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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| Format: | Article |
| Language: | English |
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BMC
2014-02-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/2051-5960-2-17 |
| _version_ | 1797272826952024064 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-07T14:35:56Z |
| format | Article |
| id | doaj.art-6ffc29574ae24c519248f66dfe289338 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-03-07T14:35:56Z |
| publishDate | 2014-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-6ffc29574ae24c519248f66dfe2893382024-03-05T20:40:32ZengBMCActa Neuropathologica Communications2051-59602014-02-01211810.1186/2051-5960-2-17Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s diseaseSonia George0Annica Rönnbäck1Gunnar K Gouras2Géraldine H Petit3Fiona Grueninger4Bengt Winblad5Caroline Graff6Patrik Brundin7Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund UniversityAlzheimer Disease Research Center, Karolinska InstitutetExperimental Dementia Research Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund UniversityNeuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund UniversityCNS Discovery and Translation Pharma Research and Exploratory Development, F. Hoffmann-La Roche AGAlzheimer Disease Research Center, Karolinska InstitutetAlzheimer Disease Research Center, Karolinska InstitutetNeuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund UniversityAbstract 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.https://doi.org/10.1186/2051-5960-2-17Amyloid-βAlzheimer’s diseaseSubiculumTransgenic APP arctic micePrion-likeIbotenic acid |
| spellingShingle | 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 Acta Neuropathologica Communications Amyloid-β Alzheimer’s disease Subiculum Transgenic APP arctic mice Prion-like Ibotenic acid |
| 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_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_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_sort | lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of alzheimer s disease |
| topic | Amyloid-β Alzheimer’s disease Subiculum Transgenic APP arctic mice Prion-like Ibotenic acid |
| url | https://doi.org/10.1186/2051-5960-2-17 |
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