| First Author | Balducci C | Year | 2018 |
| Journal | Neurobiol Aging | Volume | 70 |
| Pages | 128-139 | PubMed ID | 30007162 |
| Mgi Jnum | J:266928 | Mgi Id | MGI:6257084 |
| Doi | 10.1016/j.neurobiolaging.2018.06.002 | Citation | Balducci C, et al. (2018) Doxycycline counteracts neuroinflammation restoring memory in Alzheimer's disease mouse models. Neurobiol Aging 70:128-139 |
| abstractText | beta-Amyloid oligomers (AbetaOs) and neuroinflammation are 2 main culprits to counteract in Alzheimer's disease (AD). Doxycycline (DOXY) is a second generation antibiotic of the tetracycline class that are promising drugs tested in many clinical trials for a number of different pathologies. DOXY is endowed with antiamyloidogenic properties and better crosses the blood-brain barrier, but its efficacy has never been tested in AD mice. We herein show that 15- to 16-month-old APP/PS1dE9 (APP/PS1) AD mice receiving DOXY under different treatment regimens recovered their memory without plaque reduction. An acute DOXY treatment was, also, sufficient to improve APP/PS1 mouse memory, suggesting an action against soluble AbetaOs. This was confirmed in an AbetaO-induced mouse model, where the AbetaO-mediated memory impairment was abolished by a DOXY pretreatment. Although AbetaOs induce memory impairment through glial activation, assessing the anti-inflammatory action of DOXY, we found that in both the AbetaO-treated and APP/PS1 mice, the memory recovery was associated with a lower neuroinflammation. Our data promote DOXY as a hopeful repositioned drug counteracting crucial neuropathological AD targets. |
