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Early-onset dysfunction of retrosplenial cortex precedes overt amyloid plaque formation in Tg2576 mice

Poirier, Guillaume L., Amin, Eman, Good, Mark Andrew ORCID: and Aggleton, John Patrick ORCID: 2011. Early-onset dysfunction of retrosplenial cortex precedes overt amyloid plaque formation in Tg2576 mice. Neuroscience 174 , pp. 71-83. 10.1016/j.neuroscience.2010.11.025

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Alzheimer's disease; posterior cingulate cortex; diaschisis; disconnection; connectivity; energy metabolism
Publisher: Elsevier
ISSN: 0306-4522
Last Modified: 18 Oct 2022 12:49

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