-onset dysfunction of retrosplenial cortex precedes overt amyloid plaque formation in Tg2576 mice
- Author
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Guillaume L. Poirier, Eman Amin, Mark Andrew Good, and John Patrick Aggleton
- Subjects
Cingulate cortex ,medicine.medical_specialty ,Amyloid ,Thalamus ,Hippocampus ,Mice, Transgenic ,Plaque, Amyloid ,Gyrus Cinguli ,Article ,Electron Transport Complex IV ,Amyloid beta-Protein Precursor ,Mice ,Retrosplenial cortex ,Internal medicine ,mental disorders ,medicine ,Amyloid precursor protein ,Animals ,Entorhinal Cortex ,Visual Cortex ,Amyloid beta-Peptides ,biology ,business.industry ,General Neuroscience ,Entorhinal cortex ,medicine.disease ,Peptide Fragments ,Endocrinology ,Mutation ,Exploratory Behavior ,biology.protein ,Alzheimer's disease ,business ,Proto-Oncogene Proteins c-fos - 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.
- Published
- 2011