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The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer’s disease

Based on previous evidence that the non-steroidal estrogen receptor modulator STX mitigates the effects of neurotoxic Amyloid-β (Aβ) in vitro, we have evaluated its neuroprotective benefits in a mouse model of Alzheimer’s disease. Cohorts of 5XFAD mice, which begin to accumulate cerebral Aβ at two m...

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Autores principales: Quinn, Joseph F., Kelly, Martin J., Harris, Christopher J., Hack, Wyatt, Gray, Nora E., Kulik, Veronika, Bostick, Zoe, Brumbach, Barbara H., Copenhaver, Philip F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108899/
https://www.ncbi.nlm.nih.gov/pubmed/36209948
http://dx.doi.org/10.1016/j.nbd.2022.105888
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author Quinn, Joseph F.
Kelly, Martin J.
Harris, Christopher J.
Hack, Wyatt
Gray, Nora E.
Kulik, Veronika
Bostick, Zoe
Brumbach, Barbara H.
Copenhaver, Philip F.
author_facet Quinn, Joseph F.
Kelly, Martin J.
Harris, Christopher J.
Hack, Wyatt
Gray, Nora E.
Kulik, Veronika
Bostick, Zoe
Brumbach, Barbara H.
Copenhaver, Philip F.
author_sort Quinn, Joseph F.
collection PubMed
description Based on previous evidence that the non-steroidal estrogen receptor modulator STX mitigates the effects of neurotoxic Amyloid-β (Aβ) in vitro, we have evaluated its neuroprotective benefits in a mouse model of Alzheimer’s disease. Cohorts of 5XFAD mice, which begin to accumulate cerebral Aβ at two months of age, were treated with orally-administered STX starting at 6 months of age for two months. After behavioral testing to evaluate cognitive function, biochemical and immunohistochemical assays were used to analyze key markers of mitochondrial function and synaptic integrity. Oral STX treatment attenuated Aβ-associated mitochondrial toxicity and synaptic toxicity in the brain, as previously documented in cultured neurons. STX also moderately improved spatial memory in 5XFAD mice. In addition, STX reduced markers for reactive astrocytosis and microgliosis surrounding amyloid plaques, and also unexpectedly reduced overall levels of cerebral Aβ in the brain. The neuroprotective effects of STX were more robust in females than in males. These results suggest that STX may have therapeutic potential in Alzheimer’s Disease.
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spelling pubmed-101088992023-04-17 The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer’s disease Quinn, Joseph F. Kelly, Martin J. Harris, Christopher J. Hack, Wyatt Gray, Nora E. Kulik, Veronika Bostick, Zoe Brumbach, Barbara H. Copenhaver, Philip F. Neurobiol Dis Article Based on previous evidence that the non-steroidal estrogen receptor modulator STX mitigates the effects of neurotoxic Amyloid-β (Aβ) in vitro, we have evaluated its neuroprotective benefits in a mouse model of Alzheimer’s disease. Cohorts of 5XFAD mice, which begin to accumulate cerebral Aβ at two months of age, were treated with orally-administered STX starting at 6 months of age for two months. After behavioral testing to evaluate cognitive function, biochemical and immunohistochemical assays were used to analyze key markers of mitochondrial function and synaptic integrity. Oral STX treatment attenuated Aβ-associated mitochondrial toxicity and synaptic toxicity in the brain, as previously documented in cultured neurons. STX also moderately improved spatial memory in 5XFAD mice. In addition, STX reduced markers for reactive astrocytosis and microgliosis surrounding amyloid plaques, and also unexpectedly reduced overall levels of cerebral Aβ in the brain. The neuroprotective effects of STX were more robust in females than in males. These results suggest that STX may have therapeutic potential in Alzheimer’s Disease. 2022-11 2022-10-06 /pmc/articles/PMC10108899/ /pubmed/36209948 http://dx.doi.org/10.1016/j.nbd.2022.105888 Text en https://creativecommons.org/licenses/by/4.0/The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Quinn, Joseph F.
Kelly, Martin J.
Harris, Christopher J.
Hack, Wyatt
Gray, Nora E.
Kulik, Veronika
Bostick, Zoe
Brumbach, Barbara H.
Copenhaver, Philip F.
The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer’s disease
title The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer’s disease
title_full The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer’s disease
title_fullStr The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer’s disease
title_full_unstemmed The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer’s disease
title_short The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer’s disease
title_sort novel estrogen receptor modulator stx attenuates amyloid-β neurotoxicity in the 5xfad mouse model of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108899/
https://www.ncbi.nlm.nih.gov/pubmed/36209948
http://dx.doi.org/10.1016/j.nbd.2022.105888
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