A Novel Mouse Model of Alzheimer's Disease with Chronic Estrogen Deficiency Leads to Glial Cell Activation and Hypertrophy
The role of estrogens in Alzheimer's disease (AD) involving β-amyloid (Aβ) generation and plaque formation was mostly tested in ovariectomized mice with or without APP mutations. The aim of the present study was to explore the abnormalities of neural cells in a novel mouse model of AD with chro...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Journal of Aging Research |
| Online Access: | http://dx.doi.org/10.4061/2011/251517 |
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| author | Annik Prat Maik Behrendt Edwige Marcinkiewicz Sebastien Boridy Ram M. Sairam Nabil G. Seidah Dusica Maysinger |
| author_facet | Annik Prat Maik Behrendt Edwige Marcinkiewicz Sebastien Boridy Ram M. Sairam Nabil G. Seidah Dusica Maysinger |
| author_sort | Annik Prat |
| collection | DOAJ |
| description | The role of estrogens in Alzheimer's disease (AD) involving β-amyloid (Aβ) generation and plaque formation was mostly tested in ovariectomized mice with or without APP mutations. The aim of the present study was to explore the abnormalities of neural cells in a novel mouse model of AD with chronic estrogen deficiency. These chimeric mice exhibit a total FSH-R knockout (FORKO) and carry two transgenes, one expressing the β-amyloid precursor protein (APPsw, Swedish mutation) and the other expressing presenilin-1 lacking exon 9 (PS1Δ9). The most prominent changes in the cerebral cortex and hippocampus of these hypoestrogenic mice were marked hypertrophy of both cortical neurons and astrocytes and an increased number of activated microglia. There were no significant differences in the number of Aβ plaques although they appeared less compacted and larger than those in APPsw/PS1Δ9 control mice. Similar glia abnormalities were obtained in wild-type primary cortical neural cultures treated with letrozole, an aromatase inhibitor. The concordance of results from APPsw/PS1Δ9 mice with or without FSH-R deletion and those with letrozole treatment in vitro (with and without Aβ treatment) of primary cortical/hippocampal cultures suggests the usefulness of these models to explore molecular mechanisms involved in microglia and astrocyte activation in hypoestrogenic states in the central nervous system. |
| format | Article |
| id | doaj-art-a43378623d964f76973478bcad40e7e9 |
| institution | Kabale University |
| issn | 2090-2212 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Aging Research |
| spelling | doaj-art-a43378623d964f76973478bcad40e7e92025-02-03T01:33:13ZengWileyJournal of Aging Research2090-22122011-01-01201110.4061/2011/251517251517A Novel Mouse Model of Alzheimer's Disease with Chronic Estrogen Deficiency Leads to Glial Cell Activation and HypertrophyAnnik Prat0Maik Behrendt1Edwige Marcinkiewicz2Sebastien Boridy3Ram M. Sairam4Nabil G. Seidah5Dusica Maysinger6Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, H2W 1R7, CanadaDepartment of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Room 1314, McIntyre Medical Sciences Building, Montreal, QC, H3G 1Y6, CanadaLaboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, H2W 1R7, CanadaDepartment of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Room 1314, McIntyre Medical Sciences Building, Montreal, QC, H3G 1Y6, CanadaMolecular Endocrinology Laboratory, Clinical Research Institute of Montreal, QC, CanadaLaboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, H2W 1R7, CanadaDepartment of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Room 1314, McIntyre Medical Sciences Building, Montreal, QC, H3G 1Y6, CanadaThe role of estrogens in Alzheimer's disease (AD) involving β-amyloid (Aβ) generation and plaque formation was mostly tested in ovariectomized mice with or without APP mutations. The aim of the present study was to explore the abnormalities of neural cells in a novel mouse model of AD with chronic estrogen deficiency. These chimeric mice exhibit a total FSH-R knockout (FORKO) and carry two transgenes, one expressing the β-amyloid precursor protein (APPsw, Swedish mutation) and the other expressing presenilin-1 lacking exon 9 (PS1Δ9). The most prominent changes in the cerebral cortex and hippocampus of these hypoestrogenic mice were marked hypertrophy of both cortical neurons and astrocytes and an increased number of activated microglia. There were no significant differences in the number of Aβ plaques although they appeared less compacted and larger than those in APPsw/PS1Δ9 control mice. Similar glia abnormalities were obtained in wild-type primary cortical neural cultures treated with letrozole, an aromatase inhibitor. The concordance of results from APPsw/PS1Δ9 mice with or without FSH-R deletion and those with letrozole treatment in vitro (with and without Aβ treatment) of primary cortical/hippocampal cultures suggests the usefulness of these models to explore molecular mechanisms involved in microglia and astrocyte activation in hypoestrogenic states in the central nervous system.http://dx.doi.org/10.4061/2011/251517 |
| spellingShingle | Annik Prat Maik Behrendt Edwige Marcinkiewicz Sebastien Boridy Ram M. Sairam Nabil G. Seidah Dusica Maysinger A Novel Mouse Model of Alzheimer's Disease with Chronic Estrogen Deficiency Leads to Glial Cell Activation and Hypertrophy Journal of Aging Research |
| title | A Novel Mouse Model of Alzheimer's Disease with Chronic Estrogen Deficiency Leads to Glial Cell Activation and Hypertrophy |
| title_full | A Novel Mouse Model of Alzheimer's Disease with Chronic Estrogen Deficiency Leads to Glial Cell Activation and Hypertrophy |
| title_fullStr | A Novel Mouse Model of Alzheimer's Disease with Chronic Estrogen Deficiency Leads to Glial Cell Activation and Hypertrophy |
| title_full_unstemmed | A Novel Mouse Model of Alzheimer's Disease with Chronic Estrogen Deficiency Leads to Glial Cell Activation and Hypertrophy |
| title_short | A Novel Mouse Model of Alzheimer's Disease with Chronic Estrogen Deficiency Leads to Glial Cell Activation and Hypertrophy |
| title_sort | novel mouse model of alzheimer s disease with chronic estrogen deficiency leads to glial cell activation and hypertrophy |
| url | http://dx.doi.org/10.4061/2011/251517 |
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