Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice

<div><p>Accumulation of amyloid-β plaques and tau contribute to the pathogenesis of Alzheimer’s disease (AD), but it is unclear whether targeting tau pathology by antioxidants independently of amyloid-β causes beneficial effects on memory and neuropsychiatric symptoms. Selenium, an essen...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Ann Van der Jeugd (18629695) (author)
مؤلفون آخرون: Arnaldo Parra-Damas (230723) (author), Raquel Baeta-Corral (18629698) (author), Carlos M. Soto-Faguás (18629701) (author), Tariq Ahmed (5768081) (author), Frank M. LaFerla (11991116) (author), Lydia Giménez-Llort (447668) (author), Rudi D’Hooge (412153) (author), Carlos A. Saura (11666536) (author)
منشور في: 2018
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author Ann Van der Jeugd (18629695)
author2 Arnaldo Parra-Damas (230723)
Raquel Baeta-Corral (18629698)
Carlos M. Soto-Faguás (18629701)
Tariq Ahmed (5768081)
Frank M. LaFerla (11991116)
Lydia Giménez-Llort (447668)
Rudi D’Hooge (412153)
Carlos A. Saura (11666536)
author2_role author
author
author
author
author
author
author
author
author_facet Ann Van der Jeugd (18629695)
Arnaldo Parra-Damas (230723)
Raquel Baeta-Corral (18629698)
Carlos M. Soto-Faguás (18629701)
Tariq Ahmed (5768081)
Frank M. LaFerla (11991116)
Lydia Giménez-Llort (447668)
Rudi D’Hooge (412153)
Carlos A. Saura (11666536)
author_role author
dc.creator.none.fl_str_mv Ann Van der Jeugd (18629695)
Arnaldo Parra-Damas (230723)
Raquel Baeta-Corral (18629698)
Carlos M. Soto-Faguás (18629701)
Tariq Ahmed (5768081)
Frank M. LaFerla (11991116)
Lydia Giménez-Llort (447668)
Rudi D’Hooge (412153)
Carlos A. Saura (11666536)
dc.date.none.fl_str_mv 2018-04-24T03:00:00Z
dc.identifier.none.fl_str_mv 10.1038/s41598-018-24741-0
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Reversal_of_memory_and_neuropsychiatric_symptoms_and_reduced_tau_pathology_by_selenium_in_3xTg-AD_mice/25921051
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Neurosciences
Alzheimer's disease (AD)
Amyloid-β plaques
Tau pathology
Neuropathology
Selenium
Antioxidants
dc.title.none.fl_str_mv Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>Accumulation of amyloid-β plaques and tau contribute to the pathogenesis of Alzheimer’s disease (AD), but it is unclear whether targeting tau pathology by antioxidants independently of amyloid-β causes beneficial effects on memory and neuropsychiatric symptoms. Selenium, an essential antioxidant element reduced in the aging brain, prevents development of neuropathology in AD transgenic mice at early disease stages. The therapeutic potential of selenium for ameliorating or reversing neuropsychiatric and cognitive behavioral symptoms at late AD stages is largely unknown. Here, we evaluated the effects of chronic dietary sodium selenate supplementation for 4 months in female 3xTg-AD mice at 12–14 months of age. Chronic sodium selenate treatment efficiently reversed hippocampal-dependent learning and memory impairments, and behavior- and neuropsychiatric-like symptoms in old female 3xTg-AD mice. Selenium significantly decreased the number of aggregated tau-positive neurons and astrogliosis, without globally affecting amyloid plaques, in the hippocampus of 3xTg-AD mice. These results indicate that selenium treatment reverses AD-like memory and neuropsychiatric symptoms by a mechanism involving reduction of aggregated tau and/or reactive astrocytes but not amyloid pathology. These results suggest that sodium selenate could be part of a combined therapeutic approach for the treatment of memory and neuropsychiatric symptoms in advanced AD stages.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-018-24741-0" target="_blank">https://dx.doi.org/10.1038/s41598-018-24741-0</a></p>
eu_rights_str_mv openAccess
id Manara2_aa7f1ef3da3f84c115a30a982e6776a5
identifier_str_mv 10.1038/s41598-018-24741-0
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25921051
publishDate 2018
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rights_invalid_str_mv CC BY 4.0
spelling Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD miceAnn Van der Jeugd (18629695)Arnaldo Parra-Damas (230723)Raquel Baeta-Corral (18629698)Carlos M. Soto-Faguás (18629701)Tariq Ahmed (5768081)Frank M. LaFerla (11991116)Lydia Giménez-Llort (447668)Rudi D’Hooge (412153)Carlos A. Saura (11666536)Biomedical and clinical sciencesNeurosciencesAlzheimer's disease (AD)Amyloid-β plaquesTau pathologyNeuropathologySeleniumAntioxidants<div><p>Accumulation of amyloid-β plaques and tau contribute to the pathogenesis of Alzheimer’s disease (AD), but it is unclear whether targeting tau pathology by antioxidants independently of amyloid-β causes beneficial effects on memory and neuropsychiatric symptoms. Selenium, an essential antioxidant element reduced in the aging brain, prevents development of neuropathology in AD transgenic mice at early disease stages. The therapeutic potential of selenium for ameliorating or reversing neuropsychiatric and cognitive behavioral symptoms at late AD stages is largely unknown. Here, we evaluated the effects of chronic dietary sodium selenate supplementation for 4 months in female 3xTg-AD mice at 12–14 months of age. Chronic sodium selenate treatment efficiently reversed hippocampal-dependent learning and memory impairments, and behavior- and neuropsychiatric-like symptoms in old female 3xTg-AD mice. Selenium significantly decreased the number of aggregated tau-positive neurons and astrogliosis, without globally affecting amyloid plaques, in the hippocampus of 3xTg-AD mice. These results indicate that selenium treatment reverses AD-like memory and neuropsychiatric symptoms by a mechanism involving reduction of aggregated tau and/or reactive astrocytes but not amyloid pathology. These results suggest that sodium selenate could be part of a combined therapeutic approach for the treatment of memory and neuropsychiatric symptoms in advanced AD stages.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-018-24741-0" target="_blank">https://dx.doi.org/10.1038/s41598-018-24741-0</a></p>2018-04-24T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-018-24741-0https://figshare.com/articles/journal_contribution/Reversal_of_memory_and_neuropsychiatric_symptoms_and_reduced_tau_pathology_by_selenium_in_3xTg-AD_mice/25921051CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259210512018-04-24T03:00:00Z
spellingShingle Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
Ann Van der Jeugd (18629695)
Biomedical and clinical sciences
Neurosciences
Alzheimer's disease (AD)
Amyloid-β plaques
Tau pathology
Neuropathology
Selenium
Antioxidants
status_str publishedVersion
title Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
title_full Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
title_fullStr Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
title_full_unstemmed Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
title_short Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
title_sort Reversal of memory and neuropsychiatric symptoms and reduced tau pathology by selenium in 3xTg-AD mice
topic Biomedical and clinical sciences
Neurosciences
Alzheimer's disease (AD)
Amyloid-β plaques
Tau pathology
Neuropathology
Selenium
Antioxidants