Author Correction: Inhibition of casein kinase 1δ/εimproves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer’s disease
| Autor: | H. Mahoney, C. Bloom, Danielle Gulick, A. Portugues, W. Li, Amara Yunus, Amy Henriksen, S. Azam, K. Millsaps, L. Pinto, M. Said, John Faulkner, S. K. Sundaram, M. Flores, S. Nagaraj, Joshua J. Gamsby, C. Burns |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-1 (2019) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-51830-5 |
| Popis: | Circadian rhythm disruption is one of the earliest biomarkers of Alzheimer's disease (AD), and there exists a bidirectional relationship by which dysfunctions in the circadian clock drive AD pathology and AD pathology drives circadian dysfunction. Casein kinase 1 (CK1) isoforms ε and δ, key circadian regulators, are significantly upregulated in AD and may contribute to AD pathogenesis. In the current studies, we have examined how inhibition of CK1ε/δ with PF-670462 (at 10 mg/kg, δ isoform selective, or 30 mg/kg, δ and ε selective) impacts regional Aβ and circadian gene expression in 10-13 month old APP-PS1 mice and nontransgenic controls. We have also assessed circadian, cognitive, and affective behavioral correlates of these neural changes. At baseline, APP-PS1 mice showed a short period, as well as impaired cognitive performance in both prefrontal cortex and hippocampus-dependent tasks. Both doses of PF-670462 lengthened the period and improved affect, whereas only the higher dose improved cognition. Further, PF-670462 treatment produced a dose-dependent reduction in amyloid burden - overall Aβ signal decreased in all three areas; in the prefrontal cortex and hippocampus, PF-670462 also reduced plaque size. Together, these findings support chronotherapy as a potential tool to improve behavior in AD. |
| Databáze: | OpenAIRE |
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