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Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects
The earliest abnormality associated with Alzheimer's disease (AD) is the presence of persistently phosphorylated pretangle tau in locus coeruleus (LC) neurons. LC neuron numbers and fiber density are positive predictors of cognition prior to death. Using an animal model of LC pretangle tau, we...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719346/ https://www.ncbi.nlm.nih.gov/pubmed/35005208 http://dx.doi.org/10.1002/trc2.12231 |
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author | Omoluabi, Tamunotonye Torraville, Sarah E. Maziar, Aida Ghosh, Abhinaba Power, Kyron D. Reinhardt, Camila Harley, Carolyn W. Yuan, Qi |
author_facet | Omoluabi, Tamunotonye Torraville, Sarah E. Maziar, Aida Ghosh, Abhinaba Power, Kyron D. Reinhardt, Camila Harley, Carolyn W. Yuan, Qi |
author_sort | Omoluabi, Tamunotonye |
collection | PubMed |
description | The earliest abnormality associated with Alzheimer's disease (AD) is the presence of persistently phosphorylated pretangle tau in locus coeruleus (LC) neurons. LC neuron numbers and fiber density are positive predictors of cognition prior to death. Using an animal model of LC pretangle tau, we ask if LC activity patterns influence the sequelae of pretangle tau. We seeded LC neurons with a pretangle human tau gene. We provided daily novelty‐ or stress‐associated optogenetic activation patterns to LC neurons for 6 weeks in mid‐adulthood and, subsequently, probed cognitive and anatomical changes. Prior LC phasic stimulation prevented spatial and olfactory discrimination deficits and preserved LC axonal density. A stress‐associated activation pattern increased indices of anxiety and depression, did not improve cognition, and worsened LC neuronal health. These results argue that variations in environmental experiences associated with differing LC activity patterns may account for individual susceptibility to development of AD in humans. |
format | Online Article Text |
id | pubmed-8719346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87193462022-01-07 Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects Omoluabi, Tamunotonye Torraville, Sarah E. Maziar, Aida Ghosh, Abhinaba Power, Kyron D. Reinhardt, Camila Harley, Carolyn W. Yuan, Qi Alzheimers Dement (N Y) Alternate Format Research Article The earliest abnormality associated with Alzheimer's disease (AD) is the presence of persistently phosphorylated pretangle tau in locus coeruleus (LC) neurons. LC neuron numbers and fiber density are positive predictors of cognition prior to death. Using an animal model of LC pretangle tau, we ask if LC activity patterns influence the sequelae of pretangle tau. We seeded LC neurons with a pretangle human tau gene. We provided daily novelty‐ or stress‐associated optogenetic activation patterns to LC neurons for 6 weeks in mid‐adulthood and, subsequently, probed cognitive and anatomical changes. Prior LC phasic stimulation prevented spatial and olfactory discrimination deficits and preserved LC axonal density. A stress‐associated activation pattern increased indices of anxiety and depression, did not improve cognition, and worsened LC neuronal health. These results argue that variations in environmental experiences associated with differing LC activity patterns may account for individual susceptibility to development of AD in humans. John Wiley and Sons Inc. 2021-12-31 /pmc/articles/PMC8719346/ /pubmed/35005208 http://dx.doi.org/10.1002/trc2.12231 Text en © 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Alternate Format Research Article Omoluabi, Tamunotonye Torraville, Sarah E. Maziar, Aida Ghosh, Abhinaba Power, Kyron D. Reinhardt, Camila Harley, Carolyn W. Yuan, Qi Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects |
title | Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects |
title_full | Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects |
title_fullStr | Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects |
title_full_unstemmed | Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects |
title_short | Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects |
title_sort | novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects |
topic | Alternate Format Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719346/ https://www.ncbi.nlm.nih.gov/pubmed/35005208 http://dx.doi.org/10.1002/trc2.12231 |
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