| First Author | Duncan MJ | Year | 2019 |
| Journal | Alzheimers Dement (N Y) | Volume | 5 |
| Pages | 70-80 | PubMed ID | 30859123 |
| Mgi Jnum | J:284808 | Mgi Id | MGI:6391682 |
| Doi | 10.1016/j.trci.2019.01.003 | Citation | Duncan MJ, et al. (2019) Effects of the dual orexin receptor antagonist DORA-22 on sleep in 5XFAD mice. Alzheimers Dement (N Y) 5:70-80 |
| abstractText | Introduction: Sleep disruption is a characteristic of Alzheimer's disease (AD) that may exacerbate disease progression. This study tested whether a dual orexin receptor antagonist (DORA) would enhance sleep and attenuate neuropathology, neuroinflammation, and cognitive deficits in an AD-relevant mouse model, 5XFAD. Methods: Wild-type (C57Bl6/SJL) and 5XFAD mice received chronic treatment with vehicle or DORA-22. Piezoelectric recordings monitored sleep and spatial memory was assessed via spontaneous Y-maze alternations. Abeta plaques, Abeta levels, and neuroinflammatory markers were measured by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction, respectively. Results: In 5XFAD mice, DORA-22 significantly increased light-phase sleep without reducing Abeta levels, plaque density, or neuroinflammation. Effects of DORA-22 on cognitive deficits could not be determined because the 5XFAD mice did not exhibit deficits. Discussion: These findings suggest that DORAs may improve sleep in AD patients. Further investigations should optimize the dose and duration of DORA-22 treatment and explore additional AD-relevant animal models and cognitive tests. |
