Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice
Alzheimer's disease (AD) is a neurodegenerative disease hallmarked by extracellular Aβ1–42 containing plaques, and intracellular neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Progressively, memory deficits and cognitive disabilities start to occur as these hallmarks...
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| Format: | Article |
| Language: | English |
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Elsevier
2013-02-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996112003105 |
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| author | Adrian C. Lo Zsuzsanna Callaerts-Vegh Ana F. Nunes Cecília M.P. Rodrigues Rudi D'Hooge |
| author_facet | Adrian C. Lo Zsuzsanna Callaerts-Vegh Ana F. Nunes Cecília M.P. Rodrigues Rudi D'Hooge |
| author_sort | Adrian C. Lo |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is a neurodegenerative disease hallmarked by extracellular Aβ1–42 containing plaques, and intracellular neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Progressively, memory deficits and cognitive disabilities start to occur as these hallmarks affect hippocampus and frontal cortex, regions highly involved in memory. Connective tissue growth factor (CTGF) expression, which is high in the vicinity of Aβ plaques and NFTs, was found to influence γ-secretase activity, the molecular crux in Aβ1–42 production. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that downregulates CTGF expression in hepatocytes and has been shown to possess therapeutic efficacy in neurodegenerative models. To investigate the possible in vivo therapeutic effects of TUDCA, we provided 0.4% TUDCA-supplemented food to APP/PS1 mice, a well-established AD mouse model. Six months of TUDCA supplementation prevented the spatial, recognition and contextual memory defects observed in APP/PS1 mice at 8 months of age. Furthermore, TUDCA-supplemented APP/PS1 mice displayed reduced hippocampal and prefrontal amyloid deposition. These effects of TUDCA supplementation suggest a novel mechanistic route for Alzheimer therapeutics. |
| first_indexed | 2024-12-13T18:52:30Z |
| format | Article |
| id | doaj.art-ced33af434a447ab84c678b242296a58 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T18:52:30Z |
| publishDate | 2013-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-ced33af434a447ab84c678b242296a582022-12-21T23:34:55ZengElsevierNeurobiology of Disease1095-953X2013-02-01502129Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 miceAdrian C. Lo0Zsuzsanna Callaerts-Vegh1Ana F. Nunes2Cecília M.P. Rodrigues3Rudi D'Hooge4Laboratory of Biological Psychology, Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, BelgiumLaboratory of Biological Psychology, Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, BelgiumResearch Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, PortugalResearch Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Correspondence to: R. D'Hooge, Laboratory of Biological Psychology, Tiensestraat 102, B-3000 Leuven, Belgium.Laboratory of Biological Psychology, Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, Belgium; Correspondence to: C. Rodrigues, iMed.UL, Faculty of Pharmacy, University of Lisbon, Lisbon 1649‐003, Portugal.Alzheimer's disease (AD) is a neurodegenerative disease hallmarked by extracellular Aβ1–42 containing plaques, and intracellular neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Progressively, memory deficits and cognitive disabilities start to occur as these hallmarks affect hippocampus and frontal cortex, regions highly involved in memory. Connective tissue growth factor (CTGF) expression, which is high in the vicinity of Aβ plaques and NFTs, was found to influence γ-secretase activity, the molecular crux in Aβ1–42 production. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that downregulates CTGF expression in hepatocytes and has been shown to possess therapeutic efficacy in neurodegenerative models. To investigate the possible in vivo therapeutic effects of TUDCA, we provided 0.4% TUDCA-supplemented food to APP/PS1 mice, a well-established AD mouse model. Six months of TUDCA supplementation prevented the spatial, recognition and contextual memory defects observed in APP/PS1 mice at 8 months of age. Furthermore, TUDCA-supplemented APP/PS1 mice displayed reduced hippocampal and prefrontal amyloid deposition. These effects of TUDCA supplementation suggest a novel mechanistic route for Alzheimer therapeutics.http://www.sciencedirect.com/science/article/pii/S0969996112003105Alzheimer's diseaseAPP/PS1TUDCALearning and memoryMorris water maze |
| spellingShingle | Adrian C. Lo Zsuzsanna Callaerts-Vegh Ana F. Nunes Cecília M.P. Rodrigues Rudi D'Hooge Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice Neurobiology of Disease Alzheimer's disease APP/PS1 TUDCA Learning and memory Morris water maze |
| title | Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice |
| title_full | Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice |
| title_fullStr | Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice |
| title_full_unstemmed | Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice |
| title_short | Tauroursodeoxycholic acid (TUDCA) supplementation prevents cognitive impairment and amyloid deposition in APP/PS1 mice |
| title_sort | tauroursodeoxycholic acid tudca supplementation prevents cognitive impairment and amyloid deposition in app ps1 mice |
| topic | Alzheimer's disease APP/PS1 TUDCA Learning and memory Morris water maze |
| url | http://www.sciencedirect.com/science/article/pii/S0969996112003105 |
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