Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer's disease
| Autor: | Fiona Grueninger, Géraldine H Petit, Gunnar K. Gouras, Sonia George, Bengt Winblad, Patrik Brundin, Caroline Graff, Annica Rönnbäck |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Pathology
Subiculum Hippocampus Transgenic APP arctic mice Cell Count Functional Laterality Amyloid beta-Protein Precursor Mice 0302 clinical medicine Retrosplenial cortex Amyloid precursor protein Excitatory Amino Acid Agonists Prion-like 0303 health sciences biology Age Factors Brain Human brain medicine.anatomical_structure Alzheimer's disease Alzheimer’s disease medicine.medical_specialty Amyloid beta Mice Transgenic Pathology and Forensic Medicine 03 medical and health sciences Cellular and Molecular Neuroscience Alzheimer Disease medicine Biological neural network Animals Humans Amyloid-β 030304 developmental biology Amyloid beta-Peptides business.industry Research Neurosciences medicine.disease Ibotenic acid Disease Models Animal nervous system Gene Expression Regulation Mutation biology.protein Neurology (clinical) business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Acta Neuropathologica Communications Acta Neuropathologica Communications; 2(1), no 17 (2014) |
| ISSN: | 2051-5960 |
| Popis: | Background The progressive development of Alzheimer’s disease (AD) pathology follows a spatiotemporal pattern in the human brain. In a transgenic (Tg) mouse model of AD expressing amyloid precursor protein (APP) with the arctic (E693G) mutation, pathology spreads along anatomically connected structures. Amyloid-β (Aβ) pathology first appears in the subiculum and is later detected in interconnected brain regions, including the retrosplenial cortex. We investigated whether the spatiotemporal pattern of Aβ pathology in the Tg APP arctic mice to interconnected brain structures can be interrupted by destroying neurons using a neurotoxin and thereby disconnecting the neural circuitry. Results We performed partial unilateral ibotenic acid lesions of the subiculum (first structure affected by Aβ pathology) in young Tg APParc mice, prior to the onset of pathology. We assessed Aβ/C99 pathology in mice aged up to 6 months after injecting ibotenate into the subiculum. Compared to the brains of intact Tg APP arctic mice, we observed significantly decreased Aβ/C99 pathology in the ipsilateral dorsal subiculum, CA1 region of the hippocampus and the retrosplenial cortex; regions connecting to and from the dorsal subiculum. By contrast, Aβ/C99 pathology was unchanged in the contralateral hippocampus in the mice with lesions. Conclusion These results, obtained in an animal model of AD, support the notion that Aβ/C99 pathology is transmitted between interconnected neurons in AD. |
| Databáze: | OpenAIRE |
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