Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice.
Research on Alzheimer's disease (AD) has indicated an association between hormones of the hypothalamic-pituitary-gonadal (HPG) axis and cognitive senescence, indicating that post meno-/andropausal changes in HPG axis hormones are implicated in the neuropathology of AD. Studies of transgenic mic...
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ftdoajarticles:oai:doaj.org/article:b462630ad3a74734ba68abc828da7dd3 2023-05-15T15:16:44+02:00 Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice. Syed Nuruddin Gry Helen Enger Syverstad Sveinung Lillehaug Trygve B Leergaard Lars N G Nilsson Erik Ropstad Anette Krogenæs Ira Ronit Hebold Haraldsen Reidun Torp 2014-01-01T00:00:00Z https://doi.org/10.1371/journal.pone.0103607 https://doaj.org/article/b462630ad3a74734ba68abc828da7dd3 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4121068?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0103607 https://doaj.org/article/b462630ad3a74734ba68abc828da7dd3 PLoS ONE, Vol 9, Iss 8, p e103607 (2014) Medicine R Science Q article 2014 ftdoajarticles https://doi.org/10.1371/journal.pone.0103607 2022-12-31T02:23:15Z Research on Alzheimer's disease (AD) has indicated an association between hormones of the hypothalamic-pituitary-gonadal (HPG) axis and cognitive senescence, indicating that post meno-/andropausal changes in HPG axis hormones are implicated in the neuropathology of AD. Studies of transgenic mice with AD pathologies have led to improved understanding of the pathophysiological processes underlying AD. The aims of this study were to explore whether mRNA-levels of gonadotropin-releasing hormone (Gnrh) and its receptor (Gnrhr) were changed in plaque-bearing Alzheimer's disease transgenic mice and to investigate whether these levels and amyloid plaque deposition were downregulated by treatment with a gonadotropin-releasing hormone analog (Gnrh-a; Leuprorelin acetate). The study was performed on mice carrying the Arctic and Swedish amyloid-β precursor protein (AβPP) mutations (tgArcSwe). At 12 months of age, female tgArcSwe mice showed a twofold higher level of Gnrh mRNA and more than 1.5 higher level of Gnrhr mRNA than age matched controls. Male tgArcSwe mice showed the same pattern of changes, albeit more pronounced. In both sexes, Gnrh-a treatment caused significant down-regulation of Gnrh and Gnrhr mRNA expression. Immunohistochemistry combined with quantitative image analysis revealed no significant changes in the plaque load after Gnrh-a treatment in hippocampus and thalamus. However, plaque load in the cerebral cortex of treated females tended to be lower than in female vehicle-treated mice. The present study points to the involvement of hormonal changes in AD mice models and demonstrates that these changes can be effectively counteracted by pharmacological treatment. Although known to increase in normal aging, our study shows that Gnrh/Gnrhr mRNA expression increases much more dramatically in tgArcSwe mice. Treatment with Leuprorelin acetate successfully abolished the transgene specific effects on Gnrh/Gnrhr mRNA expression. The present experimental approach should serve as a platform for further studies on the ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS ONE 9 8 e103607 |
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Medicine R Science Q Syed Nuruddin Gry Helen Enger Syverstad Sveinung Lillehaug Trygve B Leergaard Lars N G Nilsson Erik Ropstad Anette Krogenæs Ira Ronit Hebold Haraldsen Reidun Torp Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice. |
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Medicine R Science Q |
description |
Research on Alzheimer's disease (AD) has indicated an association between hormones of the hypothalamic-pituitary-gonadal (HPG) axis and cognitive senescence, indicating that post meno-/andropausal changes in HPG axis hormones are implicated in the neuropathology of AD. Studies of transgenic mice with AD pathologies have led to improved understanding of the pathophysiological processes underlying AD. The aims of this study were to explore whether mRNA-levels of gonadotropin-releasing hormone (Gnrh) and its receptor (Gnrhr) were changed in plaque-bearing Alzheimer's disease transgenic mice and to investigate whether these levels and amyloid plaque deposition were downregulated by treatment with a gonadotropin-releasing hormone analog (Gnrh-a; Leuprorelin acetate). The study was performed on mice carrying the Arctic and Swedish amyloid-β precursor protein (AβPP) mutations (tgArcSwe). At 12 months of age, female tgArcSwe mice showed a twofold higher level of Gnrh mRNA and more than 1.5 higher level of Gnrhr mRNA than age matched controls. Male tgArcSwe mice showed the same pattern of changes, albeit more pronounced. In both sexes, Gnrh-a treatment caused significant down-regulation of Gnrh and Gnrhr mRNA expression. Immunohistochemistry combined with quantitative image analysis revealed no significant changes in the plaque load after Gnrh-a treatment in hippocampus and thalamus. However, plaque load in the cerebral cortex of treated females tended to be lower than in female vehicle-treated mice. The present study points to the involvement of hormonal changes in AD mice models and demonstrates that these changes can be effectively counteracted by pharmacological treatment. Although known to increase in normal aging, our study shows that Gnrh/Gnrhr mRNA expression increases much more dramatically in tgArcSwe mice. Treatment with Leuprorelin acetate successfully abolished the transgene specific effects on Gnrh/Gnrhr mRNA expression. The present experimental approach should serve as a platform for further studies on the ... |
format |
Article in Journal/Newspaper |
author |
Syed Nuruddin Gry Helen Enger Syverstad Sveinung Lillehaug Trygve B Leergaard Lars N G Nilsson Erik Ropstad Anette Krogenæs Ira Ronit Hebold Haraldsen Reidun Torp |
author_facet |
Syed Nuruddin Gry Helen Enger Syverstad Sveinung Lillehaug Trygve B Leergaard Lars N G Nilsson Erik Ropstad Anette Krogenæs Ira Ronit Hebold Haraldsen Reidun Torp |
author_sort |
Syed Nuruddin |
title |
Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice. |
title_short |
Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice. |
title_full |
Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice. |
title_fullStr |
Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice. |
title_full_unstemmed |
Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice. |
title_sort |
elevated mrna-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing alzheimer's disease transgenic mice. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pone.0103607 https://doaj.org/article/b462630ad3a74734ba68abc828da7dd3 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS ONE, Vol 9, Iss 8, p e103607 (2014) |
op_relation |
http://europepmc.org/articles/PMC4121068?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0103607 https://doaj.org/article/b462630ad3a74734ba68abc828da7dd3 |
op_doi |
https://doi.org/10.1371/journal.pone.0103607 |
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PLoS ONE |
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9 |
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8 |
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e103607 |
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