Novelty-like activation of locus coeruleus protects against deleterious human pretangle tau effects while stress-inducing activation worsens its effects.

Autor: Omoluabi T; Division of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador Canada., Torraville SE; Division of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador Canada., Maziar A; Division of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador Canada., Ghosh A; Division of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador Canada., Power KD; Division of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador Canada., Reinhardt C; Division of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador Canada., Harley CW; Department of Psychology, Faculty of Science Memorial University St. John's Newfoundland and Labrador Canada., Yuan Q; Division of Biomedical Sciences, Faculty of Medicine Memorial University St. John's Newfoundland and Labrador Canada.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (New York, N. Y.) [Alzheimers Dement (N Y)] 2021 Dec 31; Vol. 7 (1), pp. e12231. Date of Electronic Publication: 2021 Dec 31 (Print Publication: 2021).
DOI: 10.1002/trc2.12231
Abstrakt: 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.
Competing Interests: Qi Yuan has been appointed as a member of the Natural Sciences and Engineering Research Council of Canada (NSERC) Genes, Cells and Molecules Evaluation Group (Neuroscience) for a 3‐year term ending on the June 30, 2021. NSERC funds non–health‐related science and engineering research grants. This work was supported by Canadian Institute of Health Research project grant (#PJT‐16124) to Qi Yuan, received in April 2019 (5 years) and paid to Memorial University. All other authors have nothing to disclose.
(© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
Externí odkaz: