Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s disease
Abstract 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 connecte...
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ftdoajarticles:oai:doaj.org/article:6ffc29574ae24c519248f66dfe289338 2024-09-09T19:21:11+00:00 Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s disease Sonia George Annica Rönnbäck Gunnar K Gouras Géraldine H Petit Fiona Grueninger Bengt Winblad Caroline Graff Patrik Brundin 2014-02-01T00:00:00Z https://doi.org/10.1186/2051-5960-2-17 https://doaj.org/article/6ffc29574ae24c519248f66dfe289338 EN eng BMC https://doi.org/10.1186/2051-5960-2-17 https://doaj.org/toc/2051-5960 doi:10.1186/2051-5960-2-17 2051-5960 https://doaj.org/article/6ffc29574ae24c519248f66dfe289338 Acta Neuropathologica Communications, Vol 2, Iss 1, Pp 1-8 (2014) Amyloid-β Alzheimer’s disease Subiculum Transgenic APP arctic mice Prion-like Ibotenic acid Neurology. Diseases of the nervous system RC346-429 article 2014 ftdoajarticles https://doi.org/10.1186/2051-5960-2-17 2024-08-05T17:49:52Z Abstract 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Acta Neuropathologica Communications 2 1 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Amyloid-β Alzheimer’s disease Subiculum Transgenic APP arctic mice Prion-like Ibotenic acid Neurology. Diseases of the nervous system RC346-429 |
spellingShingle |
Amyloid-β Alzheimer’s disease Subiculum Transgenic APP arctic mice Prion-like Ibotenic acid Neurology. Diseases of the nervous system RC346-429 Sonia George Annica Rönnbäck Gunnar K Gouras Géraldine H Petit Fiona Grueninger Bengt Winblad Caroline Graff Patrik Brundin Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s disease |
topic_facet |
Amyloid-β Alzheimer’s disease Subiculum Transgenic APP arctic mice Prion-like Ibotenic acid Neurology. Diseases of the nervous system RC346-429 |
description |
Abstract 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. |
format |
Article in Journal/Newspaper |
author |
Sonia George Annica Rönnbäck Gunnar K Gouras Géraldine H Petit Fiona Grueninger Bengt Winblad Caroline Graff Patrik Brundin |
author_facet |
Sonia George Annica Rönnbäck Gunnar K Gouras Géraldine H Petit Fiona Grueninger Bengt Winblad Caroline Graff Patrik Brundin |
author_sort |
Sonia George |
title |
Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s disease |
title_short |
Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s disease |
title_full |
Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s disease |
title_fullStr |
Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s disease |
title_full_unstemmed |
Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s disease |
title_sort |
lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of alzheimer’s disease |
publisher |
BMC |
publishDate |
2014 |
url |
https://doi.org/10.1186/2051-5960-2-17 https://doaj.org/article/6ffc29574ae24c519248f66dfe289338 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Acta Neuropathologica Communications, Vol 2, Iss 1, Pp 1-8 (2014) |
op_relation |
https://doi.org/10.1186/2051-5960-2-17 https://doaj.org/toc/2051-5960 doi:10.1186/2051-5960-2-17 2051-5960 https://doaj.org/article/6ffc29574ae24c519248f66dfe289338 |
op_doi |
https://doi.org/10.1186/2051-5960-2-17 |
container_title |
Acta Neuropathologica Communications |
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2 |
container_issue |
1 |
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1809761394250219520 |