Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects
Abstract 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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/trc2.12231 |
| _version_ | 1828134571452923904 |
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| author | Tamunotonye Omoluabi Sarah E. Torraville Aida Maziar Abhinaba Ghosh Kyron D. Power Camila Reinhardt Carolyn W. Harley Qi Yuan |
| author_facet | Tamunotonye Omoluabi Sarah E. Torraville Aida Maziar Abhinaba Ghosh Kyron D. Power Camila Reinhardt Carolyn W. Harley Qi Yuan |
| author_sort | Tamunotonye Omoluabi |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T17:36:26Z |
| format | Article |
| id | doaj.art-49a7285d9c4d4f9caabc08408d2cf606 |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2024-04-11T17:36:26Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-49a7285d9c4d4f9caabc08408d2cf6062022-12-22T04:11:35ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372021-01-0171n/an/a10.1002/trc2.12231Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effectsTamunotonye Omoluabi0Sarah E. Torraville1Aida Maziar2Abhinaba Ghosh3Kyron D. Power4Camila Reinhardt5Carolyn W. Harley6Qi Yuan7Division of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador CanadaDivision of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador CanadaDivision of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador CanadaDivision of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador CanadaDivision of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador CanadaDivision of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador CanadaDepartment of Psychology, Faculty of Science Memorial University St. John's Newfoundland and Labrador CanadaDivision of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador CanadaAbstract 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.https://doi.org/10.1002/trc2.12231locus coeruleusolfactory discriminationoptogenetic stimulationpretangle tauspatial discrimination |
| spellingShingle | Tamunotonye Omoluabi Sarah E. Torraville Aida Maziar Abhinaba Ghosh Kyron D. Power Camila Reinhardt Carolyn W. Harley Qi Yuan Novelty‐like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress‐inducing activation worsens its effects Alzheimer’s & Dementia: Translational Research & Clinical Interventions locus coeruleus olfactory discrimination optogenetic stimulation pretangle tau spatial discrimination |
| 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 | locus coeruleus olfactory discrimination optogenetic stimulation pretangle tau spatial discrimination |
| url | https://doi.org/10.1002/trc2.12231 |
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