Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology
Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARγ) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated...
| Main Authors: | , , , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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NATURE PUBLISHING GROUP
2010
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| Online Access: | https://hdl.handle.net/10171/12953 |
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| author | Escribano, L. (Luis) Simon, A.M. (Ana María) Gimeno, E. (Esther) Cuadrado-Tejedor, M. (Mar) Raquel Garcia-Osta, A. (Ana) Ricobaraza, A. (Ana) Perez-Mediavilla, L.A. (Luis Alberto) Rio, J. (Joaquín) del Frechilla, D. (Diana) |
| author_facet | Escribano, L. (Luis) Simon, A.M. (Ana María) Gimeno, E. (Esther) Cuadrado-Tejedor, M. (Mar) Raquel Garcia-Osta, A. (Ana) Ricobaraza, A. (Ana) Perez-Mediavilla, L.A. (Luis Alberto) Rio, J. (Joaquín) del Frechilla, D. (Diana) |
| author_sort | Escribano, L. (Luis) |
| collection | DSpace |
| description | Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARγ) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated. Here, in mice overexpressing mutant human amyloid precursor protein, we found that chronic treatment with rosiglitazone, a high-affinity agonist at PPARγ, facilitated β-amyloid peptide (Aβ) clearance. Rosiglitazone not only reduced Aβ burden in the brain but, importantly, almost completely removed the abundant amyloid plaques observed in the hippocampus and entorhinal cortex of 13-month-old transgenic mice. In the hippocampus, neuropil threads containing phosphorylated tau, probably corresponding to dystrophic neurites, were also decreased by the drug. Rosiglitazone switched on the activated microglial phenotype, promoting its phagocytic ability, reducing the expression of proinflammatory markers and inducing factors for alternative differentiation. The decreased amyloid pathology may account for the reduction of p-tau-containing neuropil threads and for the rescue of impaired recognition and spatial memory in the transgenic mice. This study provides further insights into the mechanisms for the beneficial effect of rosiglitazone in AD patients. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-12953 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2010 |
| publisher | NATURE PUBLISHING GROUP |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-129532022-11-28T11:34:04Z Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology Escribano, L. (Luis) Simon, A.M. (Ana María) Gimeno, E. (Esther) Cuadrado-Tejedor, M. (Mar) Raquel Garcia-Osta, A. (Ana) Ricobaraza, A. (Ana) Perez-Mediavilla, L.A. (Luis Alberto) Rio, J. (Joaquín) del Frechilla, D. (Diana) Alzheimer's disease amyloid; tau amyloid; tau PPARγ hippocampus memory Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARγ) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated. Here, in mice overexpressing mutant human amyloid precursor protein, we found that chronic treatment with rosiglitazone, a high-affinity agonist at PPARγ, facilitated β-amyloid peptide (Aβ) clearance. Rosiglitazone not only reduced Aβ burden in the brain but, importantly, almost completely removed the abundant amyloid plaques observed in the hippocampus and entorhinal cortex of 13-month-old transgenic mice. In the hippocampus, neuropil threads containing phosphorylated tau, probably corresponding to dystrophic neurites, were also decreased by the drug. Rosiglitazone switched on the activated microglial phenotype, promoting its phagocytic ability, reducing the expression of proinflammatory markers and inducing factors for alternative differentiation. The decreased amyloid pathology may account for the reduction of p-tau-containing neuropil threads and for the rescue of impaired recognition and spatial memory in the transgenic mice. This study provides further insights into the mechanisms for the beneficial effect of rosiglitazone in AD patients. 2010-09-23T14:57:00Z 2010-09-23T14:57:00Z 2010-03 info:eu-repo/semantics/article https://hdl.handle.net/10171/12953 eng http://www.nature.com/npp/journal/v35/n7/abs/npp201032a.html info:eu-repo/semantics/openAccess application/pdf NATURE PUBLISHING GROUP |
| spellingShingle | Alzheimer's disease amyloid; tau amyloid; tau PPARγ hippocampus memory Escribano, L. (Luis) Simon, A.M. (Ana María) Gimeno, E. (Esther) Cuadrado-Tejedor, M. (Mar) Raquel Garcia-Osta, A. (Ana) Ricobaraza, A. (Ana) Perez-Mediavilla, L.A. (Luis Alberto) Rio, J. (Joaquín) del Frechilla, D. (Diana) Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology |
| title | Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology |
| title_full | Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology |
| title_fullStr | Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology |
| title_full_unstemmed | Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology |
| title_short | Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology |
| title_sort | rosiglitazone rescues memory impairment in alzheimer's transgenic mice: mechanisms involving a reduced amyloid and tau pathology |
| topic | Alzheimer's disease amyloid; tau amyloid; tau PPARγ hippocampus memory |
| url | https://hdl.handle.net/10171/12953 |
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